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Tiemann, U.* ; Tian, C. ; Hermann, F.* ; Proks, M.* ; Skovgaard, E.* ; Kulik, I. ; Di, Y. ; Sedzinski, J.* ; Semb, H.

Pancreatic alpha and beta cell fate choice is directed by apical-basal polarity dynamics.

Dev. Cell 60, 1871-1883.e5 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
A central question in cell and developmental biology is how extracellular cues control the differentiation of multipotent progenitors in a dynamically changing niche. Here, we identify apical-basal polarity as the main regulator of the differentiation of multipotent pancreatic Neurogenin3+ endocrine progenitors (EPs) into the beta or alpha cell fates. We show that human EPs dynamically change their apical-basal polarity status. Whereas polarized EPs are predisposed to differentiate into beta cells rather than alpha cells, inhibiting apical-basal polarity selectively suppresses beta cell differentiation. Single-cell RNA sequencing and complementary mechanistic data demonstrate that apical-basal polarity in human EPs promotes beta cell specification via cyclic AMP (cAMP)/PKA-cAMP response element binding protein (CREB)-EGR1-mediated inhibition of ARX expression, while reduced cAMP levels in non-polarized human EPs maintain expression of ARX, leading to alpha cell differentiation. These findings identify the apical-basal polarity status of multipotent EPs as a critical epithelial feature that determines their fate into the alpha or beta cell lineages.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Apical-basal Polarity ; Camp ; Multipotent Pancreatic Endocrine Progenitors ; Pancreas ; Pancreatic Alpha Cells ; Pancreatic Beta Cells; In-vitro; Cadherin; Progenitors; Trophectoderm; Maintenance; Neurogenin3; Generation; Expression; Distinct; Lineage
ISSN (print) / ISBN 1534-5807
e-ISSN 1878-1551
Journal Developmental Cell
Quellenangaben Volume: 60, Issue: 13, Pages: 1871-1883.e5 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Transl. Stem Cell Research (ITS)
Grants Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW) at the University of Copenhagen (NNF )
Deutsche Forschungsgemeinschaft (DFG)
Helmholtz Zentrum Munchen
Novo Nordisk Foundation Center for Stem Cell Biology (DanStem) at the University of Copenhagen (NNF)
European Union