Titre
Morphogen-driven differentiation is precluded by physical confinement in human iPSCs spheroids.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Auteur(s)
Alsehli, H.S.
Auteure/Auteur
Roy, E.
Auteure/Auteur
Williams, T.
Auteure/Auteur
Kuziola, A.
Auteure/Auteur
Guo, Y.
Auteure/Auteur
Dreiss, C.A.
Auteure/Auteur
Green, JBA
Auteure/Auteur
Gentleman, E.
Auteure/Auteur
Danovi, D.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
2296-4185
Statut éditorial
Publié
Date de publication
2024
Volume
12
Première page
1467412
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
Cell lineage specification is tightly associated with profound morphological changes in the developing human embryo, particularly during gastrulation. The interplay between mechanical forces and biochemical signals is poorly understood.
Here, we dissect the effects of biochemical cues and physical confinement on a 3D in vitro model based on spheroids formed from human induced pluripotent stem cells (hiPSCs).
First, we compare self-renewing versus differentiating media conditions in free-floating cultures and observe the emergence of tri-germ layers. In these unconfined conditions, BMP4 exposure induces polarised expression of SOX17 in conjunction with spheroid elongation. We then physically confine spheroids using PEG-peptide hydrogels and observe dramatically reduced SOX17 expression, albeit rescued if gels that soften over time are used instead.
Our study combines high-content imaging, synthetic hydrogels, and hiPSCs-derived models of early development to define the drivers that cause changes in the shape and the emergence of germ layers.
Here, we dissect the effects of biochemical cues and physical confinement on a 3D in vitro model based on spheroids formed from human induced pluripotent stem cells (hiPSCs).
First, we compare self-renewing versus differentiating media conditions in free-floating cultures and observe the emergence of tri-germ layers. In these unconfined conditions, BMP4 exposure induces polarised expression of SOX17 in conjunction with spheroid elongation. We then physically confine spheroids using PEG-peptide hydrogels and observe dramatically reduced SOX17 expression, albeit rescued if gels that soften over time are used instead.
Our study combines high-content imaging, synthetic hydrogels, and hiPSCs-derived models of early development to define the drivers that cause changes in the shape and the emergence of germ layers.
PID Serval
serval:BIB_4788A37014EA
PMID
Open Access
Oui
Date de création
2024-11-12T09:05:07.296Z
Date de création dans IRIS
2025-05-20T13:42:19Z
Fichier(s)![Vignette d'image]()
En cours de chargement...
Nom
fbioe-12-1467412.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
2.82 MB
Format
Adobe PDF
PID Serval
serval:BIB_4788A37014EA.P001
URN
urn:nbn:ch:serval-BIB_4788A37014EA3
Somme de contrôle
(MD5):8d35428e353886f2eab18395fdb2e66a