Common fibroid-associated genes are altered between cell populations isolated from myometrium and fibroid tissues — ASN Events
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  3. Common fibroid-associated genes are altered between cell populations isolated from myometrium and fibroid tissues

Common fibroid-associated genes are altered between cell populations isolated from myometrium and fibroid tissues (#283)

Sarah J Holdsworth-Carson 1 , Marina Zaitseva 1 , Jane Girling 1 , Beverley J Vollenhoven 2 , Peter AW Rogers 1
  1. Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, VIC, Australia
  2. Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia

Background: Uterine fibroids are a common condition affecting reproductive-aged women. Multiple studies have identified differential gene expression between myometrium and fibroids. Although clonal in origin, multiple cell phenotypes exist in fibroids. We have recently developed methods to sort myometrium and fibroids into cell populations enriched for smooth muscle cells (SMC), vascular SMC, fibroblasts and fibroid-associated fibroblasts.
Objective: To investigate isolated cell populations from myometrium and fibroid to determine if these populations differ in expression of genes known to be associated with fibroids. To determine if gene expression is different between phenotypically different cell populations isolated from clonal fibroids.
Methods: Myometrium and fibroid were collected following hysterectomy. FACS was used to identify and isolate different cell sub-populations. CD31 and CD45 identified and excluded endothelial and leukocytes cells. CD90 and ALDH identified SMC and fibroblasts. Cells were separated into 4 sub-populations: ALDH-/CD90- (VSMC), ALDH-/CD90+(SMC), ALDH+/CD90+ (fibroblasts) and ALDH-/CD90+bright(fibroid fibroblasts). qRT-PCR for ERα, ERβ, PR, PRB, TGFB1, TGFB3, TGFBR1, TGFBR2 and CRABP2 gene expression was performed (n=13). Analysis was performed using non-parametric Kruskal-Wallis and Mann-Whitney-U tests (with Bonferroni correction).
Results: PR, PRB and CRABP2 mRNA expression were increased in ALDH-/CD90- and ALDH-/CD90+ populations from fibroids compared to myometrium. TGFBR2 mRNA was decreased in fibroid-derived ALDH-/CD90+ SMC compared to myometrium. ALDH+/CD90+ fibroblast gene expression was unchanged between myometrium and fibroids. Fibroid ALDH-/CD90+bright–fibroblasts were compared to fibroid ALDH+/CD90+ fibroblasts; CRABP2 mRNA expression was decreased in ALDH-/CD90+bright fibroblasts. Within the clonal fibroid, only ALDH+/CD90+ fibroblasts had increased CRAPB2 mRNA expression compared to ALDH-/CD90-, ALDH-/CD90+, and ALDH-/CD90+bright cells.
Conclusion: The expression of some fibroid-associated genes (CRABP2, PR, PRB, TGFBR2) is altered in phenotypically different cells isolated from fibroids and myometrium. This is the first demonstration of cell-specific differential expression of fibroid-associated genes, and opens the way for investigation of paracrine interactions between different fibroid cell types.

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