CD168 Identifies Proliferating Pancreatic Islet Cells in Murine and Human
Source abstract
Abstract
Abstract Restoring functional β‐cell mass through proliferation is a central goal of diabetes therapy, but progress has been hampered by the inability to isolate live, proliferating β‐cells for study. Here, CD168 is identified as a conserved surface marker that specifically enriches for proliferating cells in mouse and human pancreatic islets. Single‐cell RNA sequencing reveals a distinct cluster of islet cells with high proliferative activity, low insulin expression, and specific CD168 expression. Flow cytometry and immunostaining confirm CD168 + cells co‐localize with Ki67 + proliferating cells, reside in G2/M phase, and comprise ≈0.5% of adult islet cells. Using a new CD168‐CreERT2 mouse model for lineage tracing, it is demonstrated that CD168⁺ cells rapidly divide, forming two‐cell clones within hours. Unbiased lineage tracing shows 87.4% of clones are uni‐β lineage, with smaller proportions of uni‐α, uni‐δ, and multi‐lineage. Integrated lineage tracing with multi‐omics maps a ≈60‐day maturation trajectory for nascent β‐cells, involving progressive epigenome remodeling and shifting transcriptional networks. Notably, CD168 expression is conserved in proliferating cells of human islets and pancreatic neuroendocrine tumors, highlighting its clinical relevance. This work establishes CD168 as a marker for proliferating islet cells, providing a tool to study β‐cell proliferation and novel insights into islet cell proliferation and maturation mechanisms.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Pancreatic function and diabetes · Calcium signaling and nucleotide metabolism · Signaling Pathways in Disease
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
New Cornerstone Science Laboratory Key Laboratory of Multi‐Cell Systems Shanghai Institute of Biochemistry and Cell Biology Center for Excellence in Molecular Cell Science Chinese Academy of Sciences Shanghai 200031 China
University of Chinese Academy of Sciences Beijing 100049 China
Department of General Surgery Ruijin Hospital School of Medicine Shanghai Jiaotong University Shanghai 200025 China
Key Laboratory of Systems Health Science of Zhejiang Province School of Life Science Hangzhou Institute for Advanced Study Hangzhou 310024 China
Department of Hepatobiliary and Pancreatic Surgery of the Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310003 China
Department of Pancreatic Surgery Zhongshan Hospital Fudan University Shanghai 200032 China
Frontier Innovation Center Department of Immunology School of Basic Medical Sciences Fudan University Shanghai 200032 China
Department of Thoracic Surgery Shanghai Pulmonary Hospital Tongji University School of Medicine Shanghai 200433 China
Funding
National Key Research and Development Program of China · National Natural Science Foundation of China · Science and Technology Commission of Shanghai Municipality · CAS-Croucher Funding Scheme for Joint Laboratories
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