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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, DOI: 10.1016/j.devcel.2025.02.008 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Apical-basal Polarity ; Camp ; Multipotent Pancreatic Endocrine Progenitors ; Pancreas ; Pancreatic Alpha Cells ; Pancreatic Beta Cells
ISSN (print) / ISBN 1534-5807
e-ISSN 1878-1551
Zeitschrift Developmental Cell
Verlag Elsevier
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Transl. Stem Cell Research (ITS)