Modeling human extraembryonic mesoderm cells using naive pluripotent stem cells DOI Creative Commons
Thi Xuan Ai Pham, Amitesh Panda, Harunobu Kagawa

et al.

Cell stem cell, Journal Year: 2022, Volume and Issue: 29(9), P. 1346 - 1365.e10

Published: Sept. 1, 2022

A hallmark of primate postimplantation embryogenesis is the specification extraembryonic mesoderm (EXM) before gastrulation, in contrast to rodents where this tissue formed only after gastrulation. Here, we discover that naive human pluripotent stem cells (hPSCs) are competent differentiate into EXM (EXMCs). EXMCs specified by inhibition Nodal signaling and GSK3B, maintained mTOR BMP4 activity, their transcriptome epigenome closely resemble monkey embryo EXM. mesenchymal, can arise from an epiblast intermediate, capable self-renewal. Thus, arising via primate-specific between implantation gastrulation be modeled vitro. We also find most rare off-target within blastoids triple (Kagawa et al., 2021) correspond EXMCs. Our study impacts our ability model molecular mechanisms early related defects.

Language: Английский

Spatial profiling of early primate gastrulation in utero DOI
Sophie Bergmann, Christopher A. Penfold, Erin Slatery

et al.

Nature, Journal Year: 2022, Volume and Issue: 609(7925), P. 136 - 143

Published: June 16, 2022

Language: Английский

Citations

97
Self-patterning of human stem cells into post-implantation lineages DOI Creative Commons

Monique Pedroza,

Seher Ipek Gassaloglu,

Nicolas Dias

et al.

Nature, Journal Year: 2023, Volume and Issue: 622(7983), P. 574 - 583

Published: June 27, 2023

Abstract Investigating human development is a substantial scientific challenge due to the technical and ethical limitations of working with embryonic samples. In face these difficulties, stem cells have provided an alternative experimentally model inaccessible stages in vitro 1–13 . Here we show that pluripotent can be triggered self-organize into three-dimensional structures recapitulate some key spatiotemporal events early post-implantation development. Our system reproducibly captures spontaneous differentiation co-development epiblast-like extra-embryonic hypoblast-like lineages, establishes signalling hubs secreted modulators undergoes symmetry breaking-like events. Single-cell transcriptomics confirms diverse cell states perigastrulating embryo 14,15 without establishing placental types, including signatures epiblast, amniotic ectoderm, primitive streak, mesoderm, endoderm, as well initial yolk sac induction. Collectively, our features spanning from Carnegie stage 16 4–7, offering reproducible, tractable scalable experimental platform understand basic cellular molecular mechanisms underlie development, new opportunities dissect congenital pathologies high throughput.

Language: Английский

Citations

92
Amniogenesis occurs in two independent waves in primates DOI Creative Commons
Maria Rostovskaya, Simon Andrews, Wolf Reik

et al.

Cell stem cell, Journal Year: 2022, Volume and Issue: 29(5), P. 744 - 759.e6

Published: April 18, 2022

In primates, the amnion emerges through cavitation of epiblast during implantation, whereas in other species it does so later at gastrulation by folding ectoderm. How mechanisms amniogenesis diversified evolution remains unknown. Unexpectedly, single-cell analysis primate embryos uncovered two transcriptionally and temporally distinct waves. To study this, we employed naive-to-primed transition human pluripotent stem cells (hPSCs) to model peri-implantation development. Partially primed hPSCs transiently gained ability differentiate into cavitating epithelium that morphologically matched early amnion, fully produced resembling late instead, thus recapitulating independent differentiation The wave follows a trophectoderm-like pathway encompasses cavitation, resembles an ectoderm-like route gastrulation. discovery waves explains how could emerge via duplication pre-existing trophectoderm program.

Language: Английский

Citations

76
3D-cultured blastoids model human embryogenesis from pre-implantation to early gastrulation stages DOI Creative Commons
Rowan M. Karvas, Joseph E. Zemke,

Syed Shahzaib Ali

et al.

Cell stem cell, Journal Year: 2023, Volume and Issue: 30(9), P. 1148 - 1165.e7

Published: Sept. 1, 2023

Naive human pluripotent stem cells have the remarkable ability to self-organize into blastocyst-like structures ("blastoids") that model lineage segregation in pre-implantation embryo. However, extent which blastoids can recapitulate defining features of post-implantation development remains unexplored. Here, we report cultured on thick three-dimensional (3D) extracellular matrices capture hallmarks early development, including epiblast lumenogenesis, rapid expansion and diversification trophoblast lineages, robust invasion extravillous by day 14. Extended blastoid culture results localized activation primitive streak marker TBXT emergence embryonic germ layers 21. We also show modulation WNT signaling alters balance between fates blastoids. This work demonstrates 3D-cultured offer a continuous integrated vitro system extraembryonic from gastrulation stages.

Language: Английский

Citations

57
Dissecting peri-implantation development using cultured human embryos and embryo-like assembloids DOI Creative Commons
Zongyong Ai, Ben Niu, Yu Yin

et al.

Cell Research, Journal Year: 2023, Volume and Issue: 33(9), P. 661 - 678

Published: July 17, 2023

Studies of cultured embryos have provided insights into human peri-implantation development. However, detailed knowledge lineage development as well underlying mechanisms remains obscure. Using 3D-cultured embryos, herein we report a complete cell atlas the early post-implantation lineages and decipher cellular composition gene signatures epiblast hypoblast derivatives. In addition, develop an embryo-like assembloid (E-assembloid) by assembling naive hESCs extraembryonic cells. E-assembloids, reveal that WNT, BMP Nodal signaling pathways synergistically, but functionally differently, orchestrate Specially, dissect mesoderm endoderm specifications. Finally, improved E-assembloid is developed to recapitulate tissue architectures in pre-gastrulation embryo. Our findings provide development, offers useful model disentangle behaviors interactions drive embryogenesis.

Language: Английский

Citations

49
Epigenetic regulation of early human embryo development DOI Creative Commons
Amy L. Wilkinson, Irene Zorzan, Peter J. Rugg‐Gunn

et al.

Cell stem cell, Journal Year: 2023, Volume and Issue: 30(12), P. 1569 - 1584

Published: Oct. 18, 2023

Studies of mammalian development have advanced our understanding the genetic, epigenetic, and cellular processes that orchestrate embryogenesis uncovered new insights into unique aspects human embryogenesis. Recent studies now produced first epigenetic maps early embryogenesis, stimulating ideas about reprogramming, cell fate control, potential mechanisms underpinning developmental plasticity in embryos. In this review, we discuss these regulation importance for safeguarding development. We also highlight unanswered questions key challenges remain to be addressed.

Language: Английский

Citations

45
Hallmarks of totipotent and pluripotent stem cell states DOI Creative Commons
Peng Du, Jun Wu

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(3), P. 312 - 333

Published: Feb. 20, 2024

Though totipotency and pluripotency are transient during early embryogenesis, they establish the foundation for development of all mammals. Studying these in vivo has been challenging due to limited access ethical constraints, particularly humans. Recent progress led diverse culture adaptations epiblast cells vitro form totipotent pluripotent stem cells, which not only deepen our understanding embryonic but also serve as invaluable resources animal reproduction regenerative medicine. This review delves into hallmarks shedding light on their key molecular functional features.

Language: Английский

Citations

30
Characterization of primary models of human trophoblast DOI Creative Commons
Megan A. Sheridan, Xiaohui Zhao,

Ridma C. Fernando

et al.

Development, Journal Year: 2021, Volume and Issue: 148(21)

Published: Oct. 15, 2021

ABSTRACT Two recently developed models, trophoblast organoids and stem cells (TSCs), are useful tools to further the understanding of human placental development. Both differentiate from villous cytotrophoblast (VCT) either extravillous (EVT) or syncytiotrophoblast (SCT). Here, we compare transcriptomes miRNA profiles these models identify which they resemble in vivo. Our findings indicate that TSCs do not readily undergo SCT differentiation closely at base cell columns where EVT derives. In contrast, similar VCT spontaneous differentiation. A defining feature is leukocyte antigen (HLA) null, whereas expresses HLA-C, -G -E molecules. We find retain vivo characteristics. express classical HLA-A HLA-B molecules, maintain their expression after differentiation, with upregulation HLA-G. Furthermore, HLA differs when grown 3D rather than 2D, suggesting mechanical cues important. results can be used select most suitable model for study development, function pathology.

Language: Английский

Citations

77
Opportunities and challenges with stem cell-based embryo models DOI Creative Commons
Janet Rossant, Patrick Tam

Stem Cell Reports, Journal Year: 2021, Volume and Issue: 16(5), P. 1031 - 1038

Published: March 7, 2021

Stem cell-based embryo models open an unprecedented avenue for modeling embryogenesis, cell lineage differentiation, tissue morphogenesis, and organogenesis in mammalian development. Experimentation on these can lead to a better understanding of the mechanisms development offers opportunities functional genomic studies disease-causing mechanisms, identification therapeutic targets, preclinical advanced therapeutics precision medicine. An immediate challenge is create high fidelity embryogenesis vivo, ensure that knowledge gleaned biologically meaningful clinically relevant.

Language: Английский

Citations

74
Human embryonic development: from peri-implantation to gastrulation DOI
Jinglei Zhai, Zhenyu Xiao, Yiming Wang

et al.

Trends in Cell Biology, Journal Year: 2021, Volume and Issue: 32(1), P. 18 - 29

Published: Aug. 17, 2021

Language: Английский

Citations

71