Hartman Institute for Therapeutic Organ Regeneration

Pre-existing beta cells but not progenitors contribute to new beta cells in the adult pancreas.

TitlePre-existing beta cells but not progenitors contribute to new beta cells in the adult pancreas.
Publication TypeJournal Article
Year of Publication2021
AuthorsZhao H, Huang X, Liu Z, Pu W, Lv Z, He L, Li Y, Zhou Q, Lui KO, Zhou B
JournalNat Metab
Volume3
Issue3
Pagination352-365
Date Published2021 Mar
ISSN2522-5812
KeywordsAging, Animals, Cell Differentiation, Cell Proliferation, Homeostasis, Insulin, Insulin-Secreting Cells, Mice, Pancreas
Abstract

<p>It has been suggested that new beta cells can arise from specific populations of adult pancreatic progenitors or facultative stem cells. However, their existence remains controversial, and the conditions under which they would contribute to new beta-cell formation are not clear. Here, we use a suite of mouse models enabling dual-recombinase-mediated genetic tracing to simultaneously fate map insulin-positive and insulin-negative cells in the adult pancreas. We find that the insulin-negative cells, of both endocrine and exocrine origin, do not generate new beta cells in the adult pancreas during homeostasis, pregnancy or injury, including partial pancreatectomy, pancreatic duct ligation or beta-cell ablation with streptozotocin. However, non-beta cells can give rise to insulin-positive cells after extreme genetic ablation of beta cells, consistent with transdifferentiation. Together, our data indicate that pancreatic endocrine and exocrine progenitor cells do not contribute to new beta-cell formation in the adult mouse pancreas under physiological conditions.</p>

DOI10.1038/s42255-021-00364-0
Alternate JournalNat Metab
PubMed ID33723463
PubMed Central IDPMC8628617
Grant ListR01 DK106253 / DK / NIDDK NIH HHS / United States
UC4 DK116280 / DK / NIDDK NIH HHS / United States

Weill Cornell Medicine
Hartman Institute for Therapeutic Organ Regeneration
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