STEM-CELL FACTOR RETARDS DIFFERENTIATION OF NORMAL HUMAN ERYTHROID PROGENITOR CELLS WHILE STIMULATING PROLIFERATION
STEM-CELL FACTOR RETARDS DIFFERENTIATION OF NORMAL HUMAN ERYTHROID PROGENITOR CELLS WHILE STIMULATING PROLIFERATION
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DOI：
10.1182/blood.v86.2.572.bloodjournal862572
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发表时间：
1995-07-15
期刊：
影响因子：
20.3
通讯作者：
DAI, CH
中科院分区：
文献类型：
--
作者：
MUTA, K;KRANTZ, SB;DAI, CH
干细胞因子（SCF）是c-kit酪氨酸激酶受体的配体，在体外能显著刺激红系祖细胞的聚集。我们现在报道了SCF延迟单个红系祖细胞的后代中的红系分化，同时大大增加这些后代的增殖，这些作用似乎与维持细胞活力的作用无关。高度纯化的第6天红系集落形成细胞（ECFC），主要由红系集落形成单位（CFU-E）组成，从人外周血红系爆发形成单位（BFU-E）产生。添加SCF的ECFC在无血清的液体培养，连同促红细胞生成素（EP）和胰岛素样生长因子1（IGF-1），导致DNA合成的显着增加，与细胞联苯胺阳性的延迟峰值和延迟掺入的Fe-59到血红蛋白相比，无SCF的文化。在SCF的存在下，ECFC的数量在此培养期间大大增加，联苯胺阳性细胞的总产量和血红蛋白的合成最终增加。为了确定SCF对单个ECFC的影响，在半固体和液体培养基中进行单细胞培养。这些培养物表明，SCF，在EP和IGF-1的存在下，作用于单个细胞和它们的后代，以延迟红细胞分化，同时显著刺激细胞增殖，而不增强初始细胞的活力。当使用来源于单一BFU-E的ECFC克隆测定SCF的作用时，这也是明显的。我们的实验表明，SCF作用于个体第6天的ECFC，以延缓红系细胞分化，同时通过明显独立于对细胞活力或程序性细胞死亡的影响的过程提供增强的增殖。(C)1995年，美国血液学会。
Stem cell factor (SCF), the ligand for the c-kit tyrosine kinase receptor, markedly stimulates the accumulation of erythroid progenitor cells in vitro. We now report that SCF delays erythroid differentiation among the progeny of individual erythroid progenitors while greatly increasing the proliferation of these progeny, These effects appear to be independent of an effect on maintenance of cell viability, Highly purified day-6 erythroid colony-forming cells (ECFC), consisting mainly of colony-forming units-erythroid (CFU-E), were generated from human peripheral blood burst-forming units-erythroid (BFU-E). Addition of SCF to the ECFC in serum-free liquid culture, together with erythropoietin (EP) and insulin-like growth factor 1 (IGF-1), resulted in a marked increase in DNA synthesis, associated with a delayed peak in cellular benzidine positivity and a delayed incorporation of Fe-59 into hemoglobin compared with cultures without SCF. In the presence of SCF, the number of ECFC was greatly expanded during this culture period, and total production of benzidine-positive cells plus hemoglobin synthesis were ultimately increased, To determine the effect of SCF on individual ECFC, single-cell cultures were performed in both semisolid and liquid media. These cultures demonstrated that SCF, in the presence of EP and IGF-1, acted on single cells and their descendants to delay erythroid differentiation while substantially stimulating cellular proliferation, without an enhancement of viability of the initial cells. This was also evident when the effect of SCF was determined using clones of ECFC derived from single BFU-E. Our experiments demonstrate that SCF acts on individual day-6 ECFC to retard erythroid differentiation while simultaneously providing enhanced proliferation by a process apparently independent of an effect on cell viability or programmed cell death. (C) 1995 by The American Society of Hematology.