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
[Master Transcription Regulators Specifying Cell-Lineage Fates in Development As Possible Therapeutic Targets in Oncology].
TL;DR: This review is an attempt to give a modern concept of master genes and their functions in adult stem cells of the organism and in carcinogenesis, with pancreatic cancer as an example.
Journal ArticleDOI
Generation and characterization of human insulin-releasing cell lines
Leticia Labriola,María Giselle Peters,Karin Krogh,Ivan Daniel Stigliano,Letícia Ferreira Terra,Cecilia Buchanan,Marcel Cerqueira César Machado,Elisa Bal de Kier Joffé,Lydia Puricelli,Mari Cleide Sogayar +9 more
TL;DR: Three human insulin-releasing cell lines are established which maintain antigenic characteristics and insulin secretion profiles of the original tumors, and represent valuable tools for the study of molecular events underlying beta cell function and dysfunction.
Book ChapterDOI
Circulating microRNAs in Diabetes Progression: Discovery, Validation, and Research Translation
TL;DR: To identify these transcripts, this work outlines miRNAs that play a central role in pancreas development and diabetes, as well as previously identifiedmiRNAs with differential expression in individuals with T1D and T2D.
Journal ArticleDOI
Non-cell autonomous control of precerebellar neuron migration by Slit and Robo proteins.
TL;DR: It is shown that Robo1 and Robo2 receptors act non-cell autonomously in migrating precerebellar neurons and that floor-plate signals, other than Slit proteins, must exist to prevent midline crossing.
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.