Hematopoietic progenitor cell lines with myeloid and lymphoid potential.

Hematopoietic progenitor cell lines with myeloid and lymphoid potential.
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DOI:
10.1038/nmeth.2510
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发表时间:
2013-08
期刊:
影响因子:
48
通讯作者:
Haecker, Hans
Haecker, Hans
中科院分区:
生物学1区
文献类型:
--
作者:
Redecke, Vanessa;Wu, Ruiqiong;Zhou, Jingran;Finkelstein, David;Chaturvedi, Vandana;High, Anthony A.;Haecker, Hans

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免疫细胞分化和功能的研究受到合适的和可扩展的实验系统的缺点的限制。在这里,我们表明,雌激素调节形式的HOXB 8是逆转录病毒传递到小鼠骨髓细胞可以使用沿着与FLT 3配体有条件地永生化早期造血祖细胞(Hoxb 8-FL)。Hoxb 8-FL细胞丧失了自我更新能力和巨核细胞/红系细胞谱系潜能,但维持骨髓和淋巴潜能。Hoxb 8-FL细胞在体外和体内分化成不同的骨髓和淋巴样细胞类型,包括巨噬细胞、粒细胞、树突细胞和B-和T-淋巴细胞,其在表型和功能上与其原代对应物无法区分。定量体外细胞谱系潜能测定暗示Hoxb 8-FL细胞的髓样和B细胞潜能与初级淋巴致敏的多能祖细胞相当,而T细胞潜能相对降低。鉴于Hoxb 8-FL细胞的简单性和无限增殖能力,该系统为研究细胞分化和免疫细胞功能提供了独特的机会。
Investigation of immune cell differentiation and function is limited by shortcomings of suitable and scalable experimental systems. Here we show that an estrogen–regulated form of HOXB8 that is retrovirally delivered into mouse bone marrow cells can be used along with FLT3 ligand to conditionally immortalize early hematopoietic progenitor cells (Hoxb8–FL). Hoxb8–FL cells have lost self–renewal capacity and megakaryocyte/ erythroid lineage potential, but sustain myeloid and lymphoid potential. Hoxb8–FL cells differentiate in vitro and in vivo into different myeloid and lymphoid cell types, including macrophages, granulocytes, dendritic cells and B– and T–lymphocytes, which are phenotypically and functionally indistinguishable from their primary counterparts. Quantitative in vitro cell lineage potential assays implicate that myeloid and B–cell potential of Hoxb8–FL cells is comparable to primary lymphoid–primed multipotent progenitors, while T–cell potential is comparatively reduced. Given the simplicity and unlimited proliferative capacity of Hoxb8–FL cells, this system provides unique opportunities to investigate cell differentiation and immune cell functions.
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