Primate gastrulation and early organogenesis at single-cell resolution.
Journal
Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
09
01
2022
accepted:
04
11
2022
pubmed:
15
12
2022
medline:
24
12
2022
entrez:
14
12
2022
Statut:
ppublish
Résumé
Our understanding of human early development is severely hampered by limited access to embryonic tissues. Due to their close evolutionary relationship with humans, nonhuman primates are often used as surrogates to understand human development but currently suffer from a lack of in vivo datasets, especially from gastrulation to early organogenesis during which the major embryonic cell types are dynamically specified. To fill this gap, we collected six Carnegie stage 8-11 cynomolgus monkey (Macaca fascicularis) embryos and performed in-depth transcriptomic analyses of 56,636 single cells. Our analyses show transcriptomic features of major perigastrulation cell types, which help shed light on morphogenetic events including primitive streak development, somitogenesis, gut tube formation, neural tube patterning and neural crest differentiation in primates. In addition, comparative analyses with mouse embryos and human embryoids uncovered conserved and divergent features of perigastrulation development across species-for example, species-specific dependency on Hippo signalling during presomitic mesoderm differentiation-and provide an initial assessment of relevant stem cell models of human early organogenesis. This comprehensive single-cell transcriptome atlas not only fills the knowledge gap in the nonhuman primate research field but also serves as an invaluable resource for understanding human embryogenesis and developmental disorders.
Identifiants
pubmed: 36517595
doi: 10.1038/s41586-022-05526-y
pii: 10.1038/s41586-022-05526-y
pmc: PMC9771819
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
732-738Subventions
Organisme : NICHD NIH HHS
ID : R01 HD103627
Pays : United States
Organisme : NICHD NIH HHS
ID : HD103627-01A1
Pays : United States
Informations de copyright
© 2022. The Author(s).
Références
O’Rahilly, R. & Müller, F. in "Horizons" and a Survey of the Carnegie Collection Section 1, 2–3 (Carnegie Institution of Washington, 1987).
Tyser, R. C. V. et al. Single-cell transcriptomic characterization of a gastrulating human embryo. Nature 600, 285–289 (2021).
doi: 10.1038/s41586-021-04158-y
Xu, Y. et al. A single-cell transcriptome atlas of human early embryogenesis. Preprint at bioRxiv https://doi.org/10.1101/2021.11.30.470583 (2021).
Nakamura, T. et al. A developmental coordinate of pluripotency among mice, monkeys and humans. Nature 537, 57–62 (2016).
doi: 10.1038/nature19096
Mittnenzweig, M. et al. A single-embryo, single-cell time-resolved model for mouse gastrulation. Cell 184, 2825–2842 (2021).
doi: 10.1016/j.cell.2021.04.004
Pijuan-Sala, B. et al. A single-cell molecular map of mouse gastrulation and early organogenesis. Nature 566, 490–495 (2019).
doi: 10.1038/s41586-019-0933-9
Chan, M. M. et al. Molecular recording of mammalian embryogenesis. Nature 570, 77–82 (2019).
doi: 10.1038/s41586-019-1184-5
La Manno, G. et al. RNA velocity of single cells. Nature 560, 494–498 (2018).
doi: 10.1038/s41586-018-0414-6
Scheibner, K. et al. Epithelial cell plasticity drives endoderm formation during gastrulation. Nat. Cell Biol. 23, 692–703 (2021).
doi: 10.1038/s41556-021-00694-x
Gilbert, S. F. & Barresi, M. J. F. Developmental Biology 12th edn (Sinauer Associates, 2019).
Bianchi, D. W., Wilkins-Haug, L. E., Enders, A. C. & Hay, E. D. Origin of extraembryonic mesoderm in experimental animals: relevance to chorionic mosaicism in humans. Am. J. Med. Genet. 46, 542–550 (1993).
doi: 10.1002/ajmg.1320460517
Ross, C. & Boroviak, T. E. Origin and function of the yolk sac in primate embryogenesis. Nat. Commun. 11, 3760 (2020).
doi: 10.1038/s41467-020-17575-w
Boss, A. L., Chamley, L. W. & James, J. L. Placental formation in early pregnancy: how is the centre of the placenta made? Hum. Reprod. Update 24, 750–760 (2018).
doi: 10.1093/humupd/dmy030
Cui, G. et al. Spatial and molecular anatomy of germ layers in the gastrulating cynomolgus monkey embryo. Cell Rep. 40, 111285 (2022).
Yoshioka-Kobayashi, K. et al. Coupling delay controls synchronized oscillation in the segmentation clock. Nature 580, 119–123 (2020).
doi: 10.1038/s41586-019-1882-z
Tani, S., Chung, U. I., Ohba, S. & Hojo, H. Understanding paraxial mesoderm development and sclerotome specification for skeletal repair. Exp. Mol. Med. 52, 1166–1177 (2020).
doi: 10.1038/s12276-020-0482-1
Nowotschin, S. et al. The emergent landscape of the mouse gut endoderm at single-cell resolution. Nature 569, 361–367 (2019).
doi: 10.1038/s41586-019-1127-1
Kimura-Yoshida, C. et al. Canonical Wnt signaling and its antagonist regulate anterior-posterior axis polarization by guiding cell migration in mouse visceral endoderm. Dev. Cell 9, 639–650 (2005).
doi: 10.1016/j.devcel.2005.09.011
Yamamoto, M. et al. Nodal antagonists regulate formation of the anteroposterior axis of the mouse embryo. Nature 428, 387–392 (2004).
doi: 10.1038/nature02418
Tam, P. P. & Loebel, D. A. Gene function in mouse embryogenesis: get set for gastrulation. Nat. Rev. Genet. 8, 368–381 (2007).
doi: 10.1038/nrg2084
Souilhol, C., Cormier, S., Tanigaki, K., Babinet, C. & Cohen-Tannoudji, M. RBP-Jkappa-dependent notch signaling is dispensable for mouse early embryonic development. Mol. Cell. Biol. 26, 4769–4774 (2006).
doi: 10.1128/MCB.00319-06
Copp, A. J., Greene, N. D. & Murdoch, J. N. The genetic basis of mammalian neurulation. Nat. Rev. Genet. 4, 784–793 (2003).
doi: 10.1038/nrg1181
Spemann, H. & Mangold, H. Induction of embryonic primordia by implantation of organizers from a different species. 1923. Int. J. Dev. Biol. 45, 13–38 (2001).
Barth, K. A. et al. Bmp activity establishes a gradient of positional information throughout the entire neural plate. Development 126, 4977–4987 (1999).
doi: 10.1242/dev.126.22.4977
Patthey, C., Edlund, T. & Gunhaga, L. Wnt-regulated temporal control of BMP exposure directs the choice between neural plate border and epidermal fate. Development 136, 73–83 (2009).
doi: 10.1242/dev.025890
Kiecker, C. & Lumsden, A. The role of organizers in patterning the nervous system. Annu. Rev. Neurosci. 35, 347–367 (2012).
doi: 10.1146/annurev-neuro-062111-150543
Martyn, I., Kanno, T. Y., Ruzo, A., Siggia, E. D. & Brivanlou, A. H. Self-organization of a human organizer by combined Wnt and Nodal signalling. Nature 558, 132–135 (2018).
doi: 10.1038/s41586-018-0150-y
Sauka-Spengler, T. & Bronner-Fraser, M. A gene regulatory network orchestrates neural crest formation. Nat. Rev. Mol. Cell Biol. 9, 557–568 (2008).
doi: 10.1038/nrm2428
Soldatov, R. et al. Spatiotemporal structure of cell fate decisions in murine neural crest. Science 364, eaas9536 (2019).
doi: 10.1126/science.aas9536
Nordstrom, U., Jessell, T. M. & Edlund, T. Progressive induction of caudal neural character by graded Wnt signaling. Nat. Neurosci. 5, 525–532 (2002).
doi: 10.1038/nn0602-854
Briscoe, J., Pierani, A., Jessell, T. M. & Ericson, J. A homeodomain protein code specifies progenitor cell identity and neuronal fate in the ventral neural tube. Cell 101, 435–445 (2000).
doi: 10.1016/S0092-8674(00)80853-3
Fuccillo, M., Joyner, A. L. & Fishell, G. Morphogen to mitogen: the multiple roles of Hedgehog signalling in vertebrate neural development. Nat. Rev. Neurosci. 7, 772–783 (2006).
doi: 10.1038/nrn1990
Stamataki, D., Ulloa, F., Tsoni, S. V., Mynett, A. & Briscoe, J. A gradient of Gli activity mediates graded Sonic Hedgehog signaling in the neural tube. Genes Dev. 19, 626–641 (2005).
doi: 10.1101/gad.325905
Lei, Q., Zelman, A. K., Kuang, E., Li, S. & Matise, M. P. Transduction of graded Hedgehog signaling by a combination of Gli2 and Gli3 activator functions in the developing spinal cord. Development 131, 3593–3604 (2004).
doi: 10.1242/dev.01230
Yamaguti, M., Cho, K. W. & Hashimoto, C. Xenopus hairy2b specifies anterior prechordal mesoderm identity within Spemann’s organizer. Dev. Dyn. 234, 102–113 (2005).
doi: 10.1002/dvdy.20523
El Yakoubi, W. et al. Hes4 controls proliferative properties of neural stem cells during retinal ontogenesis. Stem Cells 30, 2784–2795 (2012).
doi: 10.1002/stem.1231
Diaz-Cuadros, M. et al. In vitro characterization of the human segmentation clock. Nature 580, 113–118 (2020).
doi: 10.1038/s41586-019-1885-9
Matsuda, M. et al. Species-specific segmentation clock periods are due to differential biochemical reaction speeds. Science 369, 1450–1455 (2020).
doi: 10.1126/science.aba7668
Zheng, Y. et al. Controlled modelling of human epiblast and amnion development using stem cells. Nature 573, 421–425 (2019).
doi: 10.1038/s41586-019-1535-2
Shao, Y. et al. A pluripotent stem cell-based model for post-implantation human amniotic sac development. Nat. Commun. 8, 208 (2017).
doi: 10.1038/s41467-017-00236-w
Hofbauer, P. et al. Cardioids reveal self-organizing principles of human cardiogenesis. Cell 184, 3299–3317 (2021).
doi: 10.1016/j.cell.2021.04.034
Minn, K. T. et al. High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid cultures. eLife 9, e59445 (2020).
doi: 10.7554/eLife.59445
Minn, K. T., Dietmann, S., Waye, S. E., Morris, S. A. & Solnica-Krezel, L. Gene expression dynamics underlying cell fate emergence in 2D micropatterned human embryonic stem cell gastruloids. Stem Cell Rep. 16, 1210–1227 (2021).
doi: 10.1016/j.stemcr.2021.03.031
Drakhlis, L., Devadas, S. B. & Zweigerdt, R. Generation of heart-forming organoids from human pluripotent stem cells. Nat. Protoc. 16, 5652–5672 (2021).
doi: 10.1038/s41596-021-00629-8
Drakhlis, L. et al. Human heart-forming organoids recapitulate early heart and foregut development. Nat. Biotechnol. 39, 737–746 (2021).
doi: 10.1038/s41587-021-00815-9
Rifes, P. et al. Modeling neural tube development by differentiation of human embryonic stem cells in a microfluidic WNT gradient. Nat. Biotechnol. 38, 1265–1273 (2020).
doi: 10.1038/s41587-020-0525-0
Haremaki, T. et al. Self-organizing neuruloids model developmental aspects of Huntington’s disease in the ectodermal compartment. Nat. Biotechnol. 37, 1198–1208 (2019).
doi: 10.1038/s41587-019-0237-5
Karzbrun, E. et al. Human neural tube morphogenesis in vitro by geometric constraints. Nature 599, 268–272 (2021).
doi: 10.1038/s41586-021-04026-9
De Santis, R., Etoc, F., Rosado-Olivieri, E. A. & Brivanlou, A. H. Self-organization of human dorsal-ventral forebrain structures by light induced SHH. Nat. Commun. 12, 6768 (2021).
doi: 10.1038/s41467-021-26881-w
Sanaki-Matsumiya, M. et al. Periodic formation of epithelial somites from human pluripotent stem cells. Nat. Commun. 13, 2325 (2022).
doi: 10.1038/s41467-022-29967-1
Yamasaki, J. et al. Vitrification and transfer of cynomolgus monkey (Macaca fascicularis) embryos fertilized by intracytoplasmic sperm injection. Theriogenology 76, 33–38 (2011).
doi: 10.1016/j.theriogenology.2011.01.010
Zheng, G. X. et al. Massively parallel digital transcriptional profiling of single cells. Nat. Commun. 8, 14049 (2017).
doi: 10.1038/ncomms14049
Stuart, T. et al. Comprehensive integration of single-cell data. Cell 177, 1888–1902 (2019).
doi: 10.1016/j.cell.2019.05.031
Wolock, S. L., Lopez, R. & Klein, A. M. Scrublet: computational identification of cell doublets in single-cell transcriptomic data. Cell Syst. 8, 281–291 (2019).
doi: 10.1016/j.cels.2018.11.005
Yu, G., Wang, L. G., Han, Y. & He, Q. Y. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16, 284–287 (2012).
doi: 10.1089/omi.2011.0118
Qiu, X. et al. Reversed graph embedding resolves complex single-cell trajectories. Nat. Methods 14, 979–982 (2017).
doi: 10.1038/nmeth.4402
Bergen, V., Lange, M., Peidli, S., Wolf, F. A. & Theis, F. J. Generalizing RNA velocity to transient cell states through dynamical modeling. Nat. Biotechnol. 38, 1408–1414 (2020).
doi: 10.1038/s41587-020-0591-3
Barile, M. et al. Coordinated changes in gene expression kinetics underlie both mouse and human erythroid maturation. Genome Biol. 22, 197 (2021).
doi: 10.1186/s13059-021-02414-y
Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587 (2021).
doi: 10.1016/j.cell.2021.04.048
Wolf, F. A., Angerer, P. & Theis, F. J. SCANPY: large-scale single-cell gene expression data analysis. Genome Biol. 19, 15 (2018).
doi: 10.1186/s13059-017-1382-0
Jacomy, M., Venturini, T., Heymann, S. & Bastian, M. ForceAtlas2, a continuous graph layout algorithm for handy network visualization designed for the Gephi software. PLoS ONE 9, e98679 (2014).
doi: 10.1371/journal.pone.0098679
Haghverdi, L., Buttner, M., Wolf, F. A., Buettner, F. & Theis, F. J. Diffusion pseudotime robustly reconstructs lineage branching. Nat. Methods 13, 845–848 (2016).
doi: 10.1038/nmeth.3971
Van de Sande, B. et al. A scalable SCENIC workflow for single-cell gene regulatory network analysis. Nat. Protoc. 15, 2247–2276 (2020).
doi: 10.1038/s41596-020-0336-2
Efremova, M., Vento-Tormo, M., Teichmann, S. A. & Vento-Tormo, R. CellPhoneDB: inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes. Nat. Protoc. 15, 1484–1506 (2020).
doi: 10.1038/s41596-020-0292-x
Vento-Tormo, R. et al. Single-cell reconstruction of the early maternal-fetal interface in humans. Nature 563, 347–353 (2018).
doi: 10.1038/s41586-018-0698-6
Kiselev, V. Y., Yiu, A. & Hemberg, M. scmap: Projection of single-cell RNA-seq data across data sets. Nat. Methods 15, 359–362 (2018).
doi: 10.1038/nmeth.4644
Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005).
doi: 10.1073/pnas.0506580102
Wu, J. et al. Interspecies chimerism with mammalian pluripotent stem cells. Cell 168, 473–486 (2017).
doi: 10.1016/j.cell.2016.12.036
Wu, J. et al. An alternative pluripotent state confers interspecies chimaeric competency. Nature 521, 316–321 (2015).
doi: 10.1038/nature14413
Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012).
doi: 10.1038/nmeth.2019
Kreshuk, A. et al. Automated detection and segmentation of synaptic contacts in nearly isotropic serial electron microscopy images. PLoS ONE 6, e24899 (2011).
doi: 10.1371/journal.pone.0024899