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PMID:20709909

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Citation

Ragu, C, Elain, G, Mylonas, E, Ottolenghi, C, Cagnard, N, Daegelen, D, Passegué, E, Vainchenker, W, Bernard, OA and Penard-Lacronique, V (2010) The transcription factor Srf regulates hematopoietic stem cell adhesion. Blood 116:4464-73

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.

Links

PubMed Online version:10.1182/blood-2009-11-251587

Keywords

Animals; Cell Adhesion; Cell Cycle; Cell Lineage; Gene Deletion; Gene Expression; Hematopoiesis; Hematopoietic Stem Cells/cytology; Hematopoietic Stem Cells/metabolism; Integrins/metabolism; Mice; Serum Response Factor/genetics; Serum Response Factor/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:SRF

acts_upstream_of_or_within

GO:0030220: platelet formation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2176073,MGI:MGI:3046779

P

Seeded From UniProt

complete

MOUSE:SRF

acts_upstream_of_or_within

GO:0002521: leukocyte differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2176073,MGI:MGI:3046779

P

Seeded From UniProt

complete

MOUSE:SRF

acts_upstream_of_or_within

GO:0007160: cell-matrix adhesion

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2176073,MGI:MGI:3046779

P

Seeded From UniProt

complete

MOUSE:SRF

acts_upstream_of_or_within

GO:0048821: erythrocyte development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2176073,MGI:MGI:3046779

P

Seeded From UniProt

complete

MOUSE:SRF

acts_upstream_of_or_within

GO:0060218: hematopoietic stem cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2176073,MGI:MGI:3046779

P

  • occurs_in:(EMAPA:32760)
  • results_in_acquisition_of_features_of:(CL:0000837)|occurs_in(EMAPA:32760)
  • results_in_acquisition_of_features_of:(CL:0000037)

Seeded From UniProt

complete

MOUSE:SRF

acts_upstream_of_or_within

GO:0035855: megakaryocyte development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2176073,MGI:MGI:3046779

P

Seeded From UniProt

complete


See also

References

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