Open AccessPre-existing beta cells but not progenitors contribute to new beta cells in the adult pancreas
Author(s) -
Huan Zhao,
Xiuzhen Huang,
Zixin Liu,
Wenjuan Pu,
Zan Lv,
Lingjuan He,
Yan Li,
Qiao Zhou,
Kathy O. Lui,
Bin Zhou
Publication year - 2021
Publication title -
nature metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.834
H-Index - 22
ISSN - 2522-5812
DOI - 10.1038/s42255-021-00364-0
Subject(s) - beta (programming language) , pancreas , progenitor cell , beta cell , microbiology and biotechnology , biology , endocrinology , stem cell , computer science , diabetes mellitus , programming language , islet
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.