Rare, Tightly-Bound, Multi-Cellular Clusters in the Pancreatic Ducts of Adult Mice Function Like Progenitor Cells and Survive and Proliferate After Acinar Cell Injury

Author:

Tremblay Jacob R12,Ortiz Jose A12,Quijano Janine C1,Zook Heather N12ORCID,Erdem Neslihan12ORCID,LeBon Jeanne M1,Li Wendong1,Jou Kevin1,Tsark Walter3,Mann Jeffrey R3,Kozlowski Mark T4,Tirrell David A4,Esni Farzad5,Engle Dannielle D6,Riggs Arthur D1ORCID,Ku Hsun Teresa12ORCID

Affiliation:

1. Department of Translational Research and Cellular Therapeutics, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope , Duarte, CA , USA

2. The Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute, City of Hope , Duarte, CA , USA

3. Center for Comparative Medicine, Beckman Research Institute, City of Hope , Duarte, CA , USA

4. Division of Chemistry and Chemical Engineering, California Institute of Technology , Pasadena, CA, USA

5. Department of Surgery, University of Pittsburgh School of Medicine , Pittsburgh, PA, USA

6. Regulatory Biology Laboratory, Salk Institute for Biological Studies , La Jolla, CA , USA

Abstract

Abstract Pancreatic ductal progenitor cells have been proposed to contribute to adult tissue maintenance and regeneration after injury, but the identity of such ductal cells remains elusive. Here, from adult mice, we identify a near homogenous population of ductal progenitor-like clusters, with an average of 8 cells per cluster. They are a rare subpopulation, about 0.1% of the total pancreatic cells, and can be sorted using a fluorescence-activated cell sorter with the CD133highCD71lowFSCmid-high phenotype. They exhibit properties in self-renewal and tri-lineage differentiation (including endocrine-like cells) in a unique 3-dimensional colony assay system. An in vitro lineage tracing experiment, using a novel HprtDsRed/+ mouse model, demonstrates that a single cell from a cluster clonally gives rise to a colony. Droplet RNAseq analysis demonstrates that these ductal clusters express embryonic multipotent progenitor cell markers Sox9, Pdx1, and Nkx6-1, and genes involved in actin cytoskeleton regulation, inflammation responses, organ development, and cancer. Surprisingly, these ductal clusters resist prolonged trypsin digestion in vitro, preferentially survive in vivo after a severe acinar cell injury and become proliferative within 14 days post-injury. Thus, the ductal clusters are the fundamental units of progenitor-like cells in the adult murine pancreas with implications in diabetes treatment and tumorigenicity.

Funder

National Institutes of Health

National Pancreas Foundation

Ford Foundation

Publisher

Oxford University Press (OUP)

Reference65 articles.

1. Cell proliferation and migration as revealed by radioautography after injection of thymidine-H3 into male rats and mice;Messier,1960

2. Replication and regeneration of the pancreas;Elsasser,1993

3. Regulation of normal and adaptive pancreatic growth;Williams,2017

4. PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistance;Kulkarni,2004

5. Preexisting pancreatic acinar cells contribute to acinar cell, but not islet beta cell, regeneration;Desai,2007

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Isolation of Mouse Pancreatic Endothelial Cells;Journal of Visualized Experiments;2024-06-21

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3