Identification of a novel, human multilymphoid progenitor in cord blood

Identification of a novel, human multilymphoid progenitor in cord blood
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DOI:
10.1182/blood.v97.12.3683
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发表时间:
2001-06-15
期刊:
影响因子:
20.3
通讯作者:
Crooks, GM
Crooks, GM
中科院分区:
医学1区
文献类型:
--
作者:
Hao, QL;Zhu, J;Crooks, GM

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人类多能造血干细胞的淋巴定型的最早阶段尚未确定。鉴定出CD34(+)CD38(-)脐带血细胞的克隆形成亚群,其表达高水平的CD7抗原并且仅具有淋巴潜能。 CD34(+)CD38(-)CD7(+)(CD7(+))细胞均匀共表达CD45RA和HLA-DR; c-kit和Thy-1表达缺失至低水平。克隆分析表明,单个CD7(+)细胞可以产生B细胞、自然杀伤细胞和树突状细胞,但缺乏骨髓或红细胞潜能。相比之下,对照CD34(+)CD38(-)CD7(-)(CD7(-))细胞同时产生淋巴样细胞和骨髓红细胞。CD7(+)细胞的淋巴样潜能(在散装和单细胞培养物中产生淋巴样后代)与多能CD7(-)细胞相当。 RNA表达研究表明CD7(+)细胞表达PU.1和GATA-3,但不表达Pax-5、末端脱氧核苷酸转移酶或CD3ε。与之前描述的小鼠共同淋巴祖细胞相反,通过荧光激活细胞分选分析或 CD7(+) 细胞中的 RNA 聚合酶链反应未检测到白细胞介素 7 受体的 α 链。这些研究鉴定出具有 B 细胞和自然杀伤细胞谱系潜力的克隆性淋巴祖细胞,其分子谱表明其发育阶段比之前鉴定的淋巴祖细胞更原始。 CD7(+)表型将人类原始淋巴祖细胞与多能干细胞区分开来,从而可以研究早期人类淋巴细胞生成的调节,并为基因操作和移植提供多能干细胞的替代方案。 (C) 2001 年,美国血液学会。
The earliest stages of lymphoid commitment from human pluripotent hematopoietic stem cells have not been defined. A clonogenic subpopulation of CD34(+)CD38(-) cord blood cells were identified that expressed high levels of the CD7 antigen and possessed only lymphoid potential. CD34(+)CD38(-)CD7(+) (CD7(+)) cells uniformly coexpressed CD45RA and HLA-DR; c-kit and Thy-1 expression was absent to low. Clonal analysis demonstrated that single CD7(+) cells could generate B cells, natural killer cells, and dendritic cells but were devoid of myeloid or erythroid potential. In contrast, control CD34(+)CD38(-)CD7(-) (CD7(-)) cells generated both lymphoid and myelo-erythroid cells, The lymphoid potential (generation of lymphoid progeny in bulk and single cell cultures) of CD7(+) cells was equivalent to that of the pluripotent CD7(-) cells. RNA expression studies showed that CD7(+) cells expressed PU.1 and GATA-3, but did not express Pax-5, terminal deoxynucleotide transferase, or CD3 epsilon. In contrast to the previously described murine common lymphoid progenitor, the alpha chain of the receptor for interleukin-7 was not detected by fluorescence-activated cell sorting analysis or RNA polymerase chain reaction in CD7(+) cells. These studies identify a clonogenic lymphoid progenitor with both B-cell and natural killer cell lineage potential with a molecular profile that suggests a developmental stage more primitive than previously identified lymphoid progenitors. The CD7(+) phenotype distinguishes primitive human lymphoid progenitors from pluripotent stem cells, thus allowing the study of regulation of early human lymphopoiesis and providing an alternative to pluripotent stem cells for genetic manipulation and transplantation. (C) 2001 by The American Society of Hematology.