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Series GSE35894 Query DataSets for GSE35894
Status Public on Feb 08, 2013
Title Hypoxia-induced Arterial Differentiation Requires Adrenomedullin and Notch Signaling
Organism Mus musculus
Experiment type Expression profiling by array
Summary Hypoxia (low oxygen) and Notch signaling are two important regulators of vascular development, but how they interact in controlling the choice between arterial and venous fates for endothelial cells during vasculogenesis is less well understood. In this report, we show that hypoxia and Notch signaling intersect in promotion of arterial differentiation. Hypoxia upregulated expression of the Notch ligand Dll4 and increases Notch signaling, in a process requiring the vasoactive hormone adrenomedullin but not endogenous VEGF. Notch signaling also upregulated Dll4 expression, leading to a positive feedback loop sustaining Dll4 expression and Notch signaling. In addition, functional Notch signaling was required for hypoxia to upregulate the arterial marker genes Depp, connexin40 (Gja5), Cxcr4 and Hey1. In conclusion, the data reveal an intricate interaction between hypoxia and Notch signaling in the control of endothelial cell differentiation, including a hypoxia/adrenomedullin/Dll4 axis that initiates Notch signaling and a requirement for Notch signaling to effectuate hypoxiamediated induction of the arterial differentiation program.
 
Overall design 12 microarray samples consisting of >50,000 FACS sorted CD31+ cells purified from wild type mouse CCE ES cells that were differentiated into the endothelial lineages in 3 biological replicates. The ES cells were subjected to embryoid body formation over 4 days in hanging drop cultures, FACS sorted for Flk1 positive vascular progenitors cells and plated for a further 4 days in normoxia (21% oxygen) or hypoxia (1.5-2% oxygen) with or without 4 umol/l gamma-secretase inhibitor L-685.458.
 
Contributor(s) Lanner F, Lee KL, Ortega GC, Sohl M, Li X, Jin S, Hansson EM, Claesson-Welsh L, Poellinger L, Lendahl U, Farnebo F
Citation(s) 23379656
Submission date Feb 16, 2012
Last update date Jun 14, 2018
Contact name Kian Leong LEE
E-mail(s) kianleong.lee@duke-nus.edu.sg
Phone +(65) 6601 3685
Organization name National University of Singapore (NUS)
Department Duke-NUS Medical School
Lab Cancer & Stem Cell Biology Program (CSCB)
Street address #07-21, 8 College Road
City Singapore
State/province Singapore
ZIP/Postal code 169857
Country Singapore
 
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (12)
GSM877114 CD31 Positive Cells + Normoxia (21% O2) Replicate 1
GSM877115 CD31 Positive Cells + Normoxia (21% O2) Replicate 2
GSM877116 CD31 Positive Cells + Normoxia (21% O2) Replicate 3
Relations
BioProject PRJNA151953

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE35894_RAW.tar 3.1 Mb (http)(custom) TAR
GSE35894_non-normalized.txt.gz 2.0 Mb (ftp)(http) TXT
Processed data included within Sample table
Raw data are available on Series record

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