Genetic recording of pancreatic beta cell proliferation

H Huan Zhao H Hui Chen Z Zhixin Kang (Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences) X Xiuzhen Huang (Chinese Academy of Sciences Center for Excellence in Molecuar Cell Science-Chinese University of Hong kong (CAS CEMCS-CUHK) Joint Laboratories, New Cornerstone Science Laboratory, State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences) J Jingting Zhu (Chinese Academy of Sciences Center for Excellence in Molecular Cell Science-The Chinese University of Hong Kong Joint Laboratories, New Cornerstone Science Laboratory, State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences) Z Zixin Liu (Tsinghua University , , ,) X Xiuxiu Liu (Chinese Academy of Sciences Center for Excellence in Molecular Cell Science-The Chinese University of Hong Kong Joint Laboratories, New Cornerstone Science Laboratory, State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences) X Ximeng Han (Chinese Academy of Sciences Center for Excellence in Molecular Cell Science-The Chinese University of Hong Kong Joint Laboratories, New Cornerstone Science Laboratory, State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences) J Jie Lu B Bin Zhou

Abstract

Pancreatic beta cell generation and proliferation primarily rely on the self renewal of preexisting beta cells, making precise quantification of beta cell proliferation essential for understanding pancreatic homeostasis and pathogenesis. However, previous methods had limitations and were unable to trace beta cell proliferation in vivo over extended periods. Here, we developed beta cell ProTracer, a genetic system that uses dual recombinase technology to enable continuous and cell type-specific recording of beta cell proliferation in mice. The beta cell ProTracer system allows for the quantification of the proliferation rate of adult pancreatic beta cells during homeostasis and in response to injury or drug treatment. Clonal analysis of the proliferated beta cell population reveals a uniform proliferative capacity among these cells. Our findings enhance the understanding of beta cell proliferation dynamics in homeostasis, repair, and regeneration.

Article Details

Volume / Issue Vol. 123, Issue 7
Published February 17, 2026
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (10)

H

Huan Zhao

H

Hui Chen

Z

Zhixin Kang

Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences

X

Xiuzhen Huang

Chinese Academy of Sciences Center for Excellence in Molecuar Cell Science-Chinese University of Hong kong (CAS CEMCS-CUHK) Joint Laboratories, New Cornerstone Science Laboratory, State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences

J

Jingting Zhu

Chinese Academy of Sciences Center for Excellence in Molecular Cell Science-The Chinese University of Hong Kong Joint Laboratories, New Cornerstone Science Laboratory, State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences

Z

Zixin Liu

Tsinghua University , , ,

X

Xiuxiu Liu

Chinese Academy of Sciences Center for Excellence in Molecular Cell Science-The Chinese University of Hong Kong Joint Laboratories, New Cornerstone Science Laboratory, State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences

X

Ximeng Han

Chinese Academy of Sciences Center for Excellence in Molecular Cell Science-The Chinese University of Hong Kong Joint Laboratories, New Cornerstone Science Laboratory, State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences

J

Jie Lu

B

Bin Zhou