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Tian, C. ; Rump, A. ; Ebeid, C.* ; Mamidi, A.* ; Semb, H.

Salt-inducible kinases transduce mechanical forces into the specification of the pancreatic endocrine lineage.

Stem Cell Rep. 20:102444 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The extracellular matrix-F-actin-Yes-associated protein 1 (YAP1)-Notch mechanosignaling axis is a gatekeeper in the fate decisions of bipotent pancreatic progenitors (bi-PPs). However, the link between F-actin dynamics and YAP1 activity remains poorly understood. Here, we identify salt-inducible kinases (SIKs) as mediators of F-actin-triggered changes in YAP1 activity. Interestingly, sodium chloride treatment promotes the differentiation of bi-PPs into NEUROG3+ endocrine progenitors (EPs) through enhanced SIK expression. Consistently, the pan-SIK inhibitor HG-9-09-01 (HG) inhibits latrunculin B (LatB)-induced EP differentiation via nuclear YAP1 accumulation. Unexpectedly, withdrawal of HG after a 12-h treatment increased SIK expression by a negative feedback mechanism, leading to significantly enhanced endocrinogenesis. Therefore, the combined treatment of bi-PPs with LatB and HG for 12 h boosted endocrinogenesis, ultimately leading to an increased number of beta cells. In summary, we identify SIKs as new transducers of mechanotransduction-triggered induction of pancreatic endocrine cell fates.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Yap1 ; Beta Cell ; Bipotent Pancreatic Progenitors ; Endocrine Progenitors ; Mechanotransduction ; Salt-inducible Kinases; Beta-cells; Generation
ISSN (print) / ISBN 2213-6711
Zeitschrift Stem Cell Reports
Quellenangaben Band: 20, Heft: 4, Seiten: , Artikelnummer: 102444 Supplement: ,
Verlag Elsevier
Verlagsort Maryland Heights, MO
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Transl. Stem Cell Research (ITS)
Förderungen Helmholtz Zentrum Munchen
Novo Nordisk Foundation Center for Stem Cell Biology (DanStem) at the University of Copenhagen (NNF)
European Union