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Methylcellulose colony assay and single-cell micro-manipulation reveal progenitor-like cells in adult human pancreatic ducts
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. E...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10031308/ https://www.ncbi.nlm.nih.gov/pubmed/36868230 http://dx.doi.org/10.1016/j.stemcr.2023.02.001 |
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author | Quijano, Janine C. Wedeken, Lena Ortiz, Jose A. Zook, Heather N. LeBon, Jeanne M. Luo, Angela Rawson, Jeffrey Tremblay, Jacob R. Mares, Jacob M. Lopez, Kassandra Chen, Min-Hsuan Jou, Kevin Mendez-Dorantes, Carlos Al-Abdullah, Ismail H. Thurmond, Debbie C. Kandeel, Fouad Riggs, Arthur D. Ku, Hsun Teresa |
author_facet | Quijano, Janine C. Wedeken, Lena Ortiz, Jose A. Zook, Heather N. LeBon, Jeanne M. Luo, Angela Rawson, Jeffrey Tremblay, Jacob R. Mares, Jacob M. Lopez, Kassandra Chen, Min-Hsuan Jou, Kevin Mendez-Dorantes, Carlos Al-Abdullah, Ismail H. Thurmond, Debbie C. Kandeel, Fouad Riggs, Arthur D. Ku, Hsun Teresa |
author_sort | Quijano, Janine C. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10031308 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-100313082023-03-23 Methylcellulose colony assay and single-cell micro-manipulation reveal progenitor-like cells in adult human pancreatic ducts Quijano, Janine C. Wedeken, Lena Ortiz, Jose A. Zook, Heather N. LeBon, Jeanne M. Luo, Angela Rawson, Jeffrey Tremblay, Jacob R. Mares, Jacob M. Lopez, Kassandra Chen, Min-Hsuan Jou, Kevin Mendez-Dorantes, Carlos Al-Abdullah, Ismail H. Thurmond, Debbie C. Kandeel, Fouad Riggs, Arthur D. Ku, Hsun Teresa Stem Cell Reports Article 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. Elsevier 2023-03-02 /pmc/articles/PMC10031308/ /pubmed/36868230 http://dx.doi.org/10.1016/j.stemcr.2023.02.001 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Quijano, Janine C. Wedeken, Lena Ortiz, Jose A. Zook, Heather N. LeBon, Jeanne M. Luo, Angela Rawson, Jeffrey Tremblay, Jacob R. Mares, Jacob M. Lopez, Kassandra Chen, Min-Hsuan Jou, Kevin Mendez-Dorantes, Carlos Al-Abdullah, Ismail H. Thurmond, Debbie C. Kandeel, Fouad Riggs, Arthur D. Ku, Hsun Teresa Methylcellulose colony assay and single-cell micro-manipulation reveal progenitor-like cells in adult human pancreatic ducts |
title | Methylcellulose colony assay and single-cell micro-manipulation reveal progenitor-like cells in adult human pancreatic ducts |
title_full | Methylcellulose colony assay and single-cell micro-manipulation reveal progenitor-like cells in adult human pancreatic ducts |
title_fullStr | Methylcellulose colony assay and single-cell micro-manipulation reveal progenitor-like cells in adult human pancreatic ducts |
title_full_unstemmed | Methylcellulose colony assay and single-cell micro-manipulation reveal progenitor-like cells in adult human pancreatic ducts |
title_short | Methylcellulose colony assay and single-cell micro-manipulation reveal progenitor-like cells in adult human pancreatic ducts |
title_sort | methylcellulose colony assay and single-cell micro-manipulation reveal progenitor-like cells in adult human pancreatic ducts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10031308/ https://www.ncbi.nlm.nih.gov/pubmed/36868230 http://dx.doi.org/10.1016/j.stemcr.2023.02.001 |
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