title: The transcription factor Srf regulates hematopoietic stem cell adhesion.
abstract: Adhesion properties of hematopoietic stem cells (HSCs) in the bone marrow (BM) niches control their migration and affect their cell-cycle dynamics. The serum response factor (Srf) regulates growth factor-inducible genes and genes controlling cytoskeleton structures involved in cell spreading, adhesion, and migration. We identified a role for Srf in HSC adhesion and steady-state hematopoiesis. Conditional deletion of Srf in BM cells resulted in a 3-fold expansion of the long- and short-term HSCs and multipotent 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 expression of the integrin network and decreased adherence in vitro. In addition, Srf-null mice showed increase numbers of circulating stem and progenitor cells, which likely reflect their reduced retention in the BM. Altogether, our results demonstrate that Srf is an essential regulator of stem cells and MPP adhesion, and suggest that Srf acts mainly through cell-matrix interactions and integrin signaling.
authors: Inserm, U985, IGR, Villejuif, France.
authors: Christine
authors: C
authors: Ragu
authors: Gaelle
authors: G
authors: Elain
authors: Elena
authors: E
authors: Mylonas
authors: Chris
authors: C
authors: Ottolenghi
authors: Nicolas
authors: N
authors: Cagnard
authors: Dominique
authors: D
authors: Daegelen
authors: Emmanuelle
authors: E
authors: Passegué
authors: William
authors: W
authors: Vainchenker
authors: Olivier A
authors: OA
authors: Bernard
authors: Virginie
authors: V
authors: Penard-Lacronique
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002453:Cell Cycle; D019070:Cell Lineage; D017353:Gene Deletion; D015870:Gene Expression; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D051379:Mice; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D016023:Integrins; D026362:Serum Response Factor