TY - JOUR
T1 - Long-Term Culture of Self-renewing Pancreatic Progenitors Derived from Human Pluripotent Stem Cells
AU - Trott, Jamie
AU - Tan, Ee Kim
AU - Ong, Sheena
AU - Titmarsh, Drew M.
AU - Denil, Simon L.I.J.
AU - Giam, Maybelline
AU - Wong, Cheng Kit
AU - Wang, Jiaxu
AU - Shboul, Mohammad
AU - Eio, Michelle
AU - Cooper-White, Justin
AU - Cool, Simon M.
AU - Rancati, Giulia
AU - Stanton, Lawrence W.
AU - Reversade, Bruno
AU - Dunn, N. Ray
N1 - Generated from Scopus record by KAUST IRTS on 2023-02-15
PY - 2017/6/6
Y1 - 2017/6/6
N2 - 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.
AB - 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.
UR - https://linkinghub.elsevier.com/retrieve/pii/S2213671117302266
UR - http://www.scopus.com/inward/record.url?scp=85020316164&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2017.05.019
DO - 10.1016/j.stemcr.2017.05.019
M3 - Article
SN - 2213-6711
VL - 8
SP - 1675
EP - 1688
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 6
ER -
