Abstract 16190: Master Cardiac Transcription Factor MESP1 is Highly Expressed in Adult Human CD34+ Hematopoietic Stem Cells and its Levels are Modulated by Body Mass Index
Background: Adult human CD34+ stem cells (SCs) differentiate to both blood and vascular cell lineages, and may have benefit in ischemic heart and limb disease. Given the similar differentiation potential of CD34+ SCs with embryonic hemangioblasts, the objective of our study was to determine if adult human CD34+ SCs utilize a similar molecular mechanism to differentiate as found in development.
Methods: Human CD34+ lin- SCs were sorted from bone marrow (BM), and peripheral blood (PB) mononuclear cells from twelve subjects without heart disease. Colony forming assays confirmed differentiation to blood lineages. Unsorted pBMNCs were retained as a non-stem cell, negative control. Total RNA was extracted from equal numbers of cells, and quantitative PCR (qPCR) for relative transcript expression. qPCR data was normalized to two invariant transcripts using the ΔΔCt method, and significant differences in transcript levels determined by ANOVA. Univariate analyses identified correlations in transcript level with clinical variables (age, sex, BMI, blood pressure), and significance determined by Pearson’s correlation.
Results: Transcript levels of CD34, CD133, TAL1/SCL and MIXL1 were present at 20 fold higher levels in CD34+ SCs from BM and PB relative to unsorted pBMNCs. VEGFR2, but not Neuropilin-1, was abundantly expressed (14 fold higher, p < 0.01) in both BM and PB CD34+ SCs. We found MESP1 was abundantly expressed in both BM and PB CD34+ SCs (5 fold greater, p < 0.001) relative to unsorted pBMNCs. Finally, body mass index, but not age, sex, or smoking, inversely correlated with MESP1 expression in CD34+ stem cells (r2=0.35, p < 0.025).
Conclusions: The master cardiac transcription factor MESP1 is abundantly expressed in adult human CD34+ stem cells, and MESP1 mRNA inversely correlates with body mass index. The findings represent novel evidence for the embryonic transcription factor MESP1 in the biology of adult human CD34+ SCs, and suggest obesity decreases MESP1 levels.
- © 2013 by American Heart Association, Inc.