Molecular mechanism of transforming growth factor β-mediated cell-cycle modulation in primary human CD34+ progenitors

Mo A. Dao, Joseph Hwa, Jan Nolta

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The mechanisms by which transforming growth factor β (TGF-β) 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-β 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-β antibody. Administration of TGF-β 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-β antibody. Neutralization of TGF-β 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-β.

Original languageEnglish (US)
Pages (from-to)499-506
Number of pages8
JournalBlood
Volume99
Issue number2
DOIs
StatePublished - Jan 15 2002
Externally publishedYes

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Transforming Growth Factors
Cell Cycle
Cells
Modulation
Cytokines
Hematopoietic Stem Cells
Stem cells
Cyclin-Dependent Kinase Inhibitor p15
Cyclin D2
Retinoblastoma Protein
Heterologous Transplantation
Phosphorylation
Antibodies
Cell Transplantation
Myeloid Cells
Assays
B-Lymphocytes
Stem Cells
T-Lymphocytes
Proteins

ASJC Scopus subject areas

  • Hematology

Cite this

Molecular mechanism of transforming growth factor β-mediated cell-cycle modulation in primary human CD34+ progenitors. / Dao, Mo A.; Hwa, Joseph; Nolta, Jan.

In: Blood, Vol. 99, No. 2, 15.01.2002, p. 499-506.

Research output: Contribution to journalArticle

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