MIR-23A microRNA cluster inhibits B-cell development.
MIR-23A microRNA cluster inhibits B-cell development.
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DOI：
10.1016/j.exphem.2010.04.004
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发表时间：
2010-08
影响因子：
2.6
通讯作者：
Dahl, Richard
中科院分区：
文献类型：
--
作者：
Kong, Kimi Y.;Owens, Kristin S.;Rogers, Jason H.;Mullenix, Jason;Velu, Chinavenmeni S.;Grimes, H. Leighton;Dahl, Richard
转录因子PU.1（由Sfpi 1编码）促进骨髓分化，但目前还不清楚下游基因参与。miRNAs是一类小分子RNA，其调节许多细胞途径，包括增殖、存活和分化。本研究的目的是鉴定PU.1下游调节造血发育的miRNA。用微阵列鉴定改变PU.1诱导细胞系中表达的miRNA。通过电泳迁移率变动和染色质免疫沉淀测定分析了PU.1诱导上调的miRNA簇的启动子的PU.1结合。逆转录病毒转导造血祖细胞，以评估miRNA表达对体外和体内造血发育的影响。我们鉴定了一个miRNA簇，其初级转录物受PU.1调控。pri-miRNA编码三种成熟的miRNA：miR-23 a、miR-27 a和miR-24-2。与淋巴样细胞相比，每种miRNA在髓样细胞中更丰富。当在B细胞促进条件下培养表达23 α簇miRNA的造血祖细胞时，我们观察到与对照培养物相比，B淋巴细胞生成显著减少，骨髓生成增加。在体内，与对照细胞相比，表达miR-23 a簇的造血祖细胞产生数量减少的B细胞。miR-23 a簇是PU.1的下游靶标，参与拮抗淋巴细胞命运获得。虽然已经在PU.1下游鉴定了介导单核细胞和粒细胞发育的miRNA，但23 a簇是涉及调节髓细胞与淋巴细胞发育的第一个下游miRNA靶标。
The transcription factor PU.1 (encoded by Sfpi1) promotes myeloid differentiation but it is unclear what downstream genes are involved. MiRNAs are a class of small RNAs that regulate many cellular pathways including proliferation, survival and differentiation. The objective of this study was to identify miRNAs downstream of PU.1 that regulate hematopoietic development. MiRNAs that change expression in a PU.1-inducible cell line were identified with microarrays. The promoter for a miRNA cluster upregulated by PU.1 induction was analyzed for PU.1 binding by electrophoretic mobility shift and chromatin immunoprecipitation assays. Retroviral transduction of hematopoietic progenitors was performed to evaluate the effect of miRNA expression on hematopoietic development in vitro and in vivo. We identified a miRNA cluster whose pri-transcript is regulated by PU.1. The pri-miRNA encodes three mature miRNAs: miR-23a, miR-27a, and miR-24-2. Each miRNA is more abundant in myeloid cells compared to lymphoid cells. When hematopoietic progenitors expressing the 23a cluster miRNAs were cultured in B cell promoting conditions we observed a dramatic decrease in B lymphopoiesis and an increase in myelopoiesis compared to control cultures. In vivo, hematopoietic progenitors expressing the miR-23a cluster generate reduced numbers of B cells compared to control cells. The miR-23a cluster is a downstream target of PU.1 involved in antagonizing lymphoid cell fate acquisition. Although miRNAs have been identified downstream of PU.1 in mediating the development of monocytes and granulocytes, the 23a cluster is the first downstream miRNA target implicated in regulating the development of myeloid versus lymphoid cells.
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影响因子：
56.9
作者：
Celeste, A;Petersen, S;Nussenzweig, A
通讯作者：
Nussenzweig, A
影响因子：
64.5
作者：
Laslo, Peter;Spooner, Chauncey J.;Singh, Harinder
通讯作者：
Singh, Harinder
影响因子：
16
作者：
Lal A;Navarro F;Maher CA;Maliszewski LE;Yan N;O'Day E;Chowdhury D;Dykxhoorn DM;Tsai P;Hofmann O;Becker KG;Gorospe M;Hide W;Lieberman J
通讯作者：
Lieberman J
影响因子：
11.8
作者：
Lu, Jun;Guo, Shangqin;Golub, Todd R.
通讯作者：
Golub, Todd R.
影响因子：
6.5
作者：
Feng, Jue;Iwama, Atsushi;Kohu, Kazuyoshi
通讯作者：
Kohu, Kazuyoshi