The construction of a testis transcriptional cell atlas from embryo to adult reveals various somatic cells and their molecular roles.
Heterogeneity
Male infertility
Paracrine cell–cell communication
Single-cell RNA sequencing
Somatic cells
Weighted gene co-expression network analysis
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
27 Nov 2023
27 Nov 2023
Historique:
received:
25
06
2023
accepted:
13
11
2023
medline:
29
11
2023
pubmed:
28
11
2023
entrez:
28
11
2023
Statut:
epublish
Résumé
The testis is a complex organ that undergoes extensive developmental changes from the embryonic stage to adulthood. The development of germ cells, which give rise to spermatozoa, is tightly regulated by the surrounding somatic cells. To better understand the dynamics of these changes, we constructed a transcriptional cell atlas of the testis, integrating single-cell RNA sequencing data from over 26,000 cells across five developmental stages: fetal germ cells, infants, childhood, peri-puberty, and adults. We employed various analytical techniques, including clustering, cell type assignments, identification of differentially expressed genes, pseudotime analysis, weighted gene co-expression network analysis, and evaluation of paracrine cell-cell communication, to comprehensively analyze this transcriptional cell atlas of the testis. Our analysis revealed remarkable heterogeneity in both somatic and germ cell populations, with the highest diversity observed in Sertoli and Myoid somatic cells, as well as in spermatogonia, spermatocyte, and spermatid germ cells. We also identified key somatic cell genes, including RPL39, RPL10, RPL13A, FTH1, RPS2, and RPL18A, which were highly influential in the weighted gene co-expression network of the testis transcriptional cell atlas and have been previously implicated in male infertility. Additionally, our analysis of paracrine cell-cell communication supported specific ligand-receptor interactions involved in neuroactive, cAMP, and estrogen signaling pathways, which support the crucial role of somatic cells in regulating germ cell development. Overall, our transcriptional atlas provides a comprehensive view of the cell-to-cell heterogeneity in the testis and identifies key somatic cell genes and pathways that play a central role in male fertility across developmental stages.
Sections du résumé
BACKGROUND
BACKGROUND
The testis is a complex organ that undergoes extensive developmental changes from the embryonic stage to adulthood. The development of germ cells, which give rise to spermatozoa, is tightly regulated by the surrounding somatic cells.
METHODS
METHODS
To better understand the dynamics of these changes, we constructed a transcriptional cell atlas of the testis, integrating single-cell RNA sequencing data from over 26,000 cells across five developmental stages: fetal germ cells, infants, childhood, peri-puberty, and adults. We employed various analytical techniques, including clustering, cell type assignments, identification of differentially expressed genes, pseudotime analysis, weighted gene co-expression network analysis, and evaluation of paracrine cell-cell communication, to comprehensively analyze this transcriptional cell atlas of the testis.
RESULTS
RESULTS
Our analysis revealed remarkable heterogeneity in both somatic and germ cell populations, with the highest diversity observed in Sertoli and Myoid somatic cells, as well as in spermatogonia, spermatocyte, and spermatid germ cells. We also identified key somatic cell genes, including RPL39, RPL10, RPL13A, FTH1, RPS2, and RPL18A, which were highly influential in the weighted gene co-expression network of the testis transcriptional cell atlas and have been previously implicated in male infertility. Additionally, our analysis of paracrine cell-cell communication supported specific ligand-receptor interactions involved in neuroactive, cAMP, and estrogen signaling pathways, which support the crucial role of somatic cells in regulating germ cell development.
CONCLUSIONS
CONCLUSIONS
Overall, our transcriptional atlas provides a comprehensive view of the cell-to-cell heterogeneity in the testis and identifies key somatic cell genes and pathways that play a central role in male fertility across developmental stages.
Identifiants
pubmed: 38012716
doi: 10.1186/s12967-023-04722-2
pii: 10.1186/s12967-023-04722-2
pmc: PMC10680190
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
859Informations de copyright
© 2023. The Author(s).
Références
Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6852-7
pubmed: 17426145
Cell Res. 2018 Dec;28(12):1141-1157
pubmed: 30315278
BMC Bioinformatics. 2008 Dec 29;9:559
pubmed: 19114008
Nat Commun. 2020 Nov 10;11(1):5683
pubmed: 33173058
Cell Mol Life Sci. 2019 Jul;76(14):2681-2695
pubmed: 30980107
Sci Rep. 2019 Apr 23;9(1):6448
pubmed: 31015481
Biol Reprod. 2010 Jan;82(1):54-65
pubmed: 19684331
Development. 2020 Jul 13;147(13):
pubmed: 32554530
Curr Biol. 2017 May 22;27(10):1498-1505.e6
pubmed: 28502657
Methods Mol Biol. 2019;1935:141-153
pubmed: 30758825
Biosystems. 2015 Jan;127:67-72
pubmed: 25451770
Int J Mol Sci. 2021 Feb 18;22(4):
pubmed: 33670439
Front Immunol. 2019 Dec 16;10:2872
pubmed: 31921137
Poult Sci. 2021 Mar;100(3):100892
pubmed: 33516476
JAMA. 2011 Jul 27;306(4):410-9
pubmed: 21791690
Proc Natl Acad Sci U S A. 2016 Apr 26;113(17):E2352
pubmed: 27044112
Mol Med Rep. 2018 Jan;17(1):705-713
pubmed: 29115523
Lancet Diabetes Endocrinol. 2017 Jul;5(7):554-564
pubmed: 27395770
Spermatogenesis. 2012 Apr 1;2(2):79-87
pubmed: 22670217
Andrology. 2019 Nov;7(6):867-877
pubmed: 31002754
Sci Rep. 2020 Oct 8;10(1):16813
pubmed: 33033347
Endocrinology. 2014 Dec;155(12):4964-74
pubmed: 25181385
Trends Cell Biol. 2015 Apr;25(4):198-213
pubmed: 25540894
Physiol Rev. 2016 Jan;96(1):1-17
pubmed: 26537427
J Anim Sci Technol. 2022 Jul;64(4):654-670
pubmed: 35969700
Nat Med. 2008 Nov;14(11):1197-213
pubmed: 18989307
Int J Mol Sci. 2019 Oct 29;20(21):
pubmed: 31671745
Reprod Biol Endocrinol. 2017 Aug 15;15(1):65
pubmed: 28810916
PLoS One. 2016 Apr 05;11(4):e0152837
pubmed: 27046189
Biol Reprod. 2019 Sep 1;101(3):617-634
pubmed: 31077285
J Androl. 2012 Jul-Aug;33(4):578-84
pubmed: 22016347
Endocr Connect. 2018 Feb;7(2):R69-R87
pubmed: 29351905
Cell. 2019 Jun 13;177(7):1677-1679
pubmed: 31199914
Front Endocrinol (Lausanne). 2021 Jul 23;12:648141
pubmed: 34367061
Adv Exp Med Biol. 2017;1034:29-38
pubmed: 29256125
Genes (Basel). 2022 Jul 21;13(7):
pubmed: 35886074
Mol Hum Reprod. 2017 Feb 10;23(2):79-90
pubmed: 28093458
Fertil Steril. 2017 Jan;107(1):236-242
pubmed: 27842994
Cell Rep. 2019 Feb 5;26(6):1501-1517.e4
pubmed: 30726734
BMC Genomics. 2015 Mar 07;16:156
pubmed: 25879484
Reprod Biol Endocrinol. 2003 Jul 09;1:52
pubmed: 12904263
Reprod Biol Endocrinol. 2015 Feb 22;13:8
pubmed: 25890347
Brief Bioinform. 2018 Jul 20;19(4):575-592
pubmed: 28077403
J Assist Reprod Genet. 2020 Aug;37(8):2007-2017
pubmed: 32436047
Semin Cell Dev Biol. 2022 Jan;121:71-81
pubmed: 34119408
Mol Endocrinol. 1989 Oct;3(10):1569-78
pubmed: 2481814
J Lipid Res. 2015 Feb;56(2):342-57
pubmed: 25502770
Genome Biol. 2003;4(5):P3
pubmed: 12734009
Hum Reprod. 2018 Feb 1;33(2):258-269
pubmed: 29237021
RNA Biol. 2014;11(1):33-41
pubmed: 24452241
Sex Dev. 2022;16(5-6):388-403
pubmed: 35086109
J Assist Reprod Genet. 2015 Apr;32(4):615-23
pubmed: 25711835
Fertil Steril. 2002 Aug;78(2):298-306
pubmed: 12137866
J Biol Chem. 2019 Jul 19;294(29):11062-11086
pubmed: 31171722
Hum Genet. 2019 Feb;138(2):125-140
pubmed: 30656449
Nucleic Acids Res. 2013 Jan;41(Database issue):D991-5
pubmed: 23193258
Cell Stem Cell. 2018 Oct 4;23(4):599-614.e4
pubmed: 30174296
Sci Rep. 2021 Sep 27;11(1):19089
pubmed: 34580317
Proc Natl Acad Sci U S A. 2017 Sep 26;114(39):E8194-E8203
pubmed: 28894006
Dev Dyn. 2000 Mar;217(3):293-8
pubmed: 10741423
Hum Reprod. 2012 Jun;27(6):1556-67
pubmed: 22447625
Stem Cell Res. 2017 Dec;25:300-309
pubmed: 29239848
Genome Res. 2003 Nov;13(11):2498-504
pubmed: 14597658
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
Front Genet. 2022 Oct 24;13:1024805
pubmed: 36353105
Cell Rep. 2015 Aug 18;12(7):1107-19
pubmed: 26257171
Microsc Res Tech. 2009 Nov;72(11):787-95
pubmed: 19551717
Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):1829-34
pubmed: 26831079
Reproduction. 2014 Oct;148(4):417-27
pubmed: 25030892
Clin Epigenetics. 2018 Oct 29;10(1):134
pubmed: 30373665
Cell Stem Cell. 2017 Jun 1;20(6):858-873.e4
pubmed: 28457750
Cell Death Differ. 2018 Mar;25(4):749-766
pubmed: 29305586
Front Genet. 2021 Apr 30;12:610116
pubmed: 33995471
Biol Reprod. 2015 Jun;92(6):145
pubmed: 25855264
Circ Res. 2008 Nov 21;103(11):1204-19
pubmed: 19028920
Int J Mol Sci. 2023 Feb 01;24(3):
pubmed: 36769069
Reproduction. 2014 Feb 03;147(3):R65-74
pubmed: 24357661
BMC Med Genomics. 2022 Dec 5;15(1):252
pubmed: 36471356
Nat Biotechnol. 2014 Apr;32(4):381-386
pubmed: 24658644
Cell Rep. 2018 Nov 6;25(6):1650-1667.e8
pubmed: 30404016
Nat Cell Biol. 2013 May;15(5):502-10
pubmed: 23604320
PLoS One. 2013 Apr 24;8(4):e62313
pubmed: 23638035
Int J Mol Sci. 2023 Mar 10;24(6):
pubmed: 36982403
Front Cell Dev Biol. 2021 Jul 22;9:689624
pubmed: 34368137
Cell J. 2014 Feb 3;16(1):79-90
pubmed: 24518977
Front Endocrinol (Lausanne). 2019 Apr 16;10:224
pubmed: 31040821
Exp Mol Med. 2018 Aug 7;50(8):1-14
pubmed: 30089861
PLoS Genet. 2012 Jun;8(6):e1002701
pubmed: 22761579
iScience. 2021 Oct 30;24(12):103396
pubmed: 34825148
Int J Mol Sci. 2020 Jul 15;21(14):
pubmed: 32679860
Annu Rev Physiol. 2012;74:453-75
pubmed: 22017176
Stem Cells Int. 2016;2016:1741072
pubmed: 26635880
Cell. 2020 Jan 23;180(2):248-262.e21
pubmed: 31978344
Reproduction. 2012 Apr;143(4):513-22
pubmed: 22232743
Cell Stem Cell. 2020 Feb 6;26(2):262-276.e4
pubmed: 31928944
J Cell Mol Med. 2011 Mar;15(3):468-83
pubmed: 21155977
Front Vet Sci. 2022 Mar 28;9:845709
pubmed: 35419445
Biochem Biophys Res Commun. 1990 Nov 30;173(1):240-5
pubmed: 1701633
FASEB J. 2021 May;35(5):e21513
pubmed: 33811704
Asian J Androl. 2021 Jan-Feb;23(1):24-29
pubmed: 32655042
J Androl. 2012 Mar-Apr;33(2):277-86
pubmed: 21636736
Front Endocrinol (Lausanne). 2018 Jul 19;9:369
pubmed: 30072948
Semin Cell Dev Biol. 2022 Jan;121:2-9
pubmed: 34229950
Sci Adv. 2023 Aug 4;9(31):eabq3173
pubmed: 37540753
Physiol Rev. 2012 Apr;92(2):577-95
pubmed: 22535892
Biol Reprod. 2008 Feb;78(2):352-60
pubmed: 17928633
Dev Cell. 2022 May 9;57(9):1160-1176.e5
pubmed: 35504286
Cell Rep Med. 2021 Sep 09;2(9):100395
pubmed: 34622232
Nucleic Acids Res. 2020 Jun 4;48(10):e55
pubmed: 32196115
Biol Reprod. 1980 Jun;22(5):1233-43
pubmed: 7417656