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Series GSE40823 Query DataSets for GSE40823
Status Public on Sep 11, 2013
Title RNA-Seq profiling unveils a non-canonical Wnt signalling signature in pancreas versus liver fate decision
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Understanding how distinct cell types arise from common multipotent progenitor cells is a major quest in stem cell biology. This knowledge will aid in the targeted differentiation and growth of stem cells, but also in the discovery of the basis of cellular plasticity and of how tissue programming can be controlled. The liver and pancreas share many aspects of their early development, being both specified in the same region of the endoderm, and, possibly, originating from a common progenitor. However, how pancreas versus liver cell fate decision occurs during embryogenesis and the molecular basis of this cellular plasticity are poorly understood. Here, we use RNA-Seq to define the molecular identity of liver and pancreas progenitors directly in mouse embryos and to investigate the mechanisms regulating the emergence of liver or pancreas as alternative fates from the endoderm. Progenitor cell-specific RNA was obtained from mouse Prox1-EGFP-labeled embryonic cells isolated by FACS at distinct developmental stages, before and after the onset of organogenesis. By integrating the temporal and spatial gene expression profiles, we found mutually exclusive signaling signatures in hepatic and pancreatic progenitors. Importantly, we identified the non-canonical Wnt pathway as a potential developmental regulator of the pancreas versus liver fate decision, being expressed in the foregut endoderm, before the cell fate choice is made, and then maintained in pancreas progenitors but absent in hepatic progenitors. Moreover, when assayed in Xenopus embryos, the non-canonical Wnt pathway is able to promote pancreatic fate and repress hepatic fate in the endoderm, suggesting an ancient mechanism for controlling pancreas versus liver fate choice. We expect that this knowledge will be key to formulate reprogramming strategies to convert adult hepatic cells into pancreatic cells as a cell-based therapeutic approach for diabetes.
 
Overall design We performed sequencing-based expression profiling (RNA-Seq) of hepatic and pancreatic progenitors in the mouse at two distinct developmental stages.
 
Contributor(s) Mah N, Spagnoli FM
Citation(s) 24013505
Submission date Sep 12, 2012
Last update date May 15, 2019
Contact name Francesca M. Spagnoli
E-mail(s) francesca.spagnoli@kcl.ac.uk
Organization name King's College London
Department CGTRM
Lab Molecular and Cellular Basis of Embryonic Development
Street address Great Maze Pond
City London
ZIP/Postal code SE1 9RT
Country United Kingdom
 
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (5)
GSM1002562 foregut, E8.5
GSM1002563 medial foregut, E8.5
GSM1002564 liver, E10.5
Relations
BioProject PRJNA175044
SRA SRP015727

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE40823_SpagnoliFM_RNASeq.FPKM.txt.gz 534.2 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Processed data are available on Series record
Raw data are available in SRA

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