SSBD:database v3

379-Okubo-bilaminoid

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OMERO index

Project

Title

3D images of bilaminar organoid generated from co-culture of human pluripotent stem cells (hPSC) and hPSC-derived hypoblast-like cells

Description

Recently, several studies using cultures of human embryos together with single-cell RNA-seq analyses have revealed differences between humans and mice, necessitating the study of human embryos. Despite the importance of human embryology, ethical and legal restrictions have limited post-implantation-stage studies. Thus, recent efforts have focused on developing in vitro self-organizing models using human stem cells. In this paper, the authors report genetic and non-genetic approaches to generate authentic hypoblast cells (naive hPSC-derived hypoblast-like cells (nHyCs))-known to give rise to one of the two extraembryonic tissues essential for embryonic development-from naive human pluripotent stem cells (hPSCs). Their nHyCs spontaneously assemble with naive hPSCs to form a three-dimensional bilaminar structure (bilaminoids) with a pro-amniotic-like cavity. In the presence of additional naive hPSC-derived analogues of the second extraembryonic tissue, the trophectoderm, the efficiency of bilaminoid formation increases from 20% to 40%, and the epiblast within the bilaminoids continues to develop in response to trophectoderm-secreted IL-6. Furthermore, they show that bilaminoids robustly recapitulate the patterning of the anterior-posterior axis and the formation of cells reflecting the pregastrula stage, the emergence of which can be shaped by genetically manipulating the DKK1/OTX2 hypoblast-like domain.

License

CC BY

Released at

Oct. 20, 2025, midnight

Updated at

Funding

This work was supported by MEXT KAKENHI (grant numbers: JP16H02465, JP15H02360, JP20H05361, JP20H05762, JP21K19189, JP23K18340) and AMED (grant numbers: JP21bm0704035, JP21bm0104001, JP21gm1310011, JP23bm1323001) to Y.T.; MEXT KAKENHI (grant number: JP19H03418) and the JST FOREST Program (grant number: JPMJFR206C), JST CREST (grant number: JPMJCR2023) and AMED (grant numbers: JP17gm1110004, JP19gm1310002, JP19bm0704032, JP21bm0104001, JP21gm1310011) to T.Y.; MEXT KAKENHI (grant numbers: JP15H02360, JP19H05759) to E.S.; AMED (grant number: JP22bm1004002) to H.N.; the Takeda Science Foundation to Y.T.; the Naito Foundation to Y.T.; the Mochida Memorial Foundation for Medical and Pharmaceutical Research to Y.T.; and the Astellas Foundation for Research on Metabolic Disorders to Y.T.

# of image datasets

8

Papers

Papers

Paper information: Okubo T, Rivron N, Kabata M, Masaki H, Kishimoto K, Semi K, Nakajima-Koyama M, Kunitomi H, Kaswandy B, Sato H, Nakauchi H, Woltjen K, Saitou M, Sasaki E, Yamamoto T, Takashima Y. Hypoblast from human pluripotent stem cells regulates epiblast development. Nature. 2024 Feb;626(7998):357-366.,
Pubmed ID: 38052228,
PMCID: PMC10849967,
DOI: https://doi.org/10.1038/s41586-023-06871-2,
URL: https://pubmed.ncbi.nlm.nih.gov/38052228/

Contacts

Contacts

Takuya Yamamoto (Contact) , Center for iPS Cell Research and Application , Kyoto University
Yasuhiro Takashima (Contact) , Center for iPS Cell Research and Application , Kyoto University
Takumi Okubo (Imaging Contributor) , Center for iPS Cell Research and Application , Kyoto University

Biosamples

Organisms

Homo sapiens (NCBI:txid9606)

Strains

Cells

pluripotent stem cell (CL_0002248)

Cell lines

Ontologies

UBERON

pluripotent stem cell (CL_0002248)