Identification of a Novel Subpopulation of Human Cord Blood CD34−CD133−CD7−CD45+Lineage− Cells Capable of Lymphoid/NK Cell Differentiation After In Vitro Exposure to IL-15 1
Identification of a Novel Subpopulation of Human Cord Blood CD34−CD133−CD7−CD45+Lineage− Cells Capable of Lymphoid/NK Cell Differentiation After In Vitro Exposure to IL-15 1
复制标题
体外暴露于 IL-15 后能够分化为淋巴细胞/NK 细胞的人脐带血 CD34−CD133−CD7−CD45+谱系−细胞新亚群的鉴定 1
作者：
S. Rutella;G. Bonanno;M. Marone;D. D. De Ritis;A. Mariotti;M. Voso;G. Scambia;S. Mancuso;G. Leone;L. Pierelli
造血干细胞 (HSC) 区室包含具有异质增殖和发育潜力的细胞亚群。人类脐带血 (UCB) 中已描述和表征了许多可能比 CD34+ HSC 处于分化早期阶段的 CD34− 细胞亚群。我们鉴定了人 UCB 中包含的 CD34−CD133−CD7−CD45dimlineage (lin)− HSC 的新亚群，其具有较低但可测量的长期培养起始细胞活性。 CD34−CD133−CD7−CD45dimlin− HSC 暴露于干细胞因子可保留细胞活力，并与以下因素相关：1) 干细胞相关 Ags CD34 和 CD133 的一致表达，2) CFU 粒细胞巨噬细胞、突发形成单位红细胞和巨核细胞聚集体的生成，3) 显着延长的长期培养起始细胞活性，以及4) 髓过氧化物酶mRNA信号的上调。与 CD34+lin− 细胞不同，CD34−CD133−CD7−CD45dimlin− HSC 维持在 IL-15 条件下，但不维持在 IL-2 或 IL-7 条件下，可剧烈增殖并分化为 CD7+CD45brightCD25+CD44+ 淋巴祖细胞的同质群体，且高表达 T 细胞相关转录因子 GATA-3。尽管它们含有非克隆重排的 TCRγ 基因，但 IL-15 引发的 CD34−CD133−CD7−CD45dimlin− HSC 未能完全成熟，如其 CD3−TCRαβ−γδ− 表型所示。相反，添加 IL-15 的基质细胞培养与 NK 细胞表型和功能特征的获得相关。总的来说，来自人 UCB 的 CD34−CD133−CD7−CD45dimlin− HSC 对 IL-15 表现出极高的敏感性，并分化为淋巴细胞/NK 细胞。具有T/NK细胞分化潜能的CD34−lin− HSC移植是否会影响HSC移植治疗自身免疫或恶性疾病后的免疫重建和微小残留病的控制仍有待确定。
The hemopoietic stem cell (HSC) compartment encompasses cell subsets with heterogeneous proliferative and developmental potential. Numerous CD34− cell subsets that might reside at an earlier stage of differentiation than CD34+ HSCs have been described and characterized within human umbilical cord blood (UCB). We identified a novel subpopulation of CD34−CD133−CD7−CD45dimlineage (lin)− HSCs contained within human UCB that were endowed with low but measurable extended long-term culture-initiating cell activity. Exposure of CD34−CD133−CD7−CD45dimlin− HSCs to stem cell factor preserved cell viability and was associated with the following: 1) concordant expression of the stem cell-associated Ags CD34 and CD133, 2) generation of CFU-granulocyte-macrophage, burst-forming unit erythroid, and megakaryocytic aggregates, 3) significant extended long-term culture-initiating cell activity, and 4) up-regulation of mRNA signals for myeloperoxidase. At variance with CD34+lin− cells, CD34−CD133−CD7−CD45dimlin− HSCs maintained with IL-15, but not with IL-2 or IL-7, proliferated vigorously and differentiated into a homogeneous population of CD7+CD45brightCD25+CD44+ lymphoid progenitors with high expression of the T cell-associated transcription factor GATA-3. Although they harbored nonclonally rearranged TCRγ genes, IL-15-primed CD34−CD133−CD7−CD45dimlin− HSCs failed to achieve full maturation, as manifested in their CD3−TCRαβ−γδ− phenotype. Conversely, culture on stromal cells supplemented with IL-15 was associated with the acquisition of phenotypic and functional features of NK cells. Collectively, CD34−CD133−CD7−CD45dimlin− HSCs from human UCB displayed an exquisite sensitivity to IL-15 and differentiated into lymphoid/NK cells. Whether the transplantation of CD34−lin− HSCs possessing T/NK cell differentiation potential may impact on immunological reconstitution and control of minimal residual disease after HSC transplantation for autoimmune or malignant diseases remains to be determined.
登录
查看更多内容
DOI：
10.1056/nejm200205023461815
发表时间：
2002-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
G. Spangrude;B. Torok-Storb;M. Little
通讯作者：
G. Spangrude;B. Torok-Storb;M. Little
影响因子：
20.3
作者：
Sato, T;Laver, JH;Ogawa, M
通讯作者：
Ogawa, M
人骨髓 CD34- 细胞在体内移植并经历多谱系表达，包括产生 CD34- 细胞。
DOI：
--
发表时间：
1998
期刊：
Experimental hematology.
影响因子：
--
作者：
Zanjani,ED;Almeida-Porada,G;Livingston,AG;Flake,AW;Ogawa,M
通讯作者：
Ogawa,M
影响因子：
20.3
作者：
Hao, QL;Zhu, J;Crooks, GM
通讯作者：
Crooks, GM