Differential impact of TGFβ/SMAD signalling activity elicited by Activin A and Nodal on endoderm differentiation of epiblast stem cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Genesis Année : 2022

Differential impact of TGFβ/SMAD signalling activity elicited by Activin A and Nodal on endoderm differentiation of epiblast stem cells

Hilary Knowles
Nazmus Salehin
Pierre Osteil

Résumé

Allocation of cells to an endodermal fate in the gastrulating embryo is driven by Nodal signalling and consequent activation of TGF pathway. In vitro methodologies striving to recapitulate the process of endoderm differentiation, however, used TGF family member Activin in place of Nodal. This is despite Activin not known to have an in vivo role in endoderm differentiation. In this study, five Epiblast Stem Cell lines were subjected to directed differentiation using both Activin A and Nodal to induce endodermal fate. A reporter line harbouring endoderm markers FoxA2 and Sox17 was further analysed for TGF pathway activation and WNT response. We demonstrated that Activin A treated cells remain more primitive streak-like when compared to Nodal treated cells that have a molecular profile suggestive of more advanced differentiation. Activin A elicited a robust TGF/SMAD activity, enhanced WNT signalling activity and promoted the generation of DE precursors. Nodal treatment resulted in lower TGF/SMAD activity, and a weaker, sustained WNT response, and ultimately failed to upregulate endoderm markers. This is despite signalling response resembling more closely the activity seen in vivo. These findings emphasise the importance of understanding the downstream activities of Activin A and Nodal signalling in directing in vitro endoderm differentiation of primedstate epiblast stem cells.
Fichier principal
Vignette du fichier
Knowles_author_version.pdf (100.81 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Licence : CC BY - Paternité

Dates et versions

hal-04454315 , version 1 (13-02-2024)

Identifiants

Citer

Hilary Knowles, Nicole Santucci, Joshua Studdert, Hwee Ngee Goh, Keren Kaufman-Francis, et al.. Differential impact of TGFβ/SMAD signalling activity elicited by Activin A and Nodal on endoderm differentiation of epiblast stem cells. Genesis, 2022, 60 (1-2), ⟨10.1002/dvg.23466⟩. ⟨hal-04454315⟩
1 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More