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Status |
Public on Apr 23, 2012 |
Title |
Gene expression signatures for fractions of E7.5 whole embryos based on Endoglin and Flk-1 markers |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Much remains unknown about the signals that induce early mesoderm to initiate hematopoietic differentiation. Here we show that endoglin (Eng), a receptor for the TGFβ superfamily, identifies all cells with hematopoietic fate in the early embryo. These arise in an Eng+Flk1+ mesodermal precursor population at E7.5, a cell fraction also endowed with endothelial potential. In Eng knockout embryos, hematopoietic colony activity and numbers of CD71+Ter119+ erythroid progenitors were severely reduced. This coincided with severely reduced expression of embryonic globin and key BMP target genes including the hematopoietic regulators Scl, Gata1, Gata2 and Msx-1. To interrogate molecular pathways active in the earliest hematopoietic progenitors, we applied transcriptional profiling to sorted cells from E7.5 embryos. Eng+Flk-1+ progenitors co-expressed TGFβ and BMP receptors and target genes. Furthermore, Eng+Flk-1+ cells presented high levels of phospho-SMAD1/5, indicating active TGFβ and/or BMP signaling. Remarkably, under hematopoietic serum-free culture conditions, hematopoietic outgrowth of endoglin-expressing cells was dependent on TGFβ superfamily ligands: BMP4, BMP2, or TGF-β1. These data demonstrate that the E+F+ fraction at E7.5 represents mesodermal cells competent to respond to TGFb1, BMP4, or BMP2, shaping their hematopoietic development, and that endoglin is a critical regulator in this process by modulating TGF/BMP signaling.
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Overall design |
E7.5 pooled embryos (25 litters; 300 embryos approximately) were dissected and 3,000 cells were sorted in triplicate for Eng-Flk1-, Eng-Flk1+, Eng+Flk1+, and Eng+Flk1- fractions. Microarray results were analyzed with GeneSpring GX software.
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Contributor(s) |
Borges L, Iacovino M |
Citation(s) |
22535663 |
Submission date |
Apr 23, 2012 |
Last update date |
May 10, 2018 |
Contact name |
Rita Perlingeiro |
E-mail(s) |
perli032@umn.edu
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Organization name |
University of Minnesota
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Department |
Medicine
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Lab |
Perlingeiro Lab
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Street address |
312 Church ST SE; NHH 4-124
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City |
Minneapolis |
State/province |
MN |
ZIP/Postal code |
55455 |
Country |
USA |
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Platforms (1) |
GPL4134 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Feature Number version) |
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Samples (12)
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Relations |
BioProject |
PRJNA160973 |
Supplementary file |
Size |
Download |
File type/resource |
GSE37515_K1099_A3550_intensity_norm.txt.gz |
4.2 Mb |
(ftp)(http) |
TXT |
GSE37515_RAW.tar |
116.9 Mb |
(http)(custom) |
TAR (of TXT) |
Processed data included within Sample table |
Processed data are available on Series record |
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