Research Article

Modeling human pregastrulation development by 3D culture of blastoids generated from primed-to-naïve transitioning intermediates

  • Zhifen Tu 1,2,3 ,
  • Yan Bi 1,2,3 ,
  • Xuehao Zhu 1,2 ,
  • Wenqiang Liu 2,3 ,
  • Jindian Hu 1,2,3 ,
  • Li Wu 2,3 ,
  • Tengyan Mao 1,2,3 ,
  • Jianfeng Zhou 1,2,3 ,
  • Hanwei Wang 1,2,3 ,
  • Hong Wang 1,2,3 ,
  • Shaorong Gao , 1,2,3 ,
  • Yixuan Wang , 1,3
Expand
  • 1. Translational Medical Center for Stem Cell Therapy & Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200120, China
  • 2. Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
  • 3. Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China
gaoshaorong@tongji.edu.cn
wangyixuan@tongji.edu.cn

Received date: 26 Jun 2022

Accepted date: 26 Aug 2022

Published date: 15 May 2023

Copyright

2022 The Author(s) 2022. Published by Oxford University Press on behalf of Higher Education Press.

Abstract

Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro. Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent stem cells or somatic reprogramming intermediates. However, whether blastoids can be generated from other cell types or whether they can recapitulate postimplantation development in vitro is unknown. Here, we develop a strategy to generate human blastoids from heterogeneous intermediates with epiblast, trophectoderm, and primitive endoderm signatures of the primed-to-naïve conversion process, which resemble natural blastocysts in morphological architecture, composition of cell lineages, transcriptome, and lineage differentiation potential. In addition, these blastoids reflect many features of human peri-implantation and pregastrulation development when further cultured in an in vitro 3D culture system. In summary, our study provides an alternative strategy to generate human blastoids and offers insights into human early embryogenesis by modeling peri- and postimplantation development in vitro.

Cite this article

Zhifen Tu , Yan Bi , Xuehao Zhu , Wenqiang Liu , Jindian Hu , Li Wu , Tengyan Mao , Jianfeng Zhou , Hanwei Wang , Hong Wang , Shaorong Gao , Yixuan Wang . Modeling human pregastrulation development by 3D culture of blastoids generated from primed-to-naïve transitioning intermediates[J]. Protein & Cell, 2023 , 14(5) : 337 -349 . DOI: 10.1093/procel/pwac041

1
Beccari L, Moris N, Girgin M et al. Multi-axial self-organization properties of mouse embryonic stem cells into gastruloids. Nature 2018;562:272–6.

DOI

2
Bedzhov I, Zernicka-Goetz M. Self-organizing properties of mouse pluripotent cells initiate morphogenesis upon implantation. Cell 2014;156:1032–44.

DOI

3
Bi Y, Tu Z, Zhang Y et al. Identification of ALPPL2 as a naive pluripotent state-specific surface protein essential for human naive pluripotency regulation. Cell Rep 2020;30:3917–3931.

DOI

4
Bi Y, Tu Z, Zhou J et al. Cell fate roadmap of human primed-to-naive transition reveals preimplantation cell lineage signatures. Nat Commun 2022;13:3147.

DOI

5
Deglincerti A, Croft GF, Pietila LN et al. Self-organization of the in vitro attached human embryo. Nature 2016;533:251–4.

DOI

6
Dong C, Beltcheva M, Gontarz P et al. Derivation of trophoblast stem cells from naive human pluripotent stem cells. Elife 2020;9:e52504.

DOI

7
Fan Y, Min Z, Alsolami S et al. Generation of human blastocyst-like structures from pluripotent stem cells. Cell Discov 2021;7:81.

DOI

8
Fu J, Warmflash A, Lutolf MP. Stem-cell-based embryo models for fundamental research and translation. Nat Mater 2021;20:132–44.

DOI

9
Harrison SE, Sozen B, Christodoulou N et al. Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro. Science 2017;356:eaal1810.

DOI

10
Kagawa H, Javali A, Khoei HH et al. Human blastoids model blastocyst development and implantation. Nature 2022;601:600–5.

DOI

11
Li R, Zhong C, Yu Y et al. Generation of blastocyst-like structures from mouse embryonic and adult cell cultures. Cell 2019;179:702.e18.e618.

DOI

12
Linneberg-Agerholm M, Wong YF, Romero Herrera JA et al. Naïve human pluripotent stem cells respond to Wnt, nodal and LIF signalling to produce expandable naïve extra-embryonic endoderm. Development 2019;146:dev180620.

DOI

13
Liu X, Tan JP, Schroder J et al. Modelling human blastocysts by reprogramming fibroblasts into iBlastoids. Nature 2021;591:627–32.

DOI

14
Mackinlay KM, Weatherbee BA, Souza Rosa V et al. An in vitro stem cell model of human epiblast and yolk sac interaction. Elife 2021;10:e63930.

DOI

15
Nakamura T, Okamoto I, Sasaki K et al. A developmental coordinate of pluripotency among mice, monkeys and humans. Nature 2016;537:57–62.

DOI

16
Okae H, Toh H, Sato T et al. Derivation of human trophoblast stem cells. Cell Stem Cell 2018;22:63.e6 e56.

DOI

17
Petropoulos S, Edsgard D, Reinius B et al. Single-cell RNA-Seq reveals lineage and X chromosome dynamics in human preimplantation embryos. Cell 2016;165:1012–26.

DOI

18
Rivron NC, Frias-Aldeguer J, Vrij EJ et al. Blastocyst-like structures generated solely from stem cells. Nature 2018;557:106–11.

DOI

19
Rossant J, Tam PPL. New insights into early human development: lessons for stem cell derivation and differentiation. Cell Stem Cell 2017;20:18–28.

DOI

20
Rossant J, Tam PPL. Opportunities and challenges with stem cell-based embryo models. Stem Cell Rep 2021;16:1031–8.

DOI

21
Shahbazi MN. Mechanisms of human embryo development: from cell fate to tissue shape and back. Development 2020;147:dev190629.

DOI

22
Shahbazi MN, Jedrusik A, Vuoristo S et al. Self-organization of the human embryo in the absence of maternal tissues. Nat Cell Biol 2016;18:700–8.

DOI

23
Shahbazi MN, Scialdone A, Skorupska N et al. Pluripotent state transitions coordinate morphogenesis in mouse and human embryos. Nature 2017;552:239–43.

DOI

24
Shahbazi MN, Zernicka-Goetz M. Deconstructing and reconstructing the mouse and human early embryo. Nat Cell Biol 2018;20:878–87.

DOI

25
Sozen B, Amadei G, Cox A et al. Self-assembly of embryonic and two extra-embryonic stem cell types into gastrulating embryo-like structures. Nat Cell Biol 2018;20:979–89.

DOI

26
Sozen B, Cox AL, De Jonghe J et al. Self-organization of mouse stem cells into an extended potential blastoid. Dev Cell 2019;51:712.e698.

DOI

27
Sozen B, Jorgensen V, Weatherbee BAT et al. Reconstructing aspects of human embryogenesis with pluripotent stem cells. Nat Commun 2021;12:5550.

DOI

28
Stuart T, Butler A, Hoffman P et al. Comprehensive integration of single-cell data. Cell 2019;177:1902.e21.e1821.

DOI

29
Theunissen TW, Powell BE, Wang H et al. Systematic identification of culture conditions for induction and maintenance of naive human pluripotency. Cell Stem Cell 2014;15:471–87.

DOI

30
Veenvliet JV, Bolondi A, Kretzmer H et al. Mouse embryonic stem cells self-organize into trunk-like structures with neural tube and somites. Science 2020;370:eaba4937.

DOI

31
Wu J, Izpisua Belmonte JC. Stem cells: a renaissance in human biology research. Cell 2016;165:1572–85.

DOI

32
Xiang L, Yin Y, Zheng Y et al. A developmental landscape of 3D-cultured human pre-gastrulation embryos. Nature 2020;577:537–42.

DOI

33
Yanagida A, Spindlow D, Nichols J et al. Naive stem cell blastocyst model captures human embryo lineage segregation. Cell Stem Cell 2021;28:1022.e4 e1014.

DOI

34
Yilmaz A, Benvenisty N. Defining human pluripotency. Cell Stem Cell 2019;25:9–22.

DOI

35
Yu J, Vodyanik MA, Smuga-Otto K et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 2007;318:1917–20.

DOI

36
Yu L, Wei Y, Duan J et al. Blastocyst-like structures generated from human pluripotent stem cells. Nature 2021;591:620–6.

DOI

37
Zhang S, Chen T, Chen N et al. Implantation initiation of self-assembled embryo-like structures generated using three types of mouse blastocyst-derived stem cells. Nat Commun 2019;10:496.

DOI

38
Zhao C, Reyes AP, Schell JP et al. Reprogrammed iBlastoids contain amnion-like cells but not trophectoderm. Biorxiv 2021.

DOI

Outlines

/