Multimodal characterization of murine gastruloid development.
cell states
embryoids
gastruloids
imaging
pluripotency
screening
symmetry breaking
Journal
Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472
Informations de publication
Date de publication:
01 06 2023
01 06 2023
Historique:
received:
22
02
2023
revised:
16
04
2023
accepted:
25
04
2023
medline:
5
6
2023
pubmed:
21
5
2023
entrez:
20
5
2023
Statut:
ppublish
Résumé
Gastruloids are 3D structures generated from pluripotent stem cells recapitulating fundamental principles of embryonic pattern formation. Using single-cell genomic analysis, we provide a resource mapping cell states and types during gastruloid development and compare them with the in vivo embryo. We developed a high-throughput handling and imaging pipeline to spatially monitor symmetry breaking during gastruloid development and report an early spatial variability in pluripotency determining a binary response to Wnt activation. Although cells in the gastruloid-core revert to pluripotency, peripheral cells become primitive streak-like. These two populations subsequently break radial symmetry and initiate axial elongation. By performing a compound screen, perturbing thousands of gastruloids, we derive a phenotypic landscape and infer networks of genetic interactions. Finally, using a dual Wnt modulation, we improve the formation of anterior structures in the existing gastruloid model. This work provides a resource to understand how gastruloids develop and generate complex patterns in vitro.
Identifiants
pubmed: 37209681
pii: S1934-5909(23)00170-4
doi: 10.1016/j.stem.2023.04.018
pmc: PMC10241222
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
867-884.e11Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests M.P.L. is an employee of Roche and has equity in Roche.
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