Prolonged expression of c-fos suppresses cell cycle entry of dormant hematopoietic stem cells.

Abstract:

:The proto-oncogene c-fos was transiently upregulated in primitive hematopoietic stem (Lin-Sca-1(+)) cells stimulated with stem cell factor, interleukin-3 (IL-3), and IL-6. To investigate a role of the c-fos in hematopoietic stem cells, we used bone marrow (BM) cells from transgenic mice carrying the c-fos gene under the control of the interferon-alpha/beta-inducible Mx-promoter (Mx-c-fos), and fetal liver cells from c-fos-deficient mice. Prolonged expression of the c-fos in Lin-Sca-1(+) BM cells inhibited factor-dependent colony formation and hematopoiesis on a stromal cell layer by keeping them at G0/G1 phase of the cell cycle. These Lin-Sca-1(+) BM cells on a stromal layer entered into the cell cycle whenever exogenous c-fos was downregulated. However, ectopic c-fos did not perturb colony formation by Lin-Sca-1(+) BM cells after they entered the cell cycle. Furthermore, endogenous c-fos is not essential to cell cycle progression of hematopoietic stem cells because the factor-dependent and the stroma-dependent hematopoiesis by Lin-Sca-1(+) fetal liver cells from c-fos-deficient mice was not impaired. These results suggest that the c-fos induced in primitive hematopoietic stem cells negatively controls cell cycle progression and maintains them in a dormant state.

journal_name

Blood

journal_title

Blood

authors

Okada S,Fukuda T,Inada K,Tokuhisa T

subject

Has Abstract

pub_date

1999-02-01 00:00:00

pages

816-25

issue

3

eissn

0006-4971

issn

1528-0020

journal_volume

93

pub_type

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