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Cells with surface expression of CD133^(high)CD71^(low) are enriched for tripotent colony-forming progenitor cells in the adult murine pancreas

Jin, Liang and Gao, Dan and Feng, Tao and Tremblay, Jacob R. and Ghazalli, Nadiah and Luo, Angela and Rawson, Jeffrey and Quijano, Janine C. and Chai, Jing and Wedeken, Lena and Hsu, Jasper and LeBon, Jeanne and Walker, Stephanie and Shih, Hung-Ping and Mahdavi, Alborz and Tirrell, David A. and Riggs, Arthur D. and Ku, H. Teresa (2016) Cells with surface expression of CD133^(high)CD71^(low) are enriched for tripotent colony-forming progenitor cells in the adult murine pancreas. Stem Cell Research, 16 (1). pp. 40-53. ISSN 1873-5061. PMCID PMC4762724. https://resolver.caltech.edu/CaltechAUTHORS:20160104-143534788

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Abstract

Progenitor cells in the adult pancreas are potential sources of endocrine beta cells for treating type 1 diabetes. Previously, we identified tri-potent progenitor cells in the adult (2–4 month-old) murine pancreas that were capable of self-renewal and differentiation into duct, acinar, and endocrine cells in vitro. These progenitor cells were named pancreatic colony-forming units (PCFUs). However, because PCFUs are a minor population in the pancreas (~ 1%) they are difficult to study. To enrich PCFUs, strategies using cell-surface marker analyses and fluorescence-activated cell sorting were developed. We found that CD133^(high)CD71^(low) cells, but not other cell populations, enriched PCFUs by up to 30 fold compared to the unsorted cells. CD133^(high)CD71^(low) cells generated primary, secondary, and subsequent colonies when serially re-plated in Matrigel-containing cultures, suggesting self-renewal abilities. In the presence of a laminin hydrogel, CD133^(high)CD71^(low) cells gave rise to colonies that contained duct, acinar, and Insulin+ Glucagon+ double-hormonal endocrine cells. Colonies from the laminin hydrogel culture were implanted into diabetic mice, and five weeks later duct, acinar, and Insulin+ Glucagon− cells were detected in the grafts, demonstrating tri-lineage differentiation potential of CD133^(high)CD71^(low) cells. These CD133^(high)CD71^(low) cells will enable future studies of putative adult pancreas stem cells in vivo.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.scr.2015.11.015DOIArticle
http://www.sciencedirect.com/science/article/pii/S1873506115001683PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762724/PubMed CentralArticle
ORCID:
AuthorORCID
Mahdavi, Alborz0000-0002-8790-8112
Tirrell, David A.0000-0003-3175-4596
Additional Information:© 2015 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Received 11 July 2014. Received in revised form 7 November 2015. Accepted 25 November 2015. Available online 30 November 2015. This work is supported in part by the National Institutes of Health (NIH) grants R01DK081587 and R01DK099734 to H.T.K. and U01DK089533 to A.D.R., National Science Foundation grant NSF-DMR-1206121 and California Institute for Regenerative Medicine grant RB5-07398 to D.A.T., and Office of Naval Research ONR-N00014-02-1 0958 and NSF-DBI-9970143 to the Electron Microscopy Core facility at City of Hope. Support from the Joseph J. Jacobs Institute for Molecular Engineering for Medicine at Caltech is also gratefully acknowledged. L.J. is supported by the National High Technology Research and Development Program of China (863 Program, No. 2015AA020314), Excellent Youth Foundation of Jiangsu Scientific Committee (BK20140029), the Fundamental Research Funds for the Central Universities (Z114037), Priority Academic Program Development of Jiangsu Higher Education Institutions, and the National Natural Science Foundation of China (No. 81570696). Research reported in this publication included work performed in the Analytical Cytometry Core and Light Microscopy Digital Imaging Core supported by the National Cancer Institute of the National Institutes of Health under award number P30CA33572. The sponsor did not participate in the study design, collection, analysis, or interpretation of data. Author Responsibilities: Liang Jin, Dan Gao: study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript. Tao Feng, Angela Luo, Jeffery Rawson, Janine Quijano, Jing Chai, Lena Wedeken, Nadiah Ghazalli, Jasper Hsu, Jeanne LeBon, Stephanie Walker, Jacob Tremblay: acquisition of data, analysis and interpretation of data. Alborz Mahdavi, Hung-Ping Shih: technical or material support. David A. Tirrell, Arthur D. Riggs: technical or material support, critical revision of the manuscript for important intellectual content, obtained funding. Hsun Teresa Ku: study concept and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, obtained funding. The authors have nothing to disclose.
Funders:
Funding AgencyGrant Number
NIHR01DK081587
NIHR01DK099734
NIHU01DK089533
NSFDMR-1206121
California Institute for Regenerative Medicine (CIRM)RB5-07398
Office of Naval Research (ONR)N00014-02-1 0958
NSFDBI-9970143
Joseph J. Jacobs Institute for Molecular Engineering for MedicineUNSPECIFIED
National High Technology Research and Development Program of China2015AA020314
Excellent Youth Foundation of Jiangsu Scientific CommitteeBK20140029
Fundamental Research Funds for the Central UniversitiesZ114037
Priority Academic Program Development of Jiangsu Higher Education InstitutionsUNSPECIFIED
National Natural Science Foundation of China81570696
National Cancer InstituteP30CA33572
Subject Keywords:Pancreatic colony-forming units; Fluorescence-activated cell sorting (FACS); Differentiation; Self-renewal; Heterogeneity of ductal cells
Issue or Number:1
PubMed Central ID:PMC4762724
Record Number:CaltechAUTHORS:20160104-143534788
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160104-143534788
Official Citation:Liang Jin, Dan Gao, Tao Feng, Jacob R. Tremblay, Nadiah Ghazalli, Angela Luo, Jeffrey Rawson, Janine C. Quijano, Jing Chai, Lena Wedeken, Jasper Hsu, Jeanne LeBon, Stephanie Walker, Hung-Ping Shih, Alborz Mahdavi, David A. Tirrell, Arthur D. Riggs, H. Teresa Ku, Cells with surface expression of CD133highCD71low are enriched for tripotent colony-forming progenitor cells in the adult murine pancreas, Stem Cell Research, Volume 16, Issue 1, January 2016, Pages 40-53, ISSN 1873-5061, http://dx.doi.org/10.1016/j.scr.2015.11.015. (http://www.sciencedirect.com/science/article/pii/S1873506115001683)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:63344
Collection:CaltechAUTHORS
Deposited By: Irina Meininger
Deposited On:04 Jan 2016 22:59
Last Modified:03 Oct 2019 09:27

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