Transcriptional changes in human haematopoietic stem and progenitor cells(HSPCs) from umbilical cord blood in response to the corticotropin releasing hormone(CRH)

Corticotrophin-releasing hormone (CRH) is a key regulator involved in the stress pathway, yet its functions in the direct regulation of human stem/ progenitor cells (HSPCs) are poorly understood. Here we report that human CD34+ HSPCs constitutively expressed CRH receptor1. Treatment with CRH increased the motility and deformability of human HSPCs. Intravital two-photon imaging of bone tissues showed that CRH stimulated migration and bone marrow homing of HSPCs in vivo. Pretreatment of human HSPCs promoted homing and long-term engraftment when transplanted into primary and secondary NSG mice. Mechanistically, CRH modulates cell mechanics by extracellular matrix (ECM) remodeling, correlating with increased expression of the ECM protein THBS2 and activities of the Rho family small GTPases. Collectively, these findings show that CRH, a neurotransmitter, regulates biomechanics, which is correlated with its new functions in HSPSs migration, homing and engraftment, designating CRH as a promising drug candidate to facilitate clinical HSC transplantation. Overall design: To explore the specific mechanism of CRH regulation of hematopoietic stem cells, we isolated and purified HSPCs derived from umbilical cord blood and treated them with CRH for 16 hours. We then performed gene expression profiling analysis using data obtained from RNA-seq of 4 different donors .Comparative gene expression profling analysis of RNA-seq data for freshly isolated HSPCs treat with or without CRH.