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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METTL13 Methylation of eEF1A Increases Translational Output to Promote Tumorigenesis
Shuo Liu,Simone Hausmann,Scott M. Carlson,Mary Esmeralda Fuentes,Joel William Francis,Renjitha Pillai,Shane Lofgren,Laura Hulea,Kristofferson Tandoc,Jiuwei Lu,Ami Li,Nicholas D. Nguyen,Marcello Caporicci,Michael Paul Kim,Anirban Maitra,Huamin Wang,Ignacio I. Wistuba,John A. Porco,Michael C. Bassik,Joshua E. Elias,Jikui Song,Ivan Topisirovic,Capucine Van Rechem,Pawel K. Mazur,Or Gozani +24 more
TL;DR: It is demonstrated that METTL13 (methyltransferase-like 13) dimethylation of eEF1A (eukaryotic elongation factor 1A) lysine 55 (eEF1AK55me2) is utilized by Ras-driven cancers to increase translational output and promote tumorigenesis in vivo, and suggests thatMETTL13 inhibition may constitute a targetable vulnerability of tumors driven by aberrant Ras signaling.
Journal ArticleDOI
Control of β-Cell Differentiation by the Pancreatic Mesenchyme
Myriam Attali,Volodymyr Stetsyuk,A. Basmaciogullari,Virginie Aiello,Maria A. Zanta-Boussif,Bertrand Duvillié,Raphael Scharfmann +6 more
TL;DR: The results indicate that expansion of early PDX1+ pancreatic progenitor cells represents a way to increase the final number of β-cells developing from early embryonic pancreas.
Journal ArticleDOI
A vHNF1/TCF2-HNF6 cascade regulates the transcription factor network that controls generation of pancreatic precursor cells.
Aurélie V. Poll,Christophe E. Pierreux,Ludmilla Lokmane,Cécile Haumaitre,Younes Achouri,Patrick Jacquemin,Guy G. Rousseau,Silvia Cereghini,Frédéric P. Lemaigre +8 more
TL;DR: The sequential activation of vHNF1, HNF6, and Pdx1 in the endoderm appears to control the generation of pancreatic precursors, and this cascade may be used to benchmark in vitro differentiation of Pancic precursor cells from embryonic stem cells, for cell therapy of diabetes.
Journal ArticleDOI
Transcriptional regulation by NR5A2 links differentiation and inflammation in the pancreas
Isidoro Cobo,Paola Martinelli,Marta Flández,Latifa Bakiri,Mingfeng Zhang,Enrique Carrillo-de-Santa-Pau,Jinping Jia,Victor J. Sanchez-Arévalo Lobo,Diego Megías,Irene Felipe,Natalia del Pozo,Irene Millán,Liv Thommesen,Torunn Bruland,Sara H. Olson,Jill P. Smith,Kristina Schoonjans,William R. Bamlet,Gloria M. Petersen,Núria Malats,Laufey T. Amundadottir,Erwin F. Wagner,Francisco X. Real +22 more
TL;DR: An epithelial-cell-autonomous basal pre-inflammatory state in the pancreas of Nr5a2+/− mice is described that is reminiscent of the early stages of pancreatitis-induced inflammation and is conserved in histologically normal human pancreases with reduced expression of NR5A2 mRNA.
Journal ArticleDOI
Specification of Spatial Identities of Cerebellar Neuron Progenitors by Ptf1a and Atoh1 for Proper Production of GABAergic and Glutamatergic Neurons
Mayumi Yamada,Yusuke Seto,Shinichiro Taya,Tomoo Owa,Yukiko U. Inoue,Takayoshi Inoue,Yoshiya Kawaguchi,Yo-ichi Nabeshima,Mikio Hoshino +8 more
TL;DR: It is suggested that Ptf1a and Atoh1 specify spatial identities of cerebellar neuron progenitors in the neuroepithelium, leading to appropriate production of GABAergic and glutamatergic neurons, respectively.
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.