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 language | English (US) |
|---|---|
| Pages (from-to) | 499-506 |
| Number of pages | 8 |
| Journal | Blood |
| Volume | 99 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 15 2002 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Hematology
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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 journal › Article
}
TY - JOUR
T1 - Molecular mechanism of transforming growth factor β-mediated cell-cycle modulation in primary human CD34+ progenitors
AU - Dao, Mo A.
AU - Hwa, Joseph
AU - Nolta, Jan
PY - 2002/1/15
Y1 - 2002/1/15
N2 - 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.
AB - 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.
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U2 - 10.1182/blood.V99.2.499
DO - 10.1182/blood.V99.2.499
M3 - Article
VL - 99
SP - 499
EP - 506
JO - Blood
JF - Blood
SN - 0006-4971
IS - 2
ER -