Self-renewing human naïve pluripotent stem cells dedifferentiate in 3D culture and form blastoids spontaneously

Mingyue Guo (), Jinyi Wu, Chuanxin Chen, Xinggu Wang, An Gong, Wei Guan, Rowan M. Karvas, Kexin Wang, Mingwei Min, Yixuan Wang, Thorold W. Theunissen, Shaorong Gao and José C. R. Silva ()
Additional contact information
Mingyue Guo: Guangzhou Medical University
Jinyi Wu: Guangzhou Medical University
Chuanxin Chen: Guangzhou Medical University
Xinggu Wang: Guangzhou National Laboratory, Guangzhou International Bio Island
An Gong: Guangzhou Medical University
Wei Guan: Guangzhou Medical University
Rowan M. Karvas: Washington University School of Medicine
Kexin Wang: Guangzhou National Laboratory, Guangzhou International Bio Island
Mingwei Min: Guangzhou Medical University
Yixuan Wang: Tongji University
Thorold W. Theunissen: Washington University School of Medicine
Shaorong Gao: Tongji University
José C. R. Silva: Guangzhou National Laboratory, Guangzhou International Bio Island

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Human naïve pluripotent stem cells (hnPSCs) can generate integrated models of blastocysts termed blastoids upon switch to inductive medium. However, the underlying mechanisms remain obscure. Here we report that self-renewing hnPSCs spontaneously and efficiently give rise to blastoids upon three dimensional (3D) suspension culture. The spontaneous blastoids mimic early stage human blastocysts in terms of structure, size, and transcriptome characteristics and are capable of progressing to post-implantation stages. This property is conferred by the glycogen synthase kinase-3 (GSK3) signalling inhibitor IM-12 present in 5iLAF self-renewing medium. IM-12 upregulates oxidative phosphorylation-associated genes that underly the capacity of hnPSCs to generate blastoids spontaneously. Starting from day one of self-organization, hnPSCs at the boundary of all 3D aggregates dedifferentiate into E5 embryo-like intermediates. Intermediates co-express SOX2/OCT4 and GATA6 and by day 3 specify trophoblast fate, which coincides with cavity and blastoid formation. In summary, spontaneous blastoid formation results from 3D culture triggering dedifferentiation of hnPSCs into earlier embryo-like intermediates which are then competent to segregate blastocyst fates.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-024-44969-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44969-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-44969-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().