Macrophage development from HSCs requires PU.1-coordinated microRNA expression

被引：99

作者：

Ghani, Saeed ^{[1
]}

Riemke, Pia ^{[1
]}

Schoenheit, Joerg ^{[1
]}

Lenze, Dido ^{[2
]}

Stumm, Juergen ^{[1
]}

Hoogenkamp, Maarten ^{[3
]}

Lagendijk, Anne ^{[4
,5
]}

Heinz, Sven ^{[6
]}

Bonifer, Constanze ^{[3
]}

Bakkers, Jeroen ^{[4
,5
]}

Abdelilah-Seyfried, Salim ^{[1
]}

Hummel, Michael ^{[2
]}

Rosenbauer, Frank ^{[1
]}

机构：

[1] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany

[2] Charite, Inst Pathol, D-13353 Berlin, Germany

[3] Univ Leeds, Leeds Inst Mol Med, Leeds, W Yorkshire, England

[4] KNAW, Dept Cellular & Mol Med, Hubrecht Inst, Utrecht, Netherlands

[5] Univ Med Ctr, Utrecht, Netherlands

[6] Univ Calif San Diego, La Jolla, CA 92093 USA

来源：

BLOOD | 2011年 / 118卷 / 08期

关键词：

HEMATOPOIETIC STEM-CELLS; TRANSCRIPTION FACTORS; IN-VIVO; ZEBRAFISH; PU.1; DIFFERENTIATION; LEUKEMIA; LINEAGE; IDENTIFICATION; MIR-146A;

D O I：

10.1182/blood-2011-02-335141

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

The differentiation of HSCs into myeloid lineages requires the transcription factor PU.1. Whereas PU.1-dependent induction of myeloid-specific target genes has been intensively studied, negative regulation of stem cell or alternate lineage programs remains incompletely characterized. To test for such negative regulatory events, we searched for PU.1-controlled microRNAs (miRs) by expression profiling using a PU.1-inducible myeloid progenitor cell line model. We provide evidence that PU.1 directly controls expression of at least 4 of these miRs (miR-146a, miR-342, miR338, and miR-155) through temporally dynamic occupation of binding sites within regulatory chromatin regions adjacent to their genomic coding loci. Ectopic expression of the most robustly induced PU.1 target miR, miR-146a, directed the selective differentiation of HSCs into functional peritoneal macrophages in mouse transplantation assays. In agreement with this observation, disruption of Dicer expression or specific antagonization of miR-146a function inhibited the formation of macrophages during early zebrafish (Danio rerio) development. In the present study, we describe a PU.1-orchestrated miR program that mediates key functions of PU.1 during myeloid differentiation. (Blood. 2011; 118(8): 2275-2284)

引用

页码：2275 / 2284

页数：10

共 51 条

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