Lineage specification of human dendritic cells is marked by IRF8 expression in hematopoietic stem cells and multipotent progenitors

被引：93

作者：

Lee, Jaeyop ^{[1
]}

Zhou, Yu Jerry ^{[1
]}

Ma, Wenji ^{[2
,3
]}

Zhang, Wanwei ^{[1
]}

Aljoufi, Arafat ^{[1
]}

Luh, Thomas ^{[1
]}

Lucero, Kimberly ^{[1
]}

Liang, Deguang ^{[1
]}

Thomsen, Matthew ^{[4
]}

Bhagat, Govind ^{[4
]}

Shen, Yufeng ^{[2
,3
]}

Liu, Kang ^{[1
]}

机构：

[1] Columbia Univ, Dept Microbiol & Immunol, Med Ctr, New York, NY USA

[2] Columbia Univ, Dept Syst Biol, Med Ctr, New York, NY 10027 USA

[3] Columbia Univ, Dept Biomed Informat, Med Ctr, New York, NY 10027 USA

[4] Columbia Univ, Dept Pathol & Cell Biol, Med Ctr, New York, NY USA

来源：

NATURE IMMUNOLOGY | 2017年 / 18卷 / 08期

基金：

美国国家卫生研究院;

关键词：

COMMITMENT; BLOOD; IDENTIFICATION; MACROPHAGES; PRECURSORS; MAP;

D O I：

10.1038/ni.3789

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The origin and specification of human dendritic cells (DCs) have not been investigated at the clonal level. Through the use of clonal assays, combined with statistical computation, to quantify the yield of granulocytes, monocytes, lymphocytes and three subsets of DCs from single human CD34(+) progenitor cells, we found that specification to the DC lineage occurred in parallel with specification of hematopoietic stem cells (HSCs) to the myeloid and lymphoid lineages. This started as a lineage bias defined by specific transcriptional programs that correlated with the combinatorial 'dose' of the transcription factors IRF8 and PU.1, which was transmitted to most progeny cells and was reinforced by upregulation of IRF8 expression driven by the hematopoietic cytokine FLT3L during cell division. We propose a model in which specification to the DC lineage is driven by parallel and inheritable transcriptional programs in HSCs and is reinforced over cell division by recursive interactions between transcriptional programs and extrinsic signals.

引用

页码：877 / +

页数：15

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