Perivascular human endometrial mesenchymal stem cells express pathways relevant to self-renewal, lineage specification, and functional phenotype

Trimble L B Spitzer, Angela Rojas, Zara Zelenko, Lusine Aghajanova, David Erikson, Fatima Barragan Meyer, John S. Tamaresis, Amy E. Hamilton, Juan C. Irwin, Linda C. Giudice

Research output: Contribution to journalArticle

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Abstract

Human endometrium regenerates on a cyclic basis from candidate stem/progenitors whose genetic programs are yet to be determined. A subpopulation of endometrial stromal cells, displaying key properties of mesenchymal stem cells (MSCs), has been characterized. The endometrial MSC (eMSC) is likely the precursor of the endometrial stromal fibroblast. The goal of this study was to determine the transcriptome and signaling pathways in the eMSC to understand its functional phenotype. Endometrial stromal cells from oocyte donors (n = 20) and patients undergoing benign gynecologic surgery (n = 7) were fluorescence-activated cell sorted into MCAM (CD146)+/DGFRB+ (eMSC), MCAM (CD146)-/PDGFRB+ (fibroblast), and MCAM (CD146)+/PDGFRB- (endothelial) populations. The eMSC population contained clonogenic cells with a mesenchymal phenotype differentiating into adipocytes when cultured in adipogenic medium. Gene expression profiling using Affymetrix Human Gene 1.0 ST arrays revealed 762 and 1518 significantly differentially expressed genes in eMSCs vs. stromal fibroblasts and eMSCs vs. endothelial cells, respectively. By principal component and hierarchical clustering analyses, eMSCs clustered with fibroblasts and distinctly from endothelial cells. Endometrial MSCs expressed pericyte markers and were localized by immunofluorescence to the perivascular space of endometrial small vessels. Endometrial MSCs also expressed genes involved in angiogenesis/vasculogenesis, steroid hormone/ypoxia responses, inflammation, immunomodulation, cell communication, and proteolysis/inhibition, and exhibited increased Notch, TGFB, IGF, Hedgehog, and G-protein-coupled receptor signaling pathways, characteristic of adult tissue MSC self-renewal and multipotency. Overall, the data support the eMSC as a clonogenic, multipotent pericyte that displays pathways of self-renewal and lineage specification, the potentialto respond to conditions during endometrial desquamation and regeneration, and a genetic program predictive of its differentiated lineage, the stromal fibroblast.

Original languageEnglish (US)
Article number58
JournalBiology of Reproduction
Volume86
Issue number2
DOIs
StatePublished - Feb 1 2012
Externally publishedYes

Fingerprint

Mesenchymal Stromal Cells
Fibroblasts
Phenotype
Platelet-Derived Growth Factor beta Receptor
Pericytes
Stromal Cells
Endothelial Cells
Hedgehog Proteins
Genes
Gynecologic Surgical Procedures
Immunomodulation
Gene Expression Profiling
G-Protein-Coupled Receptors
Endometrium
Transcriptome
Adipocytes
Cell Communication
Population
Proteolysis
Oocytes

Keywords

  • Cell fate
  • Endometrium
  • Immunomodulation
  • Mesenchymal stem cells
  • Microarray
  • Pathways
  • Pericytes
  • Self-renewal

ASJC Scopus subject areas

  • Cell Biology

Cite this

Perivascular human endometrial mesenchymal stem cells express pathways relevant to self-renewal, lineage specification, and functional phenotype. / Spitzer, Trimble L B; Rojas, Angela; Zelenko, Zara; Aghajanova, Lusine; Erikson, David; Meyer, Fatima Barragan; Tamaresis, John S.; Hamilton, Amy E.; Irwin, Juan C.; Giudice, Linda C.

In: Biology of Reproduction, Vol. 86, No. 2, 58, 01.02.2012.

Research output: Contribution to journalArticle

Spitzer, TLB, Rojas, A, Zelenko, Z, Aghajanova, L, Erikson, D, Meyer, FB, Tamaresis, JS, Hamilton, AE, Irwin, JC & Giudice, LC 2012, 'Perivascular human endometrial mesenchymal stem cells express pathways relevant to self-renewal, lineage specification, and functional phenotype', Biology of Reproduction, vol. 86, no. 2, 58. https://doi.org/10.1095/biolreprod.111.095885
Spitzer, Trimble L B ; Rojas, Angela ; Zelenko, Zara ; Aghajanova, Lusine ; Erikson, David ; Meyer, Fatima Barragan ; Tamaresis, John S. ; Hamilton, Amy E. ; Irwin, Juan C. ; Giudice, Linda C. / Perivascular human endometrial mesenchymal stem cells express pathways relevant to self-renewal, lineage specification, and functional phenotype. In: Biology of Reproduction. 2012 ; Vol. 86, No. 2.
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