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Series GSE126681 Query DataSets for GSE126681
Status Public on Aug 31, 2020
Title Pleiotrophic roles of VEGF during neonatal thymic development
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary In this report, we show that VEGF-blockade in neonates induces rapid changes in all three stromal compartments of the thymus, and that these changes recapitulate the maturation of these cell types seen during the transition from the neonatal to the young adult thymus. These changes in the microenvironment occur prior to the loss of thymocytes, and include not only a loss of cTECs relative to mTECs but also depletion of CD146+CD140aneg cells, a novel population of pericytes we have identified in the neonatal thymus. Importantly, we show that based on receptor expression and receptor blockade, VEGF drives the fetal/neonatal phenotype of the thymus through distinct VEGFR2- and NRP1-dependent pathways in thymic endothelial and mesenchymal cells respectively. In addition, receptor signaling induces changes in critical pathways affecting the function of all three compartments, with consequences on thymopoieisis.
Overall design To investigate the role of VEGF in the neonatal thymic microenvironment, we treated P1 mice with either Aflibercept (aka VEGF-Trap), a VEGFR1/R2 fusion protein which acts as a decoy molecule for all VEGF-A isoforms, or an hFC control antibody. Thymi were harvested 2 days post injection (P3), digested and depleted from thymocytes (CD45 magnetic depletion). Thymic stromal cells were isolated by fluorescence activated cell sorting as follows: within the stromal cell gate (CD3-CD4-CD8-CD45-Ter119- cells), thymic epithelial cells (TECs) were identified by their expression of the epithelial cell adhesion molecule (EpCAM) and were further subdivided into cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells (mTECs) based on high to low/negative Ly51 expression, respectively. Platelet endothelial cell adhesion molecule (PECAM-1 aka CD31) expression allowed the isolation of endothelial cells. By excluding endothelial, epithelial and hematopoietic cells, we next examined the mesenchymal population of the thymus. CD146+ and CD140a+ mesenchymal cells were isolated within the EpCAMnegCD31neg stromal cell gate.
Contributor(s) de Barros SC, Suterwala BT, He C, Ge S, Blumberg GK, Kim K, Klein S, Zhu Y, Chick B, Wang X, Casero D, Crooks GM
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Submission date Feb 18, 2019
Last update date Sep 01, 2020
Contact name Gay Miriam Crooks
Phone 3102060205
Organization name University of California Los Angeles
Department Pathology & Laboratory Med
Street address 610 Charles E. Young Drive, East
City Los Angeles
State/province California
ZIP/Postal code 90095
Country USA
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (30)
GSM3611169 CD140a+ mesenchymal cell, Control #1
GSM3611170 CD140a+ mesenchymal cell, Control #2
GSM3611171 CD140a+ mesenchymal cell, VEGF-Trap #1
BioProject PRJNA522986
SRA SRP186162

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Supplementary file Size Download File type/resource
GSE126681_GCSBmmThymicStroma.genes.fpkm.txt.gz 1.1 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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