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Series GSE115137 Query DataSets for GSE115137
Status Public on Dec 19, 2018
Title The transcriptome of human endometrial mesenchymal stem cells under TGFβR inhibition reveals improved potential for cell-based therapies
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Mesenchymal stem/stromal cells (MSCs) are multipotent cells with favorable properties for cell therapy and regenerative medicine. Human endometrium harbors a small population of perivascular, clonogenic MSCs (eMSCs) identified by the SUSD2 marker. As for other MSCs, eMSCs require extensive in vitro expansion to generate clinically relevant numbers of cells, resulting in spontaneous differentiation, replicative senescence, and cell death, decreasing therapeutic potency. We previously demonstrated that A83-01, a TGF-b receptor inhibitor maintained eMSCs clonogenicity, promoted proliferation, prevented apoptosis and maintained MSC function in vitro. Here we compare the transcriptome of passaged eMSCs from six women cultured with and without A83-01 for 7 days. We identified 1206 differentially expressed genes using a false discovery rate cut-off at 0.01 and fold change >2. Significant enrichment of genes involved in inflammatory responses, angiogenesis, cell migration and proliferation, and reduced smooth muscle proliferation, collagen fibril and extracellular matrix organization genes were revealed. TGF-b, Wnt and Akt signaling pathways were decreased. Anti-fibrotic and anti-apoptotic genes were induced, and fibroblast proliferation and myofibroblast related genes were down-regulated. We validated the enhanced potency of A83-01-treated eMSCs and found increased MSC potency genes (TWIST1, TWIST2, JAG1, LIFR, and SLIT2) and no pluripotency gene expression. Increased angiogenic capacity was functionally demonstrated in vitro, and our angiogenic and cytokine protein arrays further confirmed the angiogenic, antifibrotic and immunomodulatory phenotype of A83-01-treated eMSCs. Overall, we showed that eMSCs culture expanded with A83-01 have improved potential for cell-therapies and regenerative medicine applications.
Overall design This data is RNA-seq of passaged 6 endometrial mesenchymal stem cells treated with DMSO control or 1mM A83-01. Each group has cells from six independent female donors (paired untreated/U and A83-01 treated/T1).
Contributor(s) Gurung S, Williams SM, Deane JA, Werkmeister JA, Gargett CE
Citation(s) 30564575
Submission date May 31, 2018
Last update date Dec 26, 2018
Contact name Shanti Gurung
Organization name Hudson Institute of Medical Research
Street address 27-31 Wright Street
City Clayton
State/province Vic
ZIP/Postal code Postal
Country Australia
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (12)
GSM3167454 eMSCs_U_S1
GSM3167455 eMSCs_U_S2
GSM3167456 eMSCs_U_S3
BioProject PRJNA473912
SRA SRP149417

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Supplementary file Size Download File type/resource
GSE115137_Gurung_Table_of_counts.txt.gz 648.6 Kb (ftp)(http) TXT
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Processed data are available on Series record

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