Journal ArticleDOI
The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors
Yoshiya Kawaguchi,Bonnie Cooper,Maureen Gannon,Michael Ray,Raymond J. MacDonald,Christopher V.E. Wright +5 more
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TLDR
Rec recombination-based lineage tracing in vivo is used to show that PTF1a is expressed at these early stages in the progenitors of pancreatic ducts, exocrine and endocrine cells, rather than being an exocrine-specific gene as previously described.Abstract:
Pancreas development begins with the formation of buds at specific sites in the embryonic foregut endoderm. We used recombination-based lineage tracing in vivo to show that Ptf1a (also known as PTF1-p48) is expressed at these early stages in the progenitors of pancreatic ducts, exocrine and endocrine cells, rather than being an exocrine-specific gene as previously described. Moreover, inactivation of Ptf1a switches the character of pancreatic progenitors such that their progeny proliferate in and adopt the normal fates of duodenal epithelium, including its stem-cell compartment. Consistent with the proposal that Ptf1a supports the specification of precursors of all three pancreatic cell types, transgene-based expression of Pdx1, a gene essential to pancreas formation, from Ptf1a cis-regulatory sequences restores pancreas tissue to Pdx1-null mice that otherwise lack mature exocrine and endocrine cells because of an early arrest in organogenesis. These experiments provide evidence that Ptf1a expression is specifically connected to the acquisition of pancreatic fate by undifferentiated foregut endoderm.read more
Citations
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Journal ArticleDOI
Conditional inactivation of Myc impairs development of the exocrine pancreas
TL;DR: It is shown that tissue-specific deletion of Myc causes a slightly accelerated differentiation of pancreatic epithelial cells into endocrine cells and perturbs the proliferation of pancreatIC progenitors and acinar precursor cells during early development, resulting in a severe reduction of the epithelial cell mass of pancreati buds and an extensive acinar hypoplasia.
Book ChapterDOI
Zebrafish Pancreas Development and Regeneration: Fishing for Diabetes Therapies
TL;DR: How previous and ongoing studies in zebrafish and beyond are influencing the understanding of molecular mechanisms underlying various forms of diabetes and efforts to develop cell-based approaches to cure this increasingly widespread disease are reviewed.
Journal ArticleDOI
Heparin-Binding Epidermal Growth Factor-like growth factor eliminates constraints on activated Kras to promote rapid onset of pancreatic neoplasia
Kevin C. Ray,M E Moss,Jeffrey L. Franklin,Connie J. Weaver,James N. Higginbotham,Yan Song,Frank Revetta,Stacy A. Blaine,L R Bridges,K E Guess,Robert J. Coffey,Howard C. Crawford,Mary Kay Washington,Anna L. Means +13 more
TL;DR: It is demonstrated that two oncogenic events, mutation of Kras and production of the growth factor heparin-binding epidermal growth factor-like growth factor (HB-EGF), are sufficient for rapid and complete neoplastic transformation of the exocrine pancreas.
Journal ArticleDOI
Reprogramming into pancreatic endocrine cells based on developmental cues.
TL;DR: The present short review summarizes the hitherto known functions and interplays of several key factors involved in the development of the different endocrine cell lineages during pancreas morphogenesis, as well as their potential to direct the generation of beta-cells.
Journal ArticleDOI
Stem cells and diabetes treatment.
TL;DR: This recent activity is reviewed and presented with particular focus on directed differentiation from pluripotent embryonic stem cells (versus other stem/progenitor cell sources) based on knowledge from pancreatic β‐cell development and the parallel approach to controlling endogenous β‐ cell neogenesis.
References
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Journal ArticleDOI
Insulin-promoter-factor 1 is required for pancreas development in mice
TL;DR: The findings show that IPF1 is needed for the formation of the pancreas and suggest that it acts to determine the fate of common pancreatic precursor cells and/ or to regulate their propagation.
Journal ArticleDOI
Differentiation of Embryonic Stem Cells to Insulin-Secreting Structures Similar to Pancreatic Islets
Nadya Lumelsky,Olivier Blondel,Olivier Blondel,Pascal Laeng,Iván Velasco,Rea Ravin,Ronald D.G. McKay +6 more
TL;DR: This work generated cells expressing insulin and other pancreatic endocrine hormones from mouse ES cells that self-assemble to form three-dimensional clusters similar in topology to normal pancreatic islets where pancreatic cell types are in close association with neurons.
Journal ArticleDOI
PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum
Martin F. Offield,T. L. Jetton,Patricia A. Labosky,Michael Ray,Roland Stein,Mark A. Magnuson,Brigid L.M. Hogan,Christopher V.E. Wright +7 more
TL;DR: The pdx-1/beta-galactosidase fusion allele is expressed in pancreatic and duodenal cells in the absence of functional PDX-1, with expression continuing into perinatal stages with similar boundaries and expression levels, and offers additional insight into the role of p dx-1 in the determination and differentiation of the posterior foregut.
Journal ArticleDOI
Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors.
TL;DR: The results provide direct evidence that NGN3+ cells are islet progenitors during embryogenesis and in adult mice, and suggest that lineages for exocrine, endocrine islet and duct progenitor are committed at mid-gestation.