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Long-Term Culture of Self-renewing Pancreatic Progenitors Derived from Human Pluripotent Stem Cells.
- Source :
-
Stem cell reports [Stem Cell Reports] 2017 Jun 06; Vol. 8 (6), pp. 1675-1688. - Publication Year :
- 2017
-
Abstract
- Pluripotent stem cells have been proposed as an unlimited source of pancreatic β cells for studying and treating diabetes. However, the long, multi-step differentiation protocols used to generate functional β cells inevitably exhibit considerable variability, particularly when applied to pluripotent cells from diverse genetic backgrounds. We have developed culture conditions that support long-term self-renewal of human multipotent pancreatic progenitors, which are developmentally more proximal to the specialized cells of the adult pancreas. These cultured pancreatic progenitor (cPP) cells express key pancreatic transcription factors, including PDX1 and SOX9, and exhibit transcriptomes closely related to their in vivo counterparts. Upon exposure to differentiation cues, cPP cells give rise to pancreatic endocrine, acinar, and ductal lineages, indicating multilineage potency. Furthermore, cPP cells generate insulin+ β-like cells in vitro and in vivo, suggesting that they offer a convenient alternative to pluripotent cells as a source of adult cell types for modeling pancreatic development and diabetes.<br /> (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cell Differentiation drug effects
Cell Line
Down-Regulation
Feeder Cells cytology
Feeder Cells metabolism
Homeodomain Proteins genetics
Homeodomain Proteins metabolism
Humans
Insulin pharmacology
Insulin-Secreting Cells cytology
Insulin-Secreting Cells metabolism
Kidney metabolism
Kidney pathology
Mice
Mice, Inbred NOD
Mice, SCID
Pancreas cytology
Pluripotent Stem Cells metabolism
SOX9 Transcription Factor metabolism
Stem Cells metabolism
Trans-Activators metabolism
Transplantation, Heterologous
Cell Self Renewal physiology
Pluripotent Stem Cells cytology
Stem Cells cytology
Subjects
Details
- Language :
- English
- ISSN :
- 2213-6711
- Volume :
- 8
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Stem cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 28591650
- Full Text :
- https://doi.org/10.1016/j.stemcr.2017.05.019