Molecular mechanism of transforming growth factor beta-mediated cell-cycle modulation in primary human CD34(+) progenitors.

Abstract:

:The mechanisms by which transforming growth factor beta (TGF-beta) exerts a negative effect on cell-cycle entry in primary human hematopoietic stem/progenitor cells were examined at the molecular and cellular levels. After treatment of primary human CD34+ progenitors with TGF-beta there was a decrease in the levels of cyclin D2 protein and an increase in levels of the cyclin-dependent kinase inhibitor (CDKI) p15 as compared to the levels in untreated cells. The converse was true after addition of neutralizing anti-TGF-beta antibody. Administration of TGF-beta to CD34+ cells in the presence of cytokines prevented retinoblastoma protein (pRb) phosphorylation, which occurred in the same cells treated with cytokines alone or cytokines and anti-TGF-beta antibody. Neutralization of TGF-beta during 24 to 48 hours of culture with cytokines significantly increased the number of colony-forming progenitors, but did not modulate the human stem cell pool, as measured in 6- to 12-month xenotransplantation assays. Equivalent numbers of human B, T, and myeloid cells were obtained after transplantation of cells treated with or without neutralization of TGF-beta.

journal_name

Blood

journal_title

Blood

authors

Dao MA,Hwa J,Nolta JA

doi

10.1182/blood.v99.2.499

subject

Has Abstract

pub_date

2002-01-15 00:00:00

pages

499-506

issue

2

eissn

0006-4971

issn

1528-0020

journal_volume

99

pub_type

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