Distinct hematopoietic progenitor compartments are delineated by the expression of aldehyde dehydrogenase and CD34
Distinct hematopoietic progenitor compartments are delineated by the expression of aldehyde dehydrogenase and CD34
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DOI：
10.1182/blood-2004-09-3652
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发表时间：
2005-07-01
期刊：
影响因子：
20.3
通讯作者：
Smith, CA
中科院分区：
文献类型：
--
作者：
Storms, RW;Green, PD;Smith, CA
广泛的造血干细胞和祖细胞存在于脐带血（UCB）的一部分中，其表现出低光散射特性（SSC 10）和醛脱氢酶（ALDH（br））的高表达。许多SSCIO ALDH（br）细胞共表达CD 34;然而，其它细胞表达ALDH或CD 34。为了研究这些细胞亚群的发育潜力，在各种体内和体外试验中对纯化的ALDH（br）CD 34（+）、ALDH（neg）CD 34（+）和ALDH（br）CD 34（neg）UCB细胞进行了表征。在对非肥胖糖尿病/严重联合免疫缺陷（NOD/SCID）小鼠进行的长期和短期再增殖试验中，以及在原发性和继发性长期培养试验中，监测能够进行多谱系发育的原始祖细胞。这些祖细胞在ALDH（br）CD 34（+）部分中高度富集。该细胞组分还富集了体外检测到的短期髓样祖细胞。相比之下，ALDH（neg）CD 34（+）细胞含有很少的原始祖细胞，并具有减少的短期髓样潜能，但表现出增强的短期多系发育，在非肥胖糖尿病/严重联合免疫缺陷（NOD/SCID）小鼠的长期和短期再增殖试验中，以及在原代和二次长期培养试验中进行了监测。这些祖细胞在ALDH（br）CD 34（+）部分中高度富集。该细胞组分还富集了体外检测到的短期髓样祖细胞。相比之下，ALDH（neg）CD 34（+）细胞含有很少的原始祖细胞，并具有减少的短期髓样潜能，但在体外显示出增强的短期自然杀伤（NK）细胞发育。ALDH（br）CD 34（neg）细胞未得到所用任何试验的有效支持。这些研究表明，特别是ALDH的表达划定了不同的CD 34（+）干细胞和祖细胞区室。ALDH的差异表达可能提供一种手段来探索与骨髓和淋巴发育相关的正常和恶性过程。
A broad range of hematopoietic stem cells and progenitors reside within a fraction of umbilical cord blood (UCB) that exhibits low light scatter properties (SSCIo) and high expression of aldehyde dehydrogenase (ALDH(br)). Many SSCIo ALDH(br) cells coexpress CD34; however, other cells express either ALDH or CD34. To investigate the developmental potential of these cell subsets, purified ALDH(br) CD34(+), ALDH(neg) CD34(+) and ALDH(br) CD34(neg) UCB cells were characterized within a variety of in vivo and in vitro assays. Primitive progenitors capable of multilineage development were monitored in long- and short-term repopulation assays performed on nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice, and in primary and secondary long-term culture assays. These progenitors were highly enriched within the ALDH(br) CD34(+) fraction. This cell fraction also enriched short-term myeloid progenitors that were detected in vitro. By comparison, ALDH(neg) CD34(+) cells contained few primitive progenitors and had diminished short-term myeloid potential but exhibited enhanced short-multilineage development were monitored in long- and short-term repopulation assays performed on nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice, and in primary and secondary long-term culture assays. These progenitors were highly enriched within the ALDH(br) CD34(+) fraction. This cell fraction also enriched short-term myeloid progenitors that were detected in vitro. By comparison, ALDH(neg) CD34(+) cells contained few primitive progenitors and had diminished short-term myeloid potential but exhibited enhanced short-term natural killer (NK) cell development in vitro. The ALDH(br) CD34(neg) cells were not efficiently supported by any of the assays used. These studies suggested that in particular the expression of ALDH delineated distinct CD34(+) stem cell and progenitor compartments. The differential expression of ALDH may provide a means to explore normal and malignant processes associated with myeloid and lymphoid development.