scholarly journals Jag1 modulates an oscillatory Dll1-Notch-Hes1 signaling module to coordinate growth and fate of pancreatic progenitors

2018 ◽  
Author(s):  
Philip A. Seymour ◽  
Caitlin A. Collin ◽  
Anuska l. R. Egeskov-Madsen ◽  
Mette C. Jørgensen ◽  
Hiromi Shimojo ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Progenitor Cells ◽  
Ductal Morphogenesis ◽  
Pancreatic Progenitor ◽  
Notch Activity ◽  
Pancreatic Progenitors ◽  
Pancreatic Progenitor Cells ◽  
Acinar To Ductal Metaplasia ◽  
Induced Changes ◽  
Experimentally Induced

SummaryNotch signaling controls proliferation of multipotent pancreatic progenitor cells (MPCs) and their segregation into bipotent progenitors (BPs) and unipotent pro-acinar cells (PACs). Here we uncover fast ultradian oscillations in the ligand Dll1, and the transcriptional effector Hes1, which proved crucial for MPC expansion. Conversely Jag1, a uniformly expressed ligand, curbed MPC growth, but as expression later segregated to PACs it proved critical for specifying all but the most proximal 5% of BPs, while BPs were entirely lost in Jag1, Dll1 double mutants. Moreover, experimentally induced changes in Hes1 oscillation parameters was associated with selective adoption of BP or PAC fates. Anatomically, ductal morphogenesis and organ architecture is minimally perturbed in Jag1 mutants until later stages, when ductal remodeling fails and signs of acinar-to-ductal metaplasia appear. Our study uncovers oscillating Notch activity in the developing pancreas, which along with modulation by Jag1 is required to coordinate MPC growth and fate.

scholarly journals Preservation of proliferating pancreatic progenitor cells by Delta-Notch signaling in the embryonic chicken pancreas

2007 ◽  
Vol 7 (1) ◽  
pp. 63 ◽  
Author(s):  
Jonas Ahnfelt-Rønne ◽  
Jacob Hald ◽  
Anne Bødker ◽  
Hani Yassin ◽  
Palle Serup ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Progenitor Cells ◽  
Pancreatic Progenitor ◽  
Embryonic Chicken ◽  
Pancreatic Progenitor Cells ◽  
Chicken Pancreas

scholarly journals MFng Is Dispensable for Mouse Pancreas Development and Function

2009 ◽  
Vol 29 (8) ◽  
pp. 2129-2138 ◽  
Author(s):  
Per Svensson ◽  
Ingela Bergqvist ◽  
Stefan Norlin ◽  
Helena Edlund
Keyword(s):  
Cell Differentiation ◽  
Notch Signaling ◽  
Pancreas Development ◽  
Loss Of Function ◽  
Pancreatic Cell ◽  
Targeted Deletion ◽  
Mouse Pancreas ◽  
Pancreatic Progenitor ◽  
Pancreatic Progenitor Cells ◽  
And Function

ABSTRACT Notch signaling regulates pancreatic cell differentiation, and mutations of various Notch signaling components result in perturbed pancreas development. Members of the Fringe family of β1,3-N-acetylglucosaminyltransferases, Manic Fringe (MFng), Lunatic Fringe (LFng), and Radical Fringe (RFng), modulate Notch signaling, and MFng has been suggested to regulate pancreatic endocrine cell differentiation. We have characterized the expression of the three mouse Fringe genes in the developing mouse pancreas between embryonic days 9 and 14 and show that the expression of MFng colocalized with the proendocrine transcription factor Ngn3. In contrast, the expression of LFng colocalized with the exocrine marker Ptf1a, whereas RFng was not expressed. Moreover, we show that expression of MFng is lost in Ngn3 mutant mice, providing evidence that MFng is genetically downstream of Ngn3. Gain- and loss-of-function analyses of MFng by the generation of mice that overexpress MFng in early pancreatic progenitor cells and mice with a targeted deletion of MFng provide, however, evidence that MFng is dispensable for pancreas development and function, since no pancreatic defects in these mice were observed.

scholarly journals Human Fetal Bone Marrow-Derived Mesenchymal Stem Cells Promote the Proliferation and Differentiation of Pancreatic Progenitor Cells and the Engraftment Function of Islet-Like Cell Clusters

2019 ◽  
Vol 20 (17) ◽  
pp. 4083
Author(s):  
Xing Yu Li ◽  
Shang Ying Wu ◽  
Po Sing Leung
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Progenitor Cells ◽  
Pancreatic Progenitor ◽  
Pancreatic Progenitor Cells ◽  
Proliferation And Differentiation ◽  
Differentiation And Proliferation

Pancreatic progenitor cells (PPCs) are the primary source for all pancreatic cells, including beta-cells, and thus the proliferation and differentiation of PPCs into islet-like cell clusters (ICCs) opens an avenue to providing transplantable islets for diabetic patients. Meanwhile, mesenchymal stem cells (MSCs) can enhance the development and function of different cell types of interest, but their role on PPCs remains unknown. We aimed to explore the mechanism-of-action whereby MSCs induce the in vitro and in vivo PPC/ICC development by means of our established co-culture system of human PPCs with human fetal bone marrow-derived MSCs. We examined the effect of MSC-conditioned medium on PPC proliferation and survival. Meanwhile, we studied the effect of MSC co-culture enhanced PPC/ICC function in vitro and in vivo co-/transplantation. Furthermore, we identified IGF1 as a critical factor responsible for the MSC effects on PPC differentiation and proliferation via IGF1-PI3K/Akt and IGF1-MEK/ERK1/2, respectively. In conclusion, our data indicate that MSCs stimulated the differentiation and proliferation of human PPCs via IGF1 signaling, and more importantly, promoted the in vivo engraftment function of ICCs. Taken together, our protocol may provide a mechanism-driven basis for the proliferation and differentiation of PPCs into clinically transplantable islets.

scholarly journals Genetic Modification of Primate Amniotic Fluid-Derived Stem Cells Produces Pancreatic Progenitor Cells in vitro

2013 ◽  
Vol 197 (4) ◽  
pp. 269-282 ◽  
Author(s):  
Yu Zhou ◽  
David L. Mack ◽  
J. Koudy Williams ◽  
Sayed-Hadi Mirmalek-Sani ◽  
Emily Moorefield ◽  
...  
Keyword(s):  
Stem Cells ◽  
Amniotic Fluid ◽  
Progenitor Cells ◽  
Genetic Modification ◽  
Pancreatic Progenitor ◽  
Pancreatic Progenitor Cells
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