Abstract:
:The mechanisms underlying granulocyte-colony stimulating factor (G-CSF)-induced mobilization of granulocytic lineage cells from the bone marrow to the peripheral blood remain elusive. We provide evidence that the transcriptional repressor growth factor independence-1 (Gfi-1) is involved in G-CSF-induced mobilization of granulocytic lineage cells from the bone marrow to the peripheral blood. We show that in vitro and in vivo G-CSF promotes expression of Gfi-1 and down-regulates expression of CXCR4, a chemokine receptor essential for the retention of hematopoietic stem cells and granulocytic cells in the bone marrow. Gfi-1 binds to DNA sequences upstream of the CXCR4 gene and represses CXCR4 expression in myeloid lineage cells. As a consequence, myeloid cell responses to the CXCR4 unique ligand SDF-1 are reduced. Thus, Gfi-1 not only regulates hematopoietic stem cell function and myeloid cell development but also probably promotes the release of granulocytic lineage cells from the bone marrow to the peripheral blood by reducing CXCR4 expression and function.
journal_name
Bloodjournal_title
Bloodauthors
De La Luz Sierra M,Gasperini P,McCormick PJ,Zhu J,Tosato Gdoi
10.1182/blood-2007-03-081448subject
Has Abstractpub_date
2007-10-01 00:00:00pages
2276-85issue
7eissn
0006-4971issn
1528-0020pii
blood-2007-03-081448journal_volume
110pub_type
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