E-GEOD-43133 - CD47 Inhibits Self-renewal and Reprogramming by Regulating c-Myc and Other Stem Cell Transcription Factors

Status
Released on 10 July 2013, last updated on 15 July 2013
Organism
Mus musculus
Samples (12)
Array (1)
Protocols (7)
Description
Signaling through the thrombospondin-1 receptor CD47 broadly limits cell and tissue survival of stress, but the molecular mechanisms are incompletely understood. We now show that loss of CD47 permits sustained proliferation of primary murine endothelial cells and enables these cells to spontaneously reprogram to form multipotent embryoid bodies. c-Myc, Klf4, Oct4, and Sox2 expression is elevated in CD47-null endothelial cells, in several tissues of CD47- or thrombospondin-1-null mice, and in a human T cell line lacking CD47. CD47 knockdown acutely increases mRNA levels of c-Myc and other stem cell transcription factors in cells and in vivo, whereas CD47 ligation by thrombospondin-1 suppresses c-Myc expression. The inhibitory effects of increasing CD47 levels can be overcome by maintaining c-Myc expression and are absent in cells with dysregulated c-Myc. Thus, CD47 antagonists enable cell self-renewal and reprogramming by overcoming negative regulation of c-Myc and other stem cell transcription factors. To identify gene expression changes associated with CD47 null cells, we compared the gene expression profile of these cells with WT endothelial cell, CD47 null Embryoid bodies cells and an established Embryonic Stem cell line.
Experiment type
transcription profiling by array 
Contacts
abdel elkahloun <abdel@mail.nih.gov>, Abdel G Elkahloun, David D Roberts, Sukhbir Kaur
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-43133.idf.txt
Sample and data relationshipE-GEOD-43133.sdrf.txt
Raw data (1)E-GEOD-43133.raw.1.zip
Processed data (1)E-GEOD-43133.processed.1.zip
Array designA-AFFY-130.adf.txt
Links