miRNAs Are Essential for the Regulation of the PI3K/AKT/FOXO Pathway and Receptor Editing during B Cell Maturation.
miRNAs Are Essential for the Regulation of the PI3K/AKT/FOXO Pathway and Receptor Editing during B Cell Maturation.
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DOI：
10.1016/j.celrep.2016.11.006
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发表时间：
2016-11-22
期刊：
影响因子：
8.8
通讯作者：
Koralov SB
中科院分区：
文献类型：
--
作者：
Coffre M;Benhamou D;Rieß D;Blumenberg L;Snetkova V;Hines MJ;Chakraborty T;Bajwa S;Jensen K;Chong MMW;Getu L;Silverman GJ;Blelloch R;Littman DR;Calado D;Melamed D;Skok JA;Rajewsky K;Koralov SB
B细胞发育是一个严格调控的过程，依赖于编码抗原受体的免疫球蛋白基因座的顺序重排。为了阐明微小RNA（miRNAs）在B细胞发育的协调中的作用，我们在B细胞发育的最早阶段通过有条件地靶向早期B细胞前体中对RNAi至关重要的酶来消除所有miRNAs。这些酶中的任何一种的缺失导致由于凋亡增加和前B细胞增殖失败而导致前B细胞向前B细胞转变的阻断。Bcl 2转基因的表达允许部分拯救B细胞发育，然而，大多数拯救的B细胞具有低表面免疫球蛋白表达，有证据表明正在进行轻链编辑。我们的分析表明，miRNA对调节PTEN-AKT-FOXO 1通路至关重要，PTEN-AKT-FOXO 1通路反过来控制B细胞发育过程中的Rag表达。
B cell development is a tightly regulated process dependent on sequential rearrangements of immunoglobulin loci that encode the antigen receptor. To elucidate the role of microRNAs (miRNAs) in the orchestration of B cell development, we ablated all miRNAs at the earliest stage of B cell development by conditionally targeting the enzymes critical for RNAi in early B cell precursors. Absence of any one of these enzymes led to a block at the pro- to pre-B cell transition due to increased apoptosis and a failure of pre-B cells to proliferate. Expression of a Bcl2 transgene allowed for partial rescue of B cell development, however, the majority of the rescued B cells had low surface immunoglobulin expression with evidence of ongoing light chain editing. Our analysis revealed that miRNAs are critical for the regulation of the PTEN-AKT-FOXO1 pathway that in turn controls Rag expression during B cell development.
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影响因子：
30.5
作者：
通讯作者：
--
影响因子：
30.5
作者：
Gonzalez-Martin A;Adams BD;Lai M;Shepherd J;Salvador-Bernaldez M;Salvador JM;Lu J;Nemazee D;Xiao C
通讯作者：
Xiao C
DOI：
10.1038/nrg3355
发表时间：
2013-02
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
10.5
作者：
Babiarz, Joshua E.;Ruby, J. Graham;Blelloch, Robert
通讯作者：
Blelloch, Robert
影响因子：
64.5
作者：
EARLY, P;ROGERS, J;HOOD, L
通讯作者：
HOOD, L