Hoogland, S. H. A. & Marks, H. Developments in pluripotency: a new formative state. Cell Res. 31, 493–494 (2021).

PubMed  PubMed Central  Google Scholar 

Nichols, J. & Smith, A. Naive and primed pluripotent states. Cell Stem Cell 4, 487–492 (2009).

CAS  PubMed  Google Scholar 

Wei, Y. et al. Dissecting embryonic and extraembryonic lineage crosstalk with stem cell co-culture. Cell 186, 5859–5875.e24 (2023).

CAS  PubMed  PubMed Central  Google Scholar 

Liu, L. et al. Modeling post-implantation stages of human development into early organogenesis with stem-cell-derived peri-gastruloids. Cell 186, 3776–3792.e16 (2023).

CAS  PubMed  Google Scholar 

Chen, D. et al. Human primordial germ cells are specified from lineage-primed progenitors. Cell Rep. 29, 4568–4582.e5 (2019).

CAS  PubMed  PubMed Central  Google Scholar 

Kojima, Y. et al. Evolutionarily distinctive transcriptional and signaling programs drive human germ cell lineage specification from pluripotent stem cells. Cell Stem Cell 21, 517–532 (2017).

CAS  PubMed  Google Scholar 

Xiang, L. et al. A developmental landscape of 3D-cultured human pre-gastrulation embryos. Nature 577, 537–542 (2020).

CAS  PubMed  Google Scholar 

Tyser, R. C. V. et al. Single-cell transcriptomic characterization of a gastrulating human embryo. Nature 600, 285–289 (2021).

CAS  PubMed  PubMed Central  Google Scholar 

Mackinlay, K. M. et al. An in vitro stem cell model of human epiblast and yolk sac interaction. Elife 10, e63930 (2021).

Chen, L. et al. The nuclear receptor HNF4 drives a brush border gene program conserved across murine intestine, kidney, and embryonic yolk sac. Nat. Commun. 12, 2886 (2021).

CAS  PubMed  PubMed Central  Google Scholar 

Sun, S. et al. A transgene-free, human peri-gastrulation embryo model with trilaminar embryonic disc-, amnion- and yolk sac-like structures. bioRxiv https://doi.org/10.1101/2024.08.05.606556 (2024).

Consortium, E. P. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57–74 (2012).

Google Scholar 

Xia, W. et al. Resetting histone modifications during human parental-to-zygotic transition. Science 365, 353–360 (2019).

CAS  PubMed  Google Scholar 

Zhao, C. et al. A comprehensive human embryo reference tool using single-cell RNA-sequencing data. Nat. Methods 22, 193–206 (2024).

PubMed  PubMed Central  Google Scholar 

Theunissen, T. W. et al. Systematic identification of culture conditions for induction and maintenance of naive human pluripotency. Cell Stem Cell 15, 471–487 (2014).

CAS  PubMed  PubMed Central  Google Scholar 

Hu, Z. et al. Transient inhibition of mTOR in human pluripotent stem cells enables robust formation of mouse-human chimeric embryos. Sci. Adv. 6, eaaz0298 (2020).

CAS  PubMed  PubMed Central  Google Scholar 

Sperber, H. et al. The metabolome regulates the epigenetic landscape during naive-to-primed human embryonic stem cell transition. Nat. Cell Biol. 17, 1523–1535 (2015).

CAS  PubMed  PubMed Central  Google Scholar 

Irie, N. et al. SOX17 is a critical specifier of human primordial germ cell fate. Cell 160, 253–268 (2015).

CAS  PubMed  PubMed Central  Google Scholar 

Takashima, Y. et al. Resetting transcription factor control circuitry toward ground-state pluripotency in human. Cell 158, 1254–1269 (2014).

CAS  PubMed  PubMed Central  Google Scholar 

Yu, L. et al. Derivation of intermediate pluripotent stem cells amenable to primordial germ cell specification. Cell Stem Cell 28, 550–567.e12 (2021).

CAS  PubMed  Google Scholar 

Kinoshita, M. et al. Capture of mouse and human stem cells with features of formative pluripotency. Cell Stem Cell 28, 2180 (2021).

CAS  PubMed  PubMed Central  Google Scholar 

Rostovskaya, M., Andrews, S., Reik, W. & Rugg-Gunn, P. J. Amniogenesis occurs in two independent waves in primates. Cell Stem Cell 29, 744–759 (2022).

CAS  PubMed  PubMed Central  Google Scholar 

Kobayashi, M. et al. Expanding homogeneous culture of human primordial germ cell-like cells maintaining germline features without serum or feeder layers. Stem Cell Rep. 17, 507–521 (2022).

CAS  Google Scholar 

Zheng, Y. et al. Controlled modelling of human epiblast and amnion development using stem cells. Nature 573, 421–425 (2019).

CAS  PubMed  PubMed Central  Google Scholar 

Chal, J. & Pourquié, O. Making muscle: skeletal myogenesis in vivo and in vitro. Development 144, 2104–2122 (2017).

CAS  PubMed  Google Scholar 

Zhang, J. et al. Functional cardiac fibroblasts derived from human pluripotent stem cells via second heart field progenitors. Nat. Commun. 10, 2238 (2019).

PubMed  PubMed Central  Google Scholar 

Rito, T. et al. Timely TGFβ signalling inhibition induces notochord. Nature 637, 673–682 (2025).

CAS  PubMed  Google Scholar 

Pedroza, M. et al. Self-patterning of human stem cells into post-implantation lineages. Nature 622, 574–583 (2023).

CAS  PubMed  PubMed Central  Google Scholar 

Karvas, R. M. et al. 3D-cultured blastoids model human embryogenesis from pre-implantation to early gastrulation stages. Cell Stem Cell 30, 1148–1165.e47 (2023).

CAS  PubMed  Google Scholar 

Weatherbee, B. A. T. et al. Pluripotent stem cell-derived model of the post-implantation human embryo. Nature 622, 584–593 (2023).

CAS  PubMed  PubMed Central  Google Scholar 

Hislop, J. et al. Modelling post-implantation human development to yolk sac blood emergence. Nature 626, 367–376 (2023).

PubMed  PubMed Central  Google Scholar 

Pham, T. X. A. et al. Modeling human extraembryonic mesoderm cells using naive pluripotent stem cells. Cell Stem Cell 29, 1346–1365.e10 (2022).

CAS  PubMed  PubMed Central  Google Scholar 

Oldak, B. et al. Complete human day 14 post-implantation embryo models from naive ES cells. Nature 622, 562–573 (2023).

CAS  PubMed  PubMed Central  Google Scholar 

Kagawa, H. et al. Human blastoids model blastocyst development and implantation. Nature 601, 600–605 (2022).

CAS  PubMed  Google Scholar 

Liu, X. et al. Modelling human blastocysts by reprogramming fibroblasts into iBlastoids. Nature 591, 627–632 (2021).

CAS  PubMed  Google Scholar 

Yu, L. et al. Blastocyst-like structures generated from human pluripotent stem cells. Nature 591, 620–626 (2021).

CAS  PubMed  Google Scholar 

Fan, Y. et al. Generation of human blastocyst-like structures from pluripotent stem cells. Cell Discov. 7, 81 (2021).

CAS  PubMed  PubMed Central  Google Scholar 

Sozen, B. et al. Reconstructing aspects of human embryogenesis with pluripotent stem cells. Nat. Commun. 12, 5550 (2021).

PubMed  PubMed Central  Google Scholar 

Ai, Z. et al. Dissecting peri-implantation development using cultured human embryos and embryo-like assembloids. Cell Res. 33, 661–678 (2023).

PubMed  PubMed Central  Google Scholar 

Zhou, F. et al. Reconstituting the transcriptome and DNA methylome landscapes of human implantation. Nature 572, 660–664 (2019).

C