Correlation of c-kit expression and cell cycle regulation by transforming growth factor-beta in CD34+ CD38- human bone marrow cells
Correlation of c-kit expression and cell cycle regulation by transforming growth factor-beta in CD34+ CD38- human bone marrow cells
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DOI：
10.1034/j.1600-0609.2003.00152.x
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发表时间：
2003-11-01
影响因子：
3.1
通讯作者：
Tanizawa, T
中科院分区：
文献类型：
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作者：
Morita, N;Yamamoto, M;Tanizawa, T
探讨c-kit表达与内源性转化生长因子-β调控细胞周期的关系将人骨髓造血祖细胞中的TGF-β、CD 34（+）CD 38（-）c-kit（低/-）和CD 34（+）CD 38（-）c-kit（高）群体在干细胞因子、血小板生成素、白细胞介素-3（IL-3）、IL-6、粒细胞集落刺激因子、粒细胞/巨噬细胞集落刺激因子和抗TGF-β，并分析细胞周期状态。G（0）/G（1）阻滞在预培养的CD 34（+）CD 38（-）c-kit（低/-）亚群中最为显著（95.62 +/- 4.15%）。而由CD 34（+）CD 38（-）c-kit（high）细胞起始的后培养的CD 34（+）CD 38（-）c-kit（high）细胞在36小时内进入细胞周期，从CD 34（+）CD 38（-）c-kit（低/-）细胞起始的后培养的CD 34（+）CD 38（-）c-kit（低/-）细胞保持休眠直至36小时，并在90小时内进入细胞周期。β-CD 34（+）CD 38（-）c-kit（high）细胞培养后S/G（2）M期细胞比例从19.08 ± 11.95增加到47.04 ± 2.93%，但对CD 34（+）CD 38（-）c-kit（low/-）细胞培养后S/G（2）M期细胞比例无明显影响。这些结果表明，内源性TGF-β在CD 34（+）CD 38（-）细胞中c-kit（高）而不是c-kit（低/-）细胞的细胞周期停滞中起重要作用，CD 34（+）CD 38（-）细胞增殖而不经历分化。CD 34（+）CD 38（-）c-kit（high）和CD 34（+）CD 38（-）c-kit（low/-）亚群进入细胞周期的不同调节机制可能是它们对内源性TGF-β敏感性不同的结果。
To investigate the relationship between c-kit expression and cell cycle regulation by endogenous transforming growth factor-beta (TGF-beta) in human bone marrow hematopoietic progenitor cells, CD34(+) CD38(-)c-kit(low/-) and CD34(+) CD38(-)c-kit(high) populations were cultured in stem cell factor, thrombopoietin, interleukin-3 (IL-3), IL-6, granulocyte colony-stimulating factor, granulocyte/macrophage colony-stimulating factor and anti-TGF-beta, and analyzed for cell cycle status. Arrest in G(0)/G(1) was most prominent in the precultured CD34(+) CD38(-)c-kit(low/-) subset (95.62 +/- 4.15%). While postcultured CD34(+) CD38(-)c-kit(high) cells initiated from CD34(+) CD38(-)c-kit(high) cells entered cell cycle within 36 hr, postcultured CD34(+) CD38(-)c-kit(low/-) cells initiated from CD34(+) CD38(-)c-kit(low/-) cells remained dormant until 36 hr and entered cell cycle within 90 hr. Anti-TGF-beta increased the percentage of S/G(2)M phase postcultured CD34(+) CD38(-)c-kit(high) cells (from 19.08 +/- 11.95 to 47.04 +/- 2.93%), but no significant change was observed in postcultured CD34(+) CD38(-)c-kit(low/-) cells. These results suggest that endogenous TGF-beta plays an important role in the cell cycle arrest of c-kit(high) but not c-kit(low/-) cells in CD34(+) CD38(-) cells, which proliferate without undergoing differentiation. The different regulatory mechanism of cell cycle entry of the CD34(+) CD38(-)c-kit(high) and CD34(+) CD38(-)c-kit(low/-) subsets might be the result of differences in their sensitivity to endogenous TGF-beta.