Accession PRJCA011718
Title Self-renewing human naive pluripotent stem cells dedifferentiate in 3D culture and form blastoids spontaneously
Relevance Other
Data types Transcriptome or Gene expression
Single cell sequencing
Organisms Homo sapiens
Description Human naive 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.
Sample scope Single cell
Release date 2023-12-28
Grants
Agency program Grant ID Grant title
Other 2022M712208
National Natural Science Foundation of China (NSFC) Young Scientists Fund 32200586
Accessions in other database
Accession Database name
GSE252114 NCBI
Submitter JOSE CARLOS REBELO DA SILVA (jose_silva@gzlab.ac.cn)
Organization Guangzhou Laboratory
Submission date 2022-09-06

Project Data

Resource name Description
BioSample (165)  show -