HEMATOPOIESIS AND STEM CELLS The transcription factor Srf regulates hematopoietic stem cell adhesion

stem cells (HSCs) in the bone marrow (BM) niches control their migration and affect their cell-cycle dynamics. The se-rum response factor (Srf) regulates growth factor–inducible genes and genes controlling cytoskeleton structures in-volved in cell spreading, adhesion, and migration. We identified a role for Srf in HSC adhesion and steady-state hemato-poiesis. Conditional deletion of Srf in BM cells resulted in a 3-fold expansion of the long- and short-term HSCs and multipo-tent progenitors (MPPs), which occurs without long-term modification of cell-cycle dynamics. Early differentiation steps to myeloid and lymphoid lineages were normal, but Srf loss results in alterations in mature-cell production and severe thrombocytopenia. Srf-null BM cells also displayed compromised engraftment properties in transplantation assays. Gene expression analysis identified Srf target genes expressed in HSCs, including a network of genes associated with cell migration and adhesion. Srf-null stem cells and MPPs displayed impair expres-sion of the integrin network and de-creased adherence in vitro. In addition, Srf-null mice showed increase numbers of circulating stem and progenitor cells, which likely reflect their reduced reten-tion in the BM. Altogether, our results demonstrate that Srf is an essential regu-lator of stem cells and MPP adhesion, and suggest that Srf acts mainly through cell-matrix interactions and integrin signal-ing. (Blood. 2010;116(22):4464-4473