An organism-wide atlas of hormonal signaling based on the mouse lemur single-cell transcriptome.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
11 Mar 2024
Historique:
received: 16 08 2022
accepted: 07 02 2024
medline: 12 3 2024
pubmed: 12 3 2024
entrez: 12 3 2024
Statut: epublish

Résumé

Hormones mediate long-range cell communication and play vital roles in physiology, metabolism, and health. Traditionally, endocrinologists have focused on one hormone or organ system at a time. Yet, hormone signaling by its very nature connects cells of different organs and involves crosstalk of different hormones. Here, we leverage the organism-wide single cell transcriptional atlas of a non-human primate, the mouse lemur (Microcebus murinus), to systematically map source and target cells for 84 classes of hormones. This work uncovers previously-uncharacterized sites of hormone regulation, and shows that the hormonal signaling network is densely connected, decentralized, and rich in feedback loops. Evolutionary comparisons of hormonal genes and their expression patterns show that mouse lemur better models human hormonal signaling than mouse, at both the genomic and transcriptomic levels, and reveal primate-specific rewiring of hormone-producing/target cells. This work complements the scale and resolution of classical endocrine studies and sheds light on primate hormone regulation.

Identifiants

pubmed: 38467625
doi: 10.1038/s41467-024-46070-9
pii: 10.1038/s41467-024-46070-9
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2188

Subventions

Organisme : NIGMS NIH HHS
ID : R35 GM131792
Pays : United States

Investigateurs

Snigdha Agarwal (S)
Aditi Agrawal (A)
Ahmad Al-Moujahed (A)
Alina Alam (A)
Megan A Albertelli (MA)
Paul Allegakoen (P)
Thomas Ambrosi (T)
Jane Antony (J)
Steven Artandi (S)
Fabienne Aujard (F)
Ankit Baghel (A)
Isaac Bakerman (I)
Trygve E Bakken (TE)
Jalal Baruni (J)
Philip Beachy (P)
Biter Bilen (B)
Olga Botvinnik (O)
Scott D Boyd (SD)
Deviana Burhan (D)
Kerriann M Casey (KM)
Charles Chan (C)
Charles A Chang (CA)
Stephen Chang (S)
Ming Chen (M)
Michael F Clarke (MF)
Sheela Crasta (S)
Rebecca Culver (R)
Jessica D'Addabbo (J)
Spyros Darmanis (S)
Roozbeh Dehghannasiri (R)
Song-Lin Ding (SL)
Connor V Duffy (CV)
F Hernán Espinoza (FH)
Jean Farup (J)
Hannah K Frank (HK)
Margaret Fuller (M)
Astrid Gillich (A)
Elias Godoy (E)
Dita Gratzinger (D)
Lisbeth A Guethlein (LA)
Yan Hang (Y)
Kazuteru Hasegawa (K)
Rebecca D Hodge (RD)
Malachia Hoover (M)
Franklin W Huang (FW)
Kerwyn C Huang (KC)
Shelly Huynh (S)
Taichi Isobe (T)
Carly Israel (C)
SoRi Jang (S)
Qiuyu Jing (Q)
Robert C Jones (RC)
Jengmin Kang (J)
Caitlin J Karanewsky (CJ)
Jim Karkanias (J)
Justus Kebschull (J)
Aaron Kershner (A)
Lily Kim (L)
Seung K Kim (SK)
E Christopher Kirk (EC)
Winston Koh (W)
Silvana Konermann (S)
William Kong (W)
Corinne Lautier (C)
Song Eun Lee (SE)
Ed S Lein (ES)
Rebecca Lewis (R)
Peng Li (P)
Shengda Lin (S)
Yin Liu (Y)
Gabriel Loeb (G)
Wan-Jin Lu (WJ)
Katherine Lucot (K)
Liqun Luo (L)
Ashley Maynard (A)
Aaron McGeever (A)
Ross Metzger (R)
Jingsi Ming (J)
Tom Montine (T)
Antoine de Morree (A)
Maurizio Morri (M)
Karim Mrouj (K)
Shravani Mukherjee (S)
Ahmad Nabhan (A)
Saba Nafees (S)
Norma Neff (N)
Patrick Neuhöfer (P)
Patricia Nguyen (P)
Jennifer Okamoto (J)
Julia Olivieri (J)
Youcef Ouadah (Y)
Honor Paine (H)
Peter Parham (P)
Jozeph L Pendleton (JL)
Lolita Penland (L)
Martine Perret (M)
Angela Oliveira Pisco (AO)
Zhen Qi (Z)
Stephen R Quake (SR)
Ute Radespiel (U)
Thomas A Rando (TA)
Hajanirina Noëline Ravelonjanahary (H)
Andriamahery Razafindrakoto (A)
Julia Salzman (J)
Nicholas Schaum (N)
Robert Schopler (R)
Bronwyn Scott (B)
Liza Shapiro (L)
Hosu Sin (H)
Rahul Sinha (R)
Rene Sit (R)
Geoff Stanley (G)
Lubert Stryer (L)
Varun Ramanan Subramaniam (VR)
Aditi Swarup (A)
Michelle Tan (M)
Weilun Tan (W)
Alexander Tarashansky (A)
Aris Taychameekiatchai (A)
Kyle J Travaglini (KJ)
Andoni Urtasun (A)
None Sivakamasundari
Avin Veerakumar (A)
Venkata N P Vemuri (VNP)
Jean-Michel Verdier (JM)
Douglas Vollrath (D)
Bo Wang (B)
Bruce Wang (B)
Gefei Wang (G)
James Webber (J)
Hannah Weinstein (H)
Irving L Weissman (IL)
Amanda L Wiggenhorn (AL)
Cathy V Williams (CV)
Patricia Wright (P)
Albert Y Wu (AY)
Angela Ruohao Wu (AR)
Timothy Ting-Hsuan Wu (TT)
Tony Wyss-Coray (T)
BaoXiang Li (B)
Jia Yan (J)
Can Yang (C)
Jinxurong Yang (J)
Anne D Yoder (AD)
Brian Yu (B)
Andrea R Yung (AR)
Yue Zhang (Y)
Jia Zhao (J)
Zicheng Zhao (Z)

Informations de copyright

© 2024. The Author(s).

Références

Bayliss, W. M. & Starling, E. H. The mechanism of pancreatic secretion. J. Physiol. 28, 325–353 (1902).
pubmed: 16992627 pmcid: 1540572 doi: 10.1113/jphysiol.1902.sp000920
Takei, Y., Ando, H. & Tsutsui, K. Handbook of Hormones: Comparative Endocrinology for Basic and Clinical Research (Academic Press, 2015).
Tata, J. R. One hundred years of hormones. EMBO Rep. 6, 490–496 (2005).
pubmed: 15940278 pmcid: 1369102 doi: 10.1038/sj.embor.7400444
Lewis, G. F. & Brubaker, P. L. The discovery of insulin revisited: lessons for the modern era. J. Clin. Investig. 131, e142239 (2021).
pubmed: 33393501 pmcid: 7773348 doi: 10.1172/JCI142239
Horby, P. et al. Dexamethasone in hospitalized patients with Covid-19. New Engl. J. Med. 384, 693–704 (2021).
pubmed: 32678530 doi: 10.1056/NEJMoa2021436
Sterne, J. A. C. et al. Association Between administration of systemic corticosteroids and mortality among critically Ill patients with COVID-19: a meta-analysis. J. Am. Med. Assoc. 324, 1330–1341 (2020).
doi: 10.1001/jama.2020.17023
Scheja, L. & Heeren, J. The endocrine function of adipose tissues in health and cardiometabolic disease. Nat. Rev. Endocrinol. 15, 507–524 (2019).
pubmed: 31296970 doi: 10.1038/s41574-019-0230-6
Jabbour, H. N., Kelly, R. W., Fraser, H. M. & Critchley, H. O. D. Endocrine regulation of menstruation. Endocr. Rev. 27, 17–46 (2006).
pubmed: 16160098 doi: 10.1210/er.2004-0021
Deb, A., Deshmukh, B., Ramteke, P., Bhati, F. K. & Bhat, M. K. Resistin: a journey from metabolism to cancer. Transl. Oncol. 14, 101178 (2021).
pubmed: 34293684 pmcid: 8319804 doi: 10.1016/j.tranon.2021.101178
Ezran, C. et al. The mouse lemur, a genetic model organism for primate biology, behavior, and health. Genetics 206, 651–664 (2017).
pubmed: 28592502 pmcid: 5499178 doi: 10.1534/genetics.116.199448
Bons, N., Rieger, F., Prudhomme, D., Fisher, A. & Krause, K. H. Microcebus murinus: a useful primate model for human cerebral aging and Alzheimer’s disease? Genes Brain Behav. 5, 120–130 (2006).
pubmed: 16507003 doi: 10.1111/j.1601-183X.2005.00149.x
Languille, S. et al. The grey mouse lemur: a non-human primate model for ageing studies. Ageing Res. Rev. 11, 150–162 (2012).
pubmed: 21802530 doi: 10.1016/j.arr.2011.07.001
Kraska, A. et al. Age-associated cerebral atrophy in mouse lemur primates. Neurobiol. Aging 32, 894–906 (2011).
pubmed: 19564059 doi: 10.1016/j.neurobiolaging.2009.05.018
Pifferi, F. et al. Promoting healthspan and lifespan with caloric restriction in primates. Commun. Biol. 2, 107 (2019).
pubmed: 30911682 pmcid: 6420603 doi: 10.1038/s42003-019-0348-z
The Tabula Microcebus Consortium. Tabula Microcebus: a transcriptomic cell atlas of mouse lemur, an emerging primate model organism. Preprint at bioRxiv https://doi.org/10.1101/2021.12.12.469460 (2021).
The Tabula Microcebus Consortium et al. Mouse lemur transcriptomic atlas elucidates primate genes, physiology, disease, and evolution. Preprint at bioRxiv https://doi.org/10.1101/2022.08.06.503035 (2022).
Casey, K. M., Karanewsky, C. J., Pendleton, J. L., Krasnow, M. R. & Albertelli, M. A. Fibrous osteodystrophy, chronic renal disease, and uterine adenocarcinoma in aged gray mouse Lemurs (Microcebus murinus). Comp. Med. 71, 256–266 (2021).
pubmed: 34082858 pmcid: 8223869 doi: 10.30802/AALAS-CM-20-000078
Kastin, A. Handbook of Biologically Active Peptides (Academic Press, 2013).
Romere, C. et al. Asprosin, a fasting-induced glucogenic protein hormone. Cell 165, 566–579 (2016).
pubmed: 27087445 pmcid: 4852710 doi: 10.1016/j.cell.2016.02.063
Itoh, N., Ohta, H. & Konishi, M. Endocrine FGFs: evolution, physiology, pathophysiology, and pharmacotherapy. Front. Endocrinol. 6, 154 (2015).
doi: 10.3389/fendo.2015.00154
Hammond, G. L. Plasma steroid-binding proteins: primary gatekeepers of steroid hormone action. J. Endocrinol. 230, R13–R25 (2016).
pubmed: 27113851 pmcid: 5064763 doi: 10.1530/JOE-16-0070
Hammond, G. L., Hill, L. A. & Round, P. W. Roles of plasma binding proteins in modulation of hormone action and metabolism. In Encyclopedia of Endocrine Diseases, Second edition. (ed. Ilpo Huhtaniemi, L. M.) 51–60 (Academic Press, 2019).
Wang, M. F. Z. et al. Uncovering transcriptional dark matter via gene annotation independent single-cell RNA sequencing analysis. Nat. Commun. 12, 1–10 (2021).
Parfait, B. et al. Human TIP49b/RUVBL2 gene: genomic structure, expression pattern, physical link to the human CGB/LHB gene cluster on chromosome 19q13.3. Ann. Genet. 43, 69–74 (2000).
pubmed: 10998447 doi: 10.1016/S0003-3995(00)01016-9
Riddle, O., Bates, R. W. & Dykshorn, S. W. The preparation, identification and assay of prolactin—a hormone of the anterior pituitary. Am. J. Physiol.-Leg. Content 105, 191–216 (1933).
doi: 10.1152/ajplegacy.1933.105.1.191
Bole-Feysot, C., Goffin, V., Edery, M., Binart, N. & Kelly, P. A. Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr. Rev. 19, 225–268 (1998).
pubmed: 9626554 doi: 10.1210/edrv.19.3.0334
Tovar, S. & Diéguez, C. Prolactin and energy homeostasis: pathophysiological mechanisms and therapeutic considerations. Endocrinology 155, 659–662 (2014).
pubmed: 24564416 doi: 10.1210/en.2013-2167
Paré, P. et al. Molecular evolutionary insights from PRLR in mammals. Gen. Comp. Endocrinol. 309, 113791 (2021).
pubmed: 33872604 doi: 10.1016/j.ygcen.2021.113791
Giroud, S. et al. The grey mouse lemur uses season-dependent fat or protein sparing strategies to face chronic food restriction. PLoS ONE 5, e8823 (2010).
pubmed: 20098678 pmcid: 2809095 doi: 10.1371/journal.pone.0008823
Terrien, J. et al. Metabolic and genomic adaptations to winter fattening in a primate species, the grey mouse lemur (Microcebus murinus). Int. J. Obes. 42, 221–230 (2018).
doi: 10.1038/ijo.2017.195
Perret, M. & Aujard, F. Regulation by photoperiod of seasonal changes in body mass and reproductive function in gray mouse lemurs (Microcebus murinus): differential responses by sex. Int. J. Primatol. 22, 5–24 (2001).
doi: 10.1023/A:1026457813626
Maeda, K. et al. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). Biochem. Biophys. Res. Commun. 221, 286–289 (1996).
pubmed: 8619847 doi: 10.1006/bbrc.1996.0587
Zhang, Y. et al. Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432 (1994).
pubmed: 7984236 doi: 10.1038/372425a0
Galic, S., Oakhill, J. S. & Steinberg, G. R. Adipose tissue as an endocrine organ. Mol. Cell. Endocrinol. 316, 129–139 (2010).
pubmed: 19723556 doi: 10.1016/j.mce.2009.08.018
Ruan, H. & Dong, L. Q. Adiponectin signaling and function in insulin target tissues. J. Mol. Cell Biol. 8, 101–109 (2016).
pubmed: 26993044 pmcid: 4816150 doi: 10.1093/jmcb/mjw014
Yamauchi, T. et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423, 762–769 (2003).
pubmed: 12802337 doi: 10.1038/nature01705
He, J., Irwin, D. M., Chen, R. & Zhang, Y.-P. Stepwise loss of motilin and its specific receptor genes in rodents. J. Mol. Endocrinol. 44, 37–44 (2010).
pubmed: 19696113 doi: 10.1677/JME-09-0095
Sanger, G. J., Wang, Y., Hobson, A. & Broad, J. Motilin: towards a new understanding of the gastrointestinal neuropharmacology and therapeutic use of motilin receptor agonists. Br. J. Pharmacol. 170, 1323–1332 (2013).
pubmed: 23189978 pmcid: 3838679 doi: 10.1111/bph.12075
Hu, Q., Tan, H. & Irwin, D. M. Evolution of the vertebrate resistin gene family. PLoS One 10, e0130188 (2015).
pubmed: 26076481 pmcid: 4467842 doi: 10.1371/journal.pone.0130188
Schwartz, D. R. & Lazar, M. A. Human resistin: found in translation from mouse to man. Trends Endocrinol. Metab. 22, 259–265 (2011).
pubmed: 21497511 pmcid: 3130099
Zhang, X. et al. Neuropeptidomic analysis establishes a major role for prohormone convertase-2 in neuropeptide biosynthesis. J. Neurochem. 112, 1168–1179 (2010).
pubmed: 19968759 doi: 10.1111/j.1471-4159.2009.06530.x
Seidah, N. G. The proprotein convertases, 20 years later. Methods Mol. Biol. 768, 23–57 (2011).
pubmed: 21805237 doi: 10.1007/978-1-61779-204-5_3
Sandoval, D. A. & D’Alessio, D. A. Physiology of proglucagon peptides: role of glucagon and GLP-1 in health and disease. Physiol. Rev. 95, 513–548 (2015).
pubmed: 25834231 doi: 10.1152/physrev.00013.2014
Wardlaw, S. L. Hypothalamic proopiomelanocortin processing and the regulation of energy balance. Eur. J. Pharmacol. 660, 213–219 (2011).
pubmed: 21208604 pmcid: 3095770 doi: 10.1016/j.ejphar.2010.10.107
Allard, J. B. & Duan, C. IGF-binding proteins: why do they exist and why are there so many? Front. Endocrinol. 9, 117 (2018).
doi: 10.3389/fendo.2018.00117
Bouillon, R., Schuit, F., Antonio, L. & Rastinejad, F. Vitamin D binding protein: a historic overview. Front. Endocrinol. 10, 910 (2020).
doi: 10.3389/fendo.2019.00910
Schneider, C., O’Leary, C. E. & Locksley, R. M. Regulation of immune responses by tuft cells. Nat. Rev. Immunol. 19, 584–593 (2019).
pubmed: 31114038 pmcid: 8331098 doi: 10.1038/s41577-019-0176-x
Smith, B. et al. The OBO Foundry: coordinated evolution of ontologies to support biomedical data integration. Nat. Biotechnol. 25, 1251–1255 (2007).
pubmed: 17989687 pmcid: 2814061 doi: 10.1038/nbt1346
Wang, S. et al. Leveraging the cell ontology to classify unseen cell types. Nat. Commun. 12, 5556 (2021).
pubmed: 34548483 pmcid: 8455606 doi: 10.1038/s41467-021-25725-x
Griswold, M. D. Spermatogenesis: the commitment to meiosis. Physiol. Rev. 96, 1–17 (2016).
pubmed: 26537427 doi: 10.1152/physrev.00013.2015
Smith, L. B. & Walker, W. H. The regulation of spermatogenesis by androgens. Semin. Cell Dev. Biol. 30, 2–13 (2014).
pubmed: 24598768 doi: 10.1016/j.semcdb.2014.02.012
Ruwanpura, S. M., McLachlan, R. I. & Meachem, S. J. Hormonal regulation of male germ cell development. J. Endocrinol. 205, 117–131 (2010).
pubmed: 20144980 doi: 10.1677/JOE-10-0025
Lishko, P. V., Botchkina, I. L. & Kirichok, Y. Progesterone activates the principal Ca2+ channel of human sperm. Nature 471, 387–391 (2011).
pubmed: 21412339 doi: 10.1038/nature09767
Lue, Y. et al. Functional role of progestin and the progesterone receptor in the suppression of spermatogenesis in rodents. Andrology 1, 308–317 (2013).
pubmed: 23408752 doi: 10.1111/j.2047-2927.2012.00047.x
Burnicka-Turek, O. et al. Inactivation of insulin-like factor 6 disrupts the progression of spermatogenesis at late meiotic prophase. Endocrinology 150, 4348–4357 (2009).
pubmed: 19520787 doi: 10.1210/en.2009-0201
Giesecke, T. et al. Vasopressin increases urinary acidification via V1a receptors in collecting duct intercalated cells. J. Am. Soc. Nephrol. 30, 946–961 (2019).
pubmed: 31097611 pmcid: 6551786 doi: 10.1681/ASN.2018080816
Pannabecker, T. L. & Dantzler, W. H. Three-dimensional architecture of inner medullary vasa recta. Am. J. Physiol. Ren. Physiol. 290, F1355–F1366 (2006).
doi: 10.1152/ajprenal.00481.2005
Kenig-Kozlovsky, Y. et al. Ascending vasa recta are angiopoietin/tie2-dependent lymphatic-like vessels. J. Am. Soc. Nephrol. 29, 1097–1107 (2018).
pubmed: 29237738 doi: 10.1681/ASN.2017090962
Barry, D. M. et al. Molecular determinants of nephron vascular specialization in the kidney. Nat. Commun. 10, 5705 (2019).
pubmed: 31836710 pmcid: 6910926 doi: 10.1038/s41467-019-12872-5
Backes, F. J. et al. Estrogen receptor-alpha as a predictive biomarker in endometrioid endometrial cancer. Gynecol. Oncol. 141, 312–317 (2016).
pubmed: 26957478 pmcid: 4878441 doi: 10.1016/j.ygyno.2016.03.006
Shen, F., Gao, Y., Ding, J. & Chen, Q. Is the positivity of estrogen receptor or progesterone receptor different between type 1 and type 2 endometrial cancer? Oncotarget 8, 506–511 (2017).
pubmed: 27888807 doi: 10.18632/oncotarget.13471
Nakanishi, M. & Rosenberg, D. W. Multifaceted roles of PGE2 in inflammation and cancer. Semin. Immunopathol. 35, 123–137 (2013).
pubmed: 22996682 doi: 10.1007/s00281-012-0342-8
Ke, J. et al. Prostaglandin E2 (PGE2) promotes proliferation and invasion by enhancing SUMO-1 activity via EP4 receptor in endometrial cancer. Tumour Biol. 37, 12203–12211 (2016).
pubmed: 27230680 doi: 10.1007/s13277-016-5087-x
Lee, J. O. et al. Resistin, a fat-derived secretory factor, promotes metastasis of MDA-MB-231 human breast cancer cells through ERM activation. Sci. Rep. 6, 18923 (2016).
pubmed: 26729407 pmcid: 4700449 doi: 10.1038/srep18923
Groneberg, D. A., Springer, J. & Fischer, A. Vasoactive intestinal polypeptide as mediator of asthma. Pulm. Pharmacol. Ther. 14, 391–401 (2001).
pubmed: 11603952 doi: 10.1006/pupt.2001.0306
Barnes, K. & Turner, A. J. The endothelin system and endothelin-converting enzyme in the brain: molecular and cellular studies. Neurochem. Res. 22, 1033–1040 (1997).
pubmed: 9239759 doi: 10.1023/A:1022435111928
Wilhelms, D. B. et al. Deletion of prostaglandin E2 synthesizing enzymes in brain endothelial cells attenuates inflammatory fever. J. Neurosci. 34, 11684–11690 (2014).
pubmed: 25164664 pmcid: 6608410 doi: 10.1523/JNEUROSCI.1838-14.2014
Engström, L. et al. Lipopolysaccharide-induced fever depends on prostaglandin E2 production specifically in brain endothelial cells. Endocrinology 153, 4849–4861 (2012).
pubmed: 22872578 doi: 10.1210/en.2012-1375
Frankenstein, Z., Alon, U. & Cohen, I. R. The immune-body cytokine network defines a social architecture of cell interactions. Biol. Direct 1, 32 (2006).
pubmed: 17062134 pmcid: 1636025 doi: 10.1186/1745-6150-1-32
Giot, L. et al. A protein interaction map of Drosophila melanogaster. Science 302, 1727–1736 (2003).
pubmed: 14605208 doi: 10.1126/science.1090289
Yook, S. H., Oltvai, Z. N. & Barabási, A. L. Functional and topological characterization of protein interaction networks. Proteomics 4, 928–942 (2004).
pubmed: 15048975 doi: 10.1002/pmic.200300636
Rolland, T. et al. A proteome-scale map of the human interactome network. Cell 159, 1212–1226 (2014).
pubmed: 25416956 pmcid: 4266588 doi: 10.1016/j.cell.2014.10.050
Costanzo, M. et al. The genetic landscape of a cell. Science 327, 425–431 (2010).
pubmed: 20093466 pmcid: 5600254 doi: 10.1126/science.1180823
Barabási, A.-L. Scale-free and hierarchical structures in complex networks. AIP Conf. Proc. 661, 1–16 (2003).
doi: 10.1063/1.1571285
Iams, W. T. & Lovly, C. M. Molecular pathways: clinical applications and future direction of insulin-like growth factor-1 receptor pathway blockade. Clin. Cancer Res. 21, 4270–4277 (2015).
pubmed: 26429980 pmcid: 4593065 doi: 10.1158/1078-0432.CCR-14-2518
Ghosh, P., Dahms, N. M. & Kornfeld, S. Mannose 6-phosphate receptors: new twists in the tale. Nat. Rev. Mol. Cell Biol. 4, 202–212 (2003).
pubmed: 12612639 doi: 10.1038/nrm1050
Larhammar, D. & Salaneck, E. Molecular evolution of NPY receptor subtypes. Neuropeptides 38, 141–151 (2004).
pubmed: 15337367 doi: 10.1016/j.npep.2004.06.002
Kilpatrick, L. E., Humphrys, L. J. & Holliday, N. D. A G protein-coupled receptor dimer imaging assay reveals selectively modified pharmacology of neuropeptide Y Y1/Y5 receptor heterodimers. Mol. Pharmacol. 87, 718–732 (2015).
pubmed: 25637604 doi: 10.1124/mol.114.095356
Gehlert, D. R., Schober, D. A., Morin, M. & Berglund, M. M. Co-expression of neuropeptide Y Y1 and Y5 receptors results in heterodimerization and altered functional properties. Biochem. Pharmacol. 74, 1652–1664 (2007).
pubmed: 17897631 doi: 10.1016/j.bcp.2007.08.017
Almabouada, F. et al. Adiponectin receptors form homomers and heteromers exhibiting distinct ligand binding and intracellular signaling properties. J. Biol. Chem. 288, 3112–3125 (2013).
pubmed: 23255609 doi: 10.1074/jbc.M112.404624
Keshvari, S. et al. Characterisation of the adiponectin receptors: the non-conserved N-terminal region of AdipoR2 prevents its expression at the cell-surface. Biochem. Biophys. Res. Commun. 432, 28–33 (2013).
pubmed: 23376713 doi: 10.1016/j.bbrc.2013.01.092
Maslov, S. & Sneppen, K. Specificity and stability in topology of protein networks. Science 296, 910–913 (2002).
pubmed: 11988575 doi: 10.1126/science.1065103
Dwyer, A. A. & Quinton, R. Anatomy and physiology of the hypothalamic-pituitary-gonadal (HPG) axis. In Advanced Practice in Endocrinology Nursing (eds. Llahana, S. et al.). Springer, Cham. 839–852 (2019).
Martín-Estal, I., de la Garza, R. G. & Castilla-Cortázar, I. Intrauterine growth retardation (IUGR) as a novel condition of insulin-like growth factor-1 (IGF-1) deficiency. Rev. Physiol. Biochem. Pharmacol. 170, 1–35 (2016).
pubmed: 26634242 doi: 10.1007/112_2015_5001
Inagaki, T. et al. Inhibition of growth hormone signaling by the fasting-induced hormone FGF21. Cell Metab. 8, 77–83 (2008).
pubmed: 18585098 pmcid: 2575072 doi: 10.1016/j.cmet.2008.05.006
Hartig, S. M. & Cox, A. R. Paracrine signaling in islet function and survival. J. Mol. Med. 98, 451–467 (2020).
pubmed: 32067063 doi: 10.1007/s00109-020-01887-x
Habegger, K. M. et al. The metabolic actions of glucagon revisited. Nat. Rev. Endocrinol. 6, 689–697 (2010).
pubmed: 20957001 pmcid: 3563428 doi: 10.1038/nrendo.2010.187
Habegger, K. M. et al. Fibroblast growth factor 21 mediates specific glucagon actions. Diabetes 62, 1453–1463 (2013).
pubmed: 23305646 pmcid: 3636653 doi: 10.2337/db12-1116
Mu, J. et al. FGF21 analogs of sustained action enabled by orthogonal biosynthesis demonstrate enhanced antidiabetic pharmacology in rodents. Diabetes 61, 505–512 (2012).
pubmed: 22210323 pmcid: 3266413 doi: 10.2337/db11-0838
Mancuso, E. et al. Insulin-like growth factor-1 is a negative modulator of glucagon secretion. Oncotarget 8, 51719–51732 (2017).
pubmed: 28881681 pmcid: 5584282 doi: 10.18632/oncotarget.18514
Kopchick, J. J., Berryman, D. E., Puri, V., Lee, K. Y. & Jorgensen, J. O. L. The effects of growth hormone on adipose tissue: old observations, new mechanisms. Nat. Rev. Endocrinol. 16, 135–146 (2020).
pubmed: 31780780 doi: 10.1038/s41574-019-0280-9
Carré, N. & Binart, N. Prolactin and adipose tissue. Biochimie 97, 16–21 (2014).
pubmed: 24120689 doi: 10.1016/j.biochi.2013.09.023
Iwen, K. A. et al. Melanocortin crosstalk with adipose functions: ACTH directly induces insulin resistance, promotes a pro-inflammatory adipokine profile and stimulates UCP-1 in adipocytes. J. Endocrinol. 196, 465–472 (2008).
pubmed: 18310442 doi: 10.1677/JOE-07-0299
Sarmento-Cabral, A. et al. Adipokines (leptin, adiponectin, resistin) differentially regulate all hormonal cell types in primary anterior pituitary cell cultures from two primate species. Sci. Rep. 7, 43537 (2017).
pubmed: 28349931 pmcid: 5640086 doi: 10.1038/srep43537
Ferrell, J. E. Jr. Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability. Curr. Opin. Cell Biol. 14, 140–148 (2002).
pubmed: 11891111 doi: 10.1016/S0955-0674(02)00314-9
Tezze, C., Romanello, V. & Sandri, M. FGF21 as modulator of metabolism in health and disease. Front. Physiol. 10, 419 (2019).
pubmed: 31057418 pmcid: 6478891 doi: 10.3389/fphys.2019.00419
Kineman, R. D., Del Rio-Moreno, M. & Sarmento-Cabral, A. 40 Years of IGF1: understanding the tissue-specific roles of IGF1/IGF1R in regulating metabolism using the Cre/loxP. Syst. J. Mol. Endocrinol. 61, T187–T198 (2018).
doi: 10.1530/JME-18-0076
Petter-Rousseaux, A. Age of Microcebus murinus at the onset of testicular development: Preliminary observations on photoperiodic effect. Ann. Biol. Anim. Biochem. Biophys. 19, 1801–1806 (1979).
doi: 10.1051/rnd:19791015
Perret, M. Environmental and social determinants of sexual function in the male lesser mouse lemur (Microcebus murinus). Folia Primatol. 59, 1–25 (1992).
doi: 10.1159/000156637
Epelbaum, J. & Terrien, J. Mini-review: aging of the neuroendocrine system: Insights from nonhuman primate models. Prog. Neuropsychopharmacol. Biol. Psychiatry 100, 109854 (2020).
pubmed: 31891735 doi: 10.1016/j.pnpbp.2019.109854
Murat, F. et al. The molecular evolution of spermatogenesis across mammals. Nature 613, 308–316 (2023).
pubmed: 36544022 doi: 10.1038/s41586-022-05547-7
Champaneria, M. C., Modlin, I. M., Kidd, M. & Eick, G. N. Friedrich Feyrter: a precise intellect in a diffuse system. Neuroendocrinology 83, 394–404 (2006).
pubmed: 17028417 doi: 10.1159/000096050
Karin, O. et al. A new model for the HPA axis explains dysregulation of stress hormones on the timescale of weeks. Mol. Syst. Biol. 16, e9510 (2020).
pubmed: 32672906 pmcid: 7364861 doi: 10.15252/msb.20209510
Perret, M. & Aujard, F. Daily hypothermia and torpor in a tropical primate: synchronization by 24-h light-dark cycle. Am. J. Physiol.-Regul. Integr. Comp. Physiol. 281, R1925–R1933 (2001).
pubmed: 11705779 doi: 10.1152/ajpregu.2001.281.6.R1925
Gwinner, E. Circannual Rhythms: Endogenous Annual Clocks in the Organization of Seasonal Processes (Springer, 2011).
Lincoln, G. A brief history of circannual time. J. Neuroendocrinol. 31, e12694 (2019).
pubmed: 30739343 doi: 10.1111/jne.12694
Tendler, A. et al. Hormone seasonality in medical records suggests circannual endocrine circuits. Proc. Natl. Acad. Sci. USA 118, e2003926118 (2021).
pubmed: 33531344 pmcid: 7896322 doi: 10.1073/pnas.2003926118
Sailani, M. R. et al. Deep longitudinal multiomics profiling reveals two biological seasonal patterns in California. Nat. Commun. 11, 4933 (2020).
pubmed: 33004787 pmcid: 7529769 doi: 10.1038/s41467-020-18758-1
Dopico, X. C. et al. Widespread seasonal gene expression reveals annual differences in human immunity and physiology. Nat. Commun. 6, 7000 (2015).
pubmed: 25965853 doi: 10.1038/ncomms8000
Moriyama, M., Hugentobler, W. J. & Iwasaki, A. Seasonality of respiratory viral infections. Annu. Rev. Virol. 7, 83–101 (2020).
pubmed: 32196426 doi: 10.1146/annurev-virology-012420-022445
Marti-Soler, H. et al. Seasonal variation of overall and cardiovascular mortality: a study in 19 countries from different geographic locations. PLoS ONE 9, e113500 (2014).
pubmed: 25419711 pmcid: 4242652 doi: 10.1371/journal.pone.0113500
Kurlansik, S. L. & Ibay, A. D. Seasonal affective disorder. Am. Fam. Physician 86, 1037–1041 (2012).
Chen, G., Ning, B. & Shi, T. Single-cell RNA-Seq technologies and related computational data analysis. Front. Genet. 10, 317 (2019).
pubmed: 31024627 pmcid: 6460256 doi: 10.3389/fgene.2019.00317
Tabula Muris Consortium. A single-cell transcriptomic atlas characterizes ageing tissues in the mouse. Nature 583, 590–595 (2020).
doi: 10.1038/s41586-020-2496-1
The Tabula Muris Consortium Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris. Nature 562, 367–372 (2018).
doi: 10.1038/s41586-018-0590-4
Han, X. et al. Mapping the mouse cell atlas by Microwell-Seq. Cell 172, 1091–1107.e17 (2018).
pubmed: 29474909 doi: 10.1016/j.cell.2018.02.001
Cao, C. et al. Comprehensive single cell transcriptome lineages of a proto-vertebrate. Nature 571, 349–354 (2019).
pubmed: 31292549 pmcid: 6978789 doi: 10.1038/s41586-019-1385-y
Qu, J. et al. A reference single-cell regulomic and transcriptomic map of cynomolgus monkeys. Nat. Commun. 13, 4069 (2022).
pubmed: 35831300 pmcid: 9279386 doi: 10.1038/s41467-022-31770-x
Han, L. et al. Cell transcriptomic atlas of the non-human primate Macaca fascicularis. Nature 604, 723–731 (2022).
pubmed: 35418686 doi: 10.1038/s41586-022-04587-3
Tabula Sapiens Consortium* et al. The Tabula Sapiens: a multiple-organ, single-cell transcriptomic atlas of humans. Science 376, eabl4896 (2022).
van den Beld, A. W. et al. The physiology of endocrine systems with ageing. Lancet Diabetes Endocrinol. 6, 647–658 (2018).
pubmed: 30017799 pmcid: 6089223 doi: 10.1016/S2213-8587(18)30026-3
National Research Council. Guide for the Care and Use of Laboratory Animals, Eighth edition (National Research Council, 2010).
Chae, M., Danko, C. G. & Lee Kraus, W. groHMM: a computational tool for identifying unannotated and cell type-specific transcription units from global run-on sequencing data. BMC Bioinforma. 16, 1–16 (2015).
doi: 10.1186/s12859-015-0656-3
Johnson, M. et al. NCBI BLAST: a better web interface. Nucleic Acids Res. 36, W5–W9 (2008).
pubmed: 18440982 pmcid: 2447716 doi: 10.1093/nar/gkn201
Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. Basic local alignment search tool. J. Mol. Biol. 215, 403–410 (1990).
pubmed: 2231712 doi: 10.1016/S0022-2836(05)80360-2
Macosko, E. Z. et al. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161, 1202–1214 (2015).
pubmed: 26000488 pmcid: 4481139 doi: 10.1016/j.cell.2015.05.002
McInnes, L., Healy, J. & Melville, J. UMAP: Uniform Manifold Approximation and Projection. JOSS. 3, 29, 861 (2018).
doi: 10.21105/joss.00861
Meehan, C., Ebrahimian, J., Moore, W. & Meehan, S. Uniform manifold approximation and projection (UMAP). MATLAB Central File Exchange https://www.mathworks.com/matlabcentral/fileexchange/71902 (2021).
Reimers, N. & Gurevych, I. Sentence-BERT: sentence embeddings using Siamese BERT-Networks https://doi.org/10.48550/arXiv.1908.10084 (2019).
Butler, A., Hoffman, P., Smibert, P., Papalexi, E. & Satija, R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat. Biotechnol. 36, 411–420 (2018).
pubmed: 29608179 pmcid: 6700744 doi: 10.1038/nbt.4096
Clauset, A., Shalizi, C. R. & Newman, M. E. J. Power-law distributions in empirical data. SIAM Rev. Soc. Ind. Appl. Math. 51, 661–703 (2009).
Travaglini, K. J. et al. A molecular cell atlas of the human lung from single-cell RNA sequencing. Nature 587, 619–625 (2020).
pubmed: 33208946 pmcid: 7704697 doi: 10.1038/s41586-020-2922-4
Shami, A. N. et al. Single-cell RNA sequencing of human, macaque, and mouse testes uncovers conserved and divergent features of mammalian spermatogenesis. Dev. Cell 54, 529–547.e12 (2020).
pubmed: 32504559 pmcid: 7879256 doi: 10.1016/j.devcel.2020.05.010
Ernst, C., Eling, N., Martinez-Jimenez, C. P., Marioni, J. C. & Odom, D. T. Staged developmental mapping and X chromosome transcriptional dynamics during mouse spermatogenesis. Nat. Commun. 10, 1251 (2019).
pubmed: 30890697 pmcid: 6424977 doi: 10.1038/s41467-019-09182-1
Zhao, J. et al. Adversarial domain translation networks for integrating large-scale atlas-level single-cell datasets. Nat. Comput. Sci. 2, 317–330 (2022).
pubmed: 38177826 doi: 10.1038/s43588-022-00251-y
Fisher, R. A. Frequency distribution of the values of the correlation coefficient in samples from an indefinitely large population. Biometrika 10, 507–521 (1915).
Noiret, A. et al. Sex-specific response to caloric restriction after reproductive investment in Microcebus murinus: an integrative approach. Front. Physiol. 11, 506 (2020).
pubmed: 32612534 pmcid: 7308708 doi: 10.3389/fphys.2020.00506
Perret, M. & Aujard, F. Aging and season affect plasma dehydroepiandrosterone sulfate (DHEA-S) levels in a primate. Exp. Gerontol. 40, 582–587 (2005).
pubmed: 16019179 doi: 10.1016/j.exger.2005.05.002
Dal-Pan, A. et al. Caloric restriction or resveratrol supplementation and ageing in a non-human primate: first-year outcome of the RESTRIKAL study in Microcebus murinus. Age 33, 15–31 (2011).
pubmed: 20532988 doi: 10.1007/s11357-010-9156-6
Petter-Rousseaux, A. & Picon, R. Annual variation in the plasma testosterone in Microcebus murinus. Folia Primatol. 36, 183–190 (1981).
doi: 10.1159/000155994
Schilling, A. & Perret, M. Removal of the olfactory bulbs modifies the gonadal responses to photoperiod in the lesser mouse lemur (Microcebus murinus). Biol. Reprod. 49, 58–65 (1993).
pubmed: 8353190 doi: 10.1095/biolreprod49.1.58
Petter-Rousseaux, A. Annual variations in the plasma thyroxine level in Microcebus murinus. Gen. Comp. Endocrinol. 55, 405–409 (1984).
pubmed: 6468919 doi: 10.1016/0016-6480(84)90011-X
Perret, M. & Predine, J. Effects of long-term grouping on serum cortisol levels in Microcebus murinus (Prosimii). Horm. Behav. 18, 346–358 (1984).
pubmed: 6489945 doi: 10.1016/0018-506X(84)90021-7
Aujard, F., Bluet-Pajot, M. T., Zizzari, P., Perret, M. & Epelbaum, J. IGF-1: a marker of individual life-span in a primate. Ageing Res. 1, e2 (2010).
doi: 10.4081/ar.2010.e2
Aujard, F. et al. Artificially accelerated aging by shortened photoperiod alters early gene expression (Fos) in the suprachiasmatic nucleus and sulfatoxymelatonin excretion in a small primate, Microcebus murinus. Neuroscience 105, 403–412 (2001).
pubmed: 11672607 doi: 10.1016/S0306-4522(01)00202-0
Giroud, S. et al. Gut hormones in relation to body mass and torpor pattern changes during food restriction and re-feeding in the gray mouse lemur. J. Comp. Physiol. B 179, 99–111 (2009).
pubmed: 18726602 doi: 10.1007/s00360-008-0294-4
Dal-Pan, A., Blanc, S. & Aujard, F. Resveratrol suppresses body mass gain in a seasonal non-human primate model of obesity. BMC Physiol. 10, 11 (2010).
pubmed: 20569453 pmcid: 2903570 doi: 10.1186/1472-6793-10-11

Auteurs

Shixuan Liu (S)

Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.
Howard Hughes Medical Institute, Stanford, CA, USA.

Camille Ezran (C)

Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.
Howard Hughes Medical Institute, Stanford, CA, USA.

Michael F Z Wang (MFZ)

Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.

Zhengda Li (Z)

Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.

Kyle Awayan (K)

Chan Zuckerberg Biohub, San Francisco, CA, USA.

Jonathan Z Long (JZ)

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Sarafan ChEM-H, Stanford, CA, USA.

Iwijn De Vlaminck (I)

Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.

Sheng Wang (S)

Paul G. Allen School of Computer Science & Engineering, University of Washington, Seattle, WA, USA.

Jacques Epelbaum (J)

Adaptive Mechanisms and Evolution (MECADEV), UMR 7179, National Center for Scientific Research, National Museum of Natural History, Brunoy, France.

Christin S Kuo (CS)

Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.

Jérémy Terrien (J)

Adaptive Mechanisms and Evolution (MECADEV), UMR 7179, National Center for Scientific Research, National Museum of Natural History, Brunoy, France.

Mark A Krasnow (MA)

Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA. krasnow@stanford.edu.
Howard Hughes Medical Institute, Stanford, CA, USA. krasnow@stanford.edu.

James E Ferrell (JE)

Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA. james.ferrell@stanford.edu.
Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA. james.ferrell@stanford.edu.

Classifications MeSH