Modeling human extraembryonic mesoderm cells using naive pluripotent stem cells

被引：50

作者：

Pham, Thi Xuan Ai ^{[1
]}

Panda, Amitesh ^{[1
]}

Kagawa, Harunobu ^{[2
]}

To, San Kit ^{[1
]}

Ertekin, Cankat ^{[1
]}

Georgolopoulos, Grigorios ^{[1
,6
]}

van Knippenberg, Sam S. F. A. ^{[1
]}

Allsop, Ryan Nicolaas ^{[1
]}

Bruneau, Alexandre ^{[3
]}

Chui, Jonathan Sai-Hong ^{[1
]}

Vanheer, Lotte ^{[1
]}

Janiszewski, Adrian ^{[1
]}

Chappell, Joel ^{[1
,7
]}

Oberhuemer, Michael ^{[1
,8
]}

Tchinda, Raissa Songwa ^{[1
,9
]}

Talon, Irene ^{[1
]}

Khodeer, Sherif ^{[1
]}

Rossant, Janet ^{[4
]}

Lluis, Frederic ^{[1
]}

David, Laurent ^{[3
,5
]}

Rivron, Nicolas

Balaton, Bradley Philip ^{[1
]}

Pasque, Vincent ^{[1
]}

机构：

[1] KU Leuven Univ Leuven, Leuven Stem Cell Inst, Leuven Inst Single cell Om LISCO, Dept Dev & Regenerat, B-3000 Leuven, Belgium

[2] Inst Mol Biotechnol Austrian Acad Sci IMBA, Vienna Bioctr VBC, A-1030 Vienna, Austria

[3] Nantes Univ, CHU Nantes, Inserm, CR2TI,UMR 1064, F-44000 Nantes, France

[4] Hosp Sick Children, Program Dev & Stem Cell Biol, Toronto, ON M5V 0B1, Canada

[5] Nantes Univ, CHU Nantes, Inserm, CNRS,BioCore, F-44000 Nantes, France

[6] Genev Technol Oy, Tampere 33100, Finland

[7] Bit bio, Dorothy Hodgkin Bldg Babraham Res, Cambridge CB22 3FH, England

[8] Univ Vienna, Max Perutz Labs Vienna, Vienna Bioctr VBC, A-1030 Vienna, Austria

[9] Univ Toledo, Dept Biol Sci, Toledo, OH 43606 USA

来源：

CELL STEM CELL | 2022年 / 29卷 / 09期

基金：

欧洲研究理事会;

关键词：

SELF-ORGANIZATION; HUMAN EMBRYO; HUMAN OVA; DIFFERENTIATION; GASTRULATION; ALLOCATION; EXPRESSION; ORIGIN; ROLES; STATE;

D O I：

10.1016/j.stem.2022.08.001

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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

引用

页码：1346 / +

页数：31

共 115 条

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