Identification of clonogenic common Flt3+ M-CSFR+ plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow

Identification of clonogenic common Flt3+ M-CSFR+ plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow
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DOI:
10.1038/ni1518
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发表时间:
2007-11-01
期刊:
影响因子:
30.5
通讯作者:
Manz, Markus G.
Manz, Markus G.
中科院分区:
医学1区
文献类型:
--
作者:
Onai, Nobuyuki;Obata-Onai, Aya;Manz, Markus G.

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类造血组织浆细胞和常规树突状细胞(DC)从造血干细胞连续再生。浆细胞样和常规DC的细胞因子依赖性和生物学表明再生可能通过常见的DC限制性发育中间体进行。通过选择与DC发育相关的细胞因子受体表达,我们在此鉴定了在小鼠骨髓中具有不同基因表达谱的高度循环的Lin(-)c-Kit(int)Flt 3(+)M-CSFR+细胞,其在体外克隆水平上以及作为体外和体内的群体,有效地产生浆细胞样和常规DC,但没有其他谱系,其在体内注射细胞因子Flt 3配体后数量增加。因此,这些克隆形成的共同DC祖细胞定义了一个由精氨酸调节的DC发育途径,该途径确保了各种DC群体的供应。
Lymphoid tissue plasmacytoid and conventional dendritic cells (DCs) are continuously regenerated from hematopoietic stem cells. The cytokine dependence and biology of plasmacytoid and conventional DCs suggest that regeneration might proceed through common DC-restricted developmental intermediates. By selecting for cytokine receptor expression relevant to DC development, we identify here highly cycling Lin(-)c-Kit(int)Flt3(+)M-CSFR+ cells with a distinct gene-expression profile in mouse bone marrow that, on a clonal level in vitro and as a population both in vitro and in vivo, efficiently generated plasmacytoid and conventional DCs but no other lineages, which increased in number after in vivo injection of the cytokine Flt3 ligand. These clonogenic common DC progenitors thus define a cytokine-regulated DC developmental pathway that ensures the supply of various DC populations.