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Methylcellulose colony assay and single-cell micro-manipulation reveal progenitor-like cells in adult human pancreatic ducts.

Authors
  • Quijano, Janine C1
  • Wedeken, Lena2
  • Ortiz, Jose A3
  • Zook, Heather N3
  • LeBon, Jeanne M2
  • Luo, Angela2
  • Rawson, Jeffrey2
  • Tremblay, Jacob R2
  • Mares, Jacob M2
  • Lopez, Kassandra2
  • Chen, Min-Hsuan4
  • Jou, Kevin2
  • Mendez-Dorantes, Carlos5
  • Al-Abdullah, Ismail H2
  • Thurmond, Debbie C6
  • Kandeel, Fouad7
  • Riggs, Arthur D8
  • Ku, Hsun Teresa3
  • 1 Department of Translational Research & Cellular Therapeutics, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA. Electronic address: [email protected].
  • 2 Department of Translational Research & Cellular Therapeutics, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA.
  • 3 Department of Translational Research & Cellular Therapeutics, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA; Irell and Manella Graduate School of Biological Sciences, City of Hope, Duarte, CA 91010, USA.
  • 4 Integrative Genomics Core, City of Hope, Duarte, CA 91010, USA.
  • 5 Irell and Manella Graduate School of Biological Sciences, City of Hope, Duarte, CA 91010, USA.
  • 6 Department of Molecular & Cellular Endocrinology, City of Hope, Duarte, CA 91010, USA.
  • 7 Department of Translational Research & Cellular Therapeutics, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA; Department of Clinical Diabetes, Endocrinology & Metabolism, City of Hope, Duarte, CA 91010, USA.
  • 8 Department of Diabetes & Drug Discovery, City of Hope, Duarte, CA 91010, USA.
Type
Published Article
Journal
Stem Cell Reports
Publisher
Elsevier
Publication Date
Mar 14, 2023
Volume
18
Issue
3
Pages
618–635
Identifiers
DOI: 10.1016/j.stemcr.2023.02.001
PMID: 36868230
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Progenitor cells capable of self-renewal and differentiation in the adult human pancreas are an under-explored resource for regenerative medicine. Using micro-manipulation and three-dimensional colony assays we identify cells within the adult human exocrine pancreas that resemble progenitor cells. Exocrine tissues were dissociated into single cells and plated into a colony assay containing methylcellulose and 5% Matrigel. A subpopulation of ductal cells formed colonies containing differentiated ductal, acinar, and endocrine lineage cells, and expanded up to 300-fold with a ROCK inhibitor. When transplanted into diabetic mice, colonies pre-treated with a NOTCH inhibitor gave rise to insulin-expressing cells. Both colonies and primary human ducts contained cells that simultaneously express progenitor transcription factors SOX9, NKX6.1, and PDX1. In addition, in silico analysis identified progenitor-like cells within ductal clusters in a single-cell RNA sequencing dataset. Therefore, progenitor-like cells capable of self-renewal and tri-lineage differentiation either pre-exist in the adult human exocrine pancreas, or readily adapt in culture. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

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