Glucocorticoid hormone-induced chromatin remodeling enhances human hematopoietic stem cell homing and engraftment

Bin Guo, Xinxin Huang, Scott Cooper, Hal E. Broxmeyer

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Efficient hematopoietic stem cell (HSC) homing is important for hematopoietic cell transplantation (HCT), especially when HSC numbers are limited, as in the use of cord blood (CB). In a screen of small-molecule compounds, we identified glucocorticoid (GC) hormone signaling as an activator of CXCR4 expression in human CB HSCs and hematopoietic progenitor cells (HPCs). Short-term GC pretreatment of human CB HSCs and HPCs promoted SDF-1-CXCR4-axis-mediated chemotaxis, homing, and long-term engraftment when these cells were transplanted into primary- and secondary-recipient NSG mice. Mechanistically, activated glucocorticoid receptor binds directly to a glucocorticoid response element in the CXCR4 promoter and recruits the SRC-1-p300 complex to promote H4K5 and H4K16 histone acetylation, facilitating transcription of CXCR4. These results suggest a new and readily available means to enhance the clinical efficacy of CB HCT.

Original languageEnglish (US)
Pages (from-to)424-428
Number of pages5
JournalNature Medicine
Volume23
Issue number4
DOIs
StatePublished - Apr 1 2017

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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