Long-Term Culture of Self-renewing Pancreatic Progenitors Derived from Human Pluripotent Stem Cells

Autor: Simon M. Cool, Lawrence W. Stanton, Mohammad Shboul, Simon Denil, Drew M. Titmarsh, Giulia Rancati, Justin J. Cooper-White, Ee Kim Tan, Jamie Trott, Sheena Ong, Bruno Reversade, Maybelline Giam, Jiaxu Wang, Michelle Eio, N. Ray Dunn, Cheng Kit Wong
Přispěvatelé: Lee Kong Chian School of Medicine (LKCMedicine), School of Biological Sciences
Rok vydání: 2017
Předmět:
0301 basic medicine
Cellular differentiation
Mice
SCID
Culture Conditions
Kidney
self-renewal
Biochemistry
Pancreatic Progenitors
Mice
Mice
Inbred NOD
Insulin-Secreting Cells
Insulin
Cell Self Renewal
β cell differentiation
Induced pluripotent stem cell
lcsh:QH301-705.5
lcsh:R5-920
Stem Cells
Cell Differentiation
SOX9 Transcription Factor
Cell biology
Endothelial stem cell
medicine.anatomical_structure
tissue stem cells
PDX1
Stem cell
lcsh:Medicine (General)
Pancreas
Pluripotent Stem Cells
Transplantation
Heterologous
Down-Regulation
Biology
Article
Cell Line
03 medical and health sciences
pancreatic development
Directed differentiation
culture conditions
Genetics
medicine
Animals
Humans
Progenitor cell
pancreatic progenitors
Homeodomain Proteins
directed differentiation
Feeder Cells
Cell Biology
030104 developmental biology
lcsh:Biology (General)
Immunology
Trans-Activators
Developmental Biology
Zdroj: Stem Cell Reports, Vol 8, Iss 6, Pp 1675-1688 (2017)
Stem Cell Reports
ISSN: 2213-6711
Popis: Summary 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.
Highlights • Culture on 3T3 cells enables long-term self-renewal of human pancreatic progenitors • Proliferation requires EGF, FGF10, retinoic acid, and inhibition of Notch and TGF-β • Cultured progenitors upregulate genes required for mitosis and telomere maintenance • Pancreatic duct and β-like cells are generated in vitro and in vivo
In this article, Trott and colleagues describe conditions that enable long-term self-renewal of pancreatic progenitors derived from human pluripotent stem cells. These cultured pancreatic progenitors can be expanded for at least 20 passages and are capable of differentiation into multiple pancreatic lineages, including β-like cells, both in vitro and in vivo.
Databáze: OpenAIRE
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