TCEA1 regulates the proliferative potential of mouse myeloid cells.
TCEA1 regulates the proliferative potential of mouse myeloid cells.
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TCEA1 调节小鼠骨髓细胞的增殖潜力
DOI：
10.1016/j.yexcr.2018.07.020
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发表时间：
2018-09-15
影响因子：
3.7
通讯作者：
Wei G
中科院分区：
文献类型：
--
作者：
Yang T;Cui H;Wen M;Zuber J;Kogan SC;Wei G
白血病是一种发病机制复杂、预后差的恶性肿瘤。发现新的白血病调节因子对了解白血病的发病机制、诊断和预后具有重要价值。在这里，我们进行了一个大规模的shRNA文库筛选的功能调节剂在原代细胞中的骨髓细胞的发展。我们在初步筛选中确定了18个候选监管机构。这些基因具有广泛的细胞功能，包括基因表达调控、细胞内信号转导、核苷酸切除修复、细胞周期调控和转录调控。在初步筛选和验证中，靶向编码转录延伸因子A（SII）1的Tcea 1的shRNA对细胞增殖潜力的影响最大。敲低Tcea 1在32 Dcl 3髓系细胞系中的表达导致髓系细胞的增殖增强和G-CSF诱导的髓系分化的阻断。此外，沉默Tcea 1抑制髓系细胞的凋亡。因此，Tcea 1被鉴定为可以影响骨髓细胞的增殖潜能、存活和分化的基因。这些发现对转录延长如何影响髓系细胞发育和白血病转化具有重要意义。
Leukemia is a malignance with complex pathogenesis and poor prognosis. Discovery of new regulators is amenable to leukemia could be of value to gain insight into the pathogenesis, diagnosis and prognosis of leukemia. Here, we conducted a large-scale shRNA library screening for functional regulators in the development of myeloid cells in primary cells. We identified eighteen candidate regulators in the primary screening. Those genes cover a wide range of cellular functions, including gene expression regulation, intracellular signaling transduction, nucleotide excision repair, cell cycle control and transcription regulation. In both primary screening and validation, shRNAs targeting Tcea1, encoding the transcription elongation factor A (SII) 1, exhibited the greatest influence on the proliferative potential of cells. Knocking down the expression of Tcea1 in the 32Dcl3 myeloid cell line led to enhanced proliferation of myeloid cells and blockage of G-CSF induced myeloid differentiation. In addition, silencing of Tcea1 inhibited apoptosis of myeloid cells. Thus, Tcea1, was identified as a gene which can influence the proliferative potential, survival and differentiation of myeloid cells. These findings have implications for how transcriptional elongation influences myeloid cell development and leukemic transformation.
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影响因子：
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