In vitro generation of mouse morula-like cells.

GY118F MLCs STAT3 signaling blastocyst embryoids embryonic stem cells morula morula-like cells stembryos synthetic embryos

Journal

Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028

Informations de publication

Date de publication:
20 Nov 2023
Historique:
received: 26 08 2022
revised: 21 04 2023
accepted: 29 09 2023
medline: 23 11 2023
pubmed: 25 10 2023
entrez: 24 10 2023
Statut: ppublish

Résumé

Generating cells with the molecular and functional properties of embryo cells and with full developmental potential is an aim with fundamental biological significance. Here we report the in vitro generation of mouse transient morula-like cells (MLCs) via the manipulation of signaling pathways. MLCs are molecularly distinct from embryonic stem cells (ESCs) and cluster instead with embryo 8- to 16-cell stage cells. A single MLC can generate a blastoid, and the efficiency increases to 80% when 8-10 MLCs are used. MLCs make embryoids directly, efficiently, and within 4 days. Transcriptomic analysis shows that day 4-5 MLC-derived embryoids contain the cell types found in natural embryos at early gastrulation. Furthermore, MLCs introduced into morulae segregate into epiblast (EPI), primitive endoderm (PrE), and trophectoderm (TE) fates in blastocyst chimeras and have a molecular signature indistinguishable from that of host embryo cells. These findings represent the generation of cells that are molecularly and functionally similar to the precursors of the first three cell lineages of the embryo.

Identifiants

pubmed: 37875119
pii: S1534-5807(23)00519-1
doi: 10.1016/j.devcel.2023.09.013
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2510-2527.e7

Informations de copyright

Copyright © 2023 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests J.C.R.S., H.L., L.E.B., H.T.S., J.W., and M.G. have submitted a patent application (202210437013.X) related to this work (filed by Guangzhou National Laboratory).

Auteurs

Huanhuan Li (H)

Guangzhou National Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China; Bioland Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China. Electronic address: li_huanhuan@gzlab.ac.cn.

Litao Chang (L)

Guangzhou National Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China; Guangzhou Medical University, Panyu District, Guangzhou, Guangdong Province 511495, China.

Jinyi Wu (J)

Guangzhou National Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China; Guangzhou Medical University, Panyu District, Guangzhou, Guangdong Province 511495, China.

Jiahui Huang (J)

Guangzhou National Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China.

Wei Guan (W)

Guangzhou National Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China.

Lawrence E Bates (LE)

Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, Cambridge CB2 0AW, UK.

Hannah T Stuart (HT)

Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, Cambridge CB2 0AW, UK.

Mingyue Guo (M)

Bioland Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China; Guangzhou Medical University, Panyu District, Guangzhou, Guangdong Province 511495, China.

Pengfei Zhang (P)

Bioland Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China.

Boyan Huang (B)

Guangzhou National Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China; Bioland Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China.

Chuanxin Chen (C)

Guangzhou National Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China; Bioland Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China.

Man Zhang (M)

Guangzhou National Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China; Bioland Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China.

Jiekai Chen (J)

Bioland Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China; CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.

Mingwei Min (M)

Guangzhou National Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China; Bioland Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China.

Guangming Wu (G)

Guangzhou National Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China; Bioland Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China.

Andrew P Hutchins (AP)

Shenzhen Key Laboratory of Gene Regulation and Systems Biology, Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong Province 518055, China.

José C R Silva (JCR)

Guangzhou National Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China; Bioland Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong Province 510005, China. Electronic address: jose_silva@gzlab.ac.cn.

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