Single adult human CD34+/Lin-/CD38- progenitors give rise to natural killer cells, B-lineage cells, dendritic cells, and myeloid cells
Single adult human CD34+/Lin-/CD38- progenitors give rise to natural killer cells, B-lineage cells, dendritic cells, and myeloid cells
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DOI：
10.1182/blood.v93.1.96.401k13_96_106
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发表时间：
1999-01-01
期刊：
影响因子：
20.3
通讯作者：
Moore, KA
中科院分区：
文献类型：
--
作者：
Miller, JS;McCullar, V;Moore, KA
骨髓基质培养物支持成人CD 34（+）/Lin（-）/HLA-DR-或CD 34（+）/Lin（-）/CD 38（-）细胞分化为自然杀伤（NK）或髓样细胞，但与定向淋巴祖细胞（CD 34（+）/Lin（-）/CD 45 RA（+）/CD 10（+））不同，不产生B细胞。我们测试了不同的微环境是否可以在NK细胞和B细胞谱系之间建立发育联系。将祖细胞与白细胞介素-7（IL-7）、flt 3配体（FL）、c-kit配体（KL）、IL-3、IL-2和AFT 024（一种支持可移植小鼠干细胞培养的小鼠胎肝细胞系）进行有限稀释培养。NK细胞、CD 10（+）/CD 19（+）B系细胞和树突状细胞（DC）从相同的起始群体发育，并且在该过程中需要IL-7、FL和KL。用IL-7、FL、KL、IL-2和IL-3将3，872个CD 34（+）/Lin（-）/CD 38（-）细胞单细胞沉积到AFT 024上，显示在培养起始时一次性添加IL-3对于单细胞的多谱系分化是必需的。经常检测到单和双谱系后代，但更重要的是，2%的单细胞可以产生至少三个谱系（NK细胞，B-谱系细胞和DC或骨髓细胞），提供直接证据表明NK和B-谱系分化来自相同条件下的共同淋巴骨髓造血祖细胞。这项研究为微环境生态位的作用提供了新的见解，微环境生态位控制着淋巴发育中最早的事件。(C)1999年，美国血液学会。
Marrow stromal cultures support adult CD34(+)/Lin(-)/HLA-DR- or CD34(+)/Lin(-)/CD38(-) cell differentiation into natural killer (NK) or myeloid cells, but unlike committed lymphoid progenitors (CD34(+)/Lin(-)/CD45RA(+)/CD10(+)), no B cells are generated. We tested whether different microenvironments could establish a developmental link between the NK and B-cell lineages. Progenitors were cultured in limiting dilutions with interleukin-7 (IL-7), flt3 ligand (FL), c-kit ligand (KL), IL-3, IL-2, and AFT024, a murine fetal liver line, which supports culture of transplantable murine stem cells. NK cells, CD10(+)/CD19(+) B-lineage cells and dendritic cells (DC) developed from the same starting population and IL-7, FL, and KL were required in this process. Single cell deposition of 3,872 CD34(+)/Lin(-)/CD38(-) cells onto AFT024 with IL-7, FL, KL, IL-2, and IL-3 showed that a one time addition of IL-3 at culture initiation was essential for multilineage differentiation from single cells. Single and double lineage progeny were frequently detected, but more importantly, 2% of single cells could give rise to at least three lineages (NK cells, B-lineage cells, and DC or myeloid cells) providing direct evidence that NK and B-lineage differentiation derive from a common lymphomyeloid hematopoietic progenitor under the same conditions. This study provides new insights into the role of the microenvironment niche, which governs the earliest events in lymphoid development. (C) 1999 by The American Society of Hematology.