title: Cells with surface expression of CD133highCD71low are enriched for tripotent colony-forming progenitor cells in the adult murine pancreas.
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 (2-4month-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.
authors.affiliation: Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Duarte, CA 91010, United States; Beckman Research Institute of City of Hope, Duarte, CA 91010, United States; State Key Laboratory of Natural Medicines, Biopharmaceutical College, China Pharmaceutical University, Tongjia Xiang 24, Nanjing, 210009, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Duarte, CA 91010, United States; Beckman Research Institute of City of Hope, Duarte, CA 91010, United States.
authors.forename: Dan
authors.initials: D
authors.lastname: Gao
authors.affiliation: Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Duarte, CA 91010, United States; Beckman Research Institute of City of Hope, Duarte, CA 91010, United States.
authors.forename: Tao
authors.initials: T
authors.lastname: Feng
authors.affiliation: Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Duarte, CA 91010, United States; Irell & Manella Graduate School of Biological Sciences, Duarte, CA 91010, United States; Beckman Research Institute of City of Hope, Duarte, CA 91010, United States.
authors.forename: Jacob R
authors.initials: JR
authors.lastname: Tremblay
authors.affiliation: Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Duarte, CA 91010, United States; Irell & Manella Graduate School of Biological Sciences, Duarte, CA 91010, United States; Beckman Research Institute of City of Hope, Duarte, CA 91010, United States.
authors.forename: Nadiah
authors.initials: N
authors.lastname: Ghazalli
authors.affiliation: Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Duarte, CA 91010, United States; Beckman Research Institute of City of Hope, Duarte, CA 91010, United States.
authors.forename: Angela
authors.initials: A
authors.lastname: Luo
authors.affiliation: Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Duarte, CA 91010, United States; Beckman Research Institute of City of Hope, Duarte, CA 91010, United States.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Rawson
authors.affiliation: Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Duarte, CA 91010, United States; Beckman Research Institute of City of Hope, Duarte, CA 91010, United States.
authors.forename: Janine C
authors.initials: JC
authors.lastname: Quijano
authors.affiliation: Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Duarte, CA 91010, United States; Beckman Research Institute of City of Hope, Duarte, CA 91010, United States.
authors.forename: Jing
authors.initials: J
authors.lastname: Chai
authors.affiliation: Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Duarte, CA 91010, United States; Beckman Research Institute of City of Hope, Duarte, CA 91010, United States.
authors.forename: Lena
authors.initials: L
authors.lastname: Wedeken
authors.affiliation: Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Duarte, CA 91010, United States; Beckman Research Institute of City of Hope, Duarte, CA 91010, United States.
authors.forename: Jasper
authors.initials: J
authors.lastname: Hsu
authors.affiliation: Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Duarte, CA 91010, United States; Beckman Research Institute of City of Hope, Duarte, CA 91010, United States.
authors.forename: Jeanne
authors.initials: J
authors.lastname: LeBon
authors.affiliation: Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Duarte, CA 91010, United States; Beckman Research Institute of City of Hope, Duarte, CA 91010, United States.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Walker
authors.affiliation: Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Duarte, CA 91010, United States; Irell & Manella Graduate School of Biological Sciences, Duarte, CA 91010, United States; Beckman Research Institute of City of Hope, Duarte, CA 91010, United States.
authors.forename: Hung-Ping
authors.initials: HP
authors.lastname: Shih
authors.affiliation: Department of Bioengineering, California Institute of Technology, Pasadena, CA 91125, United States.
authors.forename: Alborz
authors.initials: A
authors.lastname: Mahdavi
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Tirrell
authors.affiliation: Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Duarte, CA 91010, United States; Irell & Manella Graduate School of Biological Sciences, Duarte, CA 91010, United States; Beckman Research Institute of City of Hope, Duarte, CA 91010, United States.
authors.forename: Arthur D
authors.initials: AD
authors.lastname: Riggs
authors.affiliation: Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Duarte, CA 91010, United States; Irell & Manella Graduate School of Biological Sciences, Duarte, CA 91010, United States; Beckman Research Institute of City of Hope, Duarte, CA 91010, United States. Electronic address: hku@coh.org.
authors.forename: H Teresa
authors.initials: HT
authors.lastname: Ku
mesh_terms: D000071916:AC133 Antigen; D061354:Acinar Cells / Q000166:cytology; D000375:Aging / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D000066673:Cell Self Renewal; D003114:Colony-Forming Units Assay; D005934:Glucagon / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D008810:Mice, Inbred C57BL; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D010179:Pancreas / Q000166:cytology*; D010183:Pancreatic Ducts / Q000166:cytology; D016612:Paraffin Embedding; D011990:Receptors, Transferrin / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D016707:Tissue Fixation
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; C068126:CD71 antigen; D007328:Insulin; D011990:Receptors, Transferrin; D005934:Glucagon
keywords: Differentiation; Fluorescence-activated cell sorting (FACS); Heterogeneity of ductal cells; Pancreatic colony-forming units; Self-renewal