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| Status |
Public on Nov 14, 2011 |
| Title |
Perivascular Human Endometrial Mesenchymal Stem Cells Express Pathways Relevant to Self-Renewal, Lineage Specification, and Functional Phenotype |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
A population of endometrial cells displaying key properties of mesenchymal stem cells (eMSC) has been identified in human endometrium. eMSC co-express CD146 and PDGFRB surface markers, have a perivascular location, and likely represent the reservoir of progenitors giving rise to the endometrial stromal fibroblast lineage. Endometrial stromal cells isolated from 16 oocyte donors and 3 benign gynecologic surgery subjects were FACS sorted into four populations: CD146+/PDGFRB+ (eMSC); CD146+/PDGFRB- (endothelial cells); CD146-/PDGFRB+ (stromal fibroblasts); CD146-/PDGFRB- (mixed population) then subjected to gene expression analysis on Affymetrix Human Gene 1.0 ST arrays, and differentially expressed genes compared between eMSC, stromal fibroblast, and endothelial cell populations. Ninety-two genes were validated by multiplex quantitative RT-PCR on seventy of these sorted cell populations. Immunohistochemistry was used to verify the perivascular location of eMSCs.Principal component analysis and hierarchical clustering showed eMSC clustering discretely near stromal fibroblasts and separately from endothelial cells. eMSC expressed pericyte markers and genes involved hypoxia response, inflammation, proteolysis, and angiogenesis/vasculogenesis – all relevant to endometrial tissue breakdown and regeneration. Additionally, eMSC displayed distinct gene profiles for cell-cell communication and regulation of gene expression. Overall, the phenotype of the eMSC is that of a multipotent pericyte responsive to hypoxic, proteolytic, and inflammatory stimuli, able to induce angiogenesis, migrate and differentiate into lineage cells, and potentially respond to estradiol and progesterone. Identifying the pathways and gene families described herein in the context of the endometrial niche, will be valuable in understanding normal and abnormal endometrial development in utero and differentiation in adult uterus.
The multipotent, perivascular endometrial mesenchymal stem cell has a “niche phenotype” of high Notch, TGFB, IGF, and Hedgehog and low canonical/non-canonical Wnt and EGF signaling.
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| Overall design |
Oocyte donors with no known uterine pathology underwent endometrial biopsy at the time of oocyte retrieval, following comparable GnHR agonist downregulated ovarian stimulation protocols. Tissue was digested and stromal cells isolated and sorted based on expression of CD146 and PDGFRB. RNA was extracted and hybridized on Affymetrix microarrays. Resulting data were compared between sorted isolated cell populations.
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| Contributor(s) |
Spitzer TL, Zelenko Z, Aghajanova L, Rojas A, Erikson D, Barragan F, Hamilton AE, Meyer M, Irwin JC, Giudice LC |
| Citation(s) |
22075475 |
| Submission date |
Aug 02, 2011 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Linda Giudice |
| E-mail(s) |
giudice@obgyn.ucsf.edu
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| Phone |
415-476-2039
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| Organization name |
University of California, San Francisco
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| Department |
OBGYN and RS
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| Lab |
Giudice Lab
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| Street address |
513 Parnassus Ave. HSE 1619
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94122 |
| Country |
USA |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (15)
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| GSM771056 |
Endometrial biopsy_ETB60_CD146+/PDGFRB+ |
| GSM771057 |
Endometrial biopsy_ETB60_CD146+/PDGFRB- |
| GSM771058 |
Endometrial biopsy_ETB60_CD146-/PDGFRB+ |
| GSM771059 |
Endometrial biopsy_ETB61_CD146+/PDGFRB+ |
| GSM771060 |
Endometrial biopsy_ETB61_CD146+/PDGFRB- |
| GSM771061 |
Endometrial biopsy_ETB61_CD146-/PDGFRB+ |
| GSM771062 |
Endometrial biopsy_ETB65_CD146+/PDGFRB+ |
| GSM771063 |
Endometrial biopsy_ETB65_CD146+/PDGFRB- |
| GSM771064 |
Endometrial biopsy_ETB65_CD146-/PDGFRB+ |
| GSM771065 |
Endometrial biopsy_ETB67_CD146+/PDGFRB+ |
| GSM771066 |
Endometrial biopsy_ETB67_CD146+/PDGFRB- |
| GSM771067 |
Endometrial biopsy_ETB67_CD146-/PDGFRB+ |
| GSM771068 |
Endometrial biopsy_ETB74_CD146+/PDGFRB+ |
| GSM771069 |
Endometrial biopsy_ETB74_CD146+/PDGFRB- |
| GSM771070 |
Endometrial biopsy_ETB74_CD146-/PDGFRB+ |
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| Relations |
| BioProject |
PRJNA144817 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE31152_RAW.tar |
63.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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