MiR-92a corrects CD34+ cell dysfunction in diabetes by modulating core circadian genes involved in progenitor differentiation

Ashay D. Bhatwadekar, Yuanqing Yan, Valerie Stepps, Sugata Hazra, Maria Korah, Stephen Bartelmez, Brahim Chaqour, Maria B. Grant*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Autologous CD34+ cells are widely used for vascular repair; however, in individuals with diabetes and microvascular disease these cells are dysfunctional. In this study, we examine expression of the clock genes Clock, Bmal, Per1, Per2, Cry1, and Cry2 in CD34+ cells of diabetic and nondiabetic origin and determine the small encoding RNA (miRNA) profile of these cells. The degree of diabetic retinopathy (DR) was assessed. As CD34+ cells acquired mature endothelial markers, they exhibit robust oscillations of clock genes. siRNA treatment of CD34+ cells revealed Per2 as the only clock gene necessary to maintain the undifferentiated state of CD34+ cells. Twenty-five miRNAs targeting clock genes were identified. Three of the miRNAs (miR-18b, miR-16, and miR-34c) were found only in diabetic progenitors. The expression of the Per2- regulatory miRNA, miR-92a, was markedly reduced in CD34+ cells from individuals with DR compared with control subjects and patients with diabetes with no DR. Restoration of miR-92a levels in CD34+ cells from patients with diabetes with DR reduced the inflammatory phenotype of these cells and the diabetes-induced propensity toward myeloid differentiation. Our studies suggest that restoring levels of miR-92a could enhance the usefulness of CD34+ cells in autologous cell therapy.

Original languageEnglish (US)
Pages (from-to)4226-4237
Number of pages12
Issue number12
StatePublished - Dec 2015
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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