Knockdown of Pu.1 by small interfering RNA in CD34+ embryoid body cells derived from mouse ES cells turns cell fate determination to pro-B cells.
Knockdown of Pu.1 by small interfering RNA in CD34+ embryoid body cells derived from mouse ES cells turns cell fate determination to pro-B cells.
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在小鼠 ES 细胞衍生的 CD34 胚状体细胞中，通过小干扰 RNA 敲低 Pu.1，将细胞命运决定转向亲 B 细胞。
DOI：
10.1073/pnas.0506218102
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发表时间：
2005
影响因子：
11.1
通讯作者：
Rowley,JanetD
中科院分区：
文献类型：
--
作者：
Zou,Gang-Ming;Chen,Jian-Jun;Yoder,MervinC;Wu,Wei;Rowley,JanetD
The factors that regulate murine ES cell-derived hematopoietic progenitor cell (HPC) commitment to the B lymphocyte lineage remain unclear.Pu.1plays an essential role in the development of all lymphoid lineages; however, it also regulates commitment to other blood cell lineages. In this study, we found evidence for early B cell lineage commitment as determined by coexpression of CD19 and CD45R (B220) whenPu.1expression was knocked down in HPC by specific small interfering RNA (siRNA); moreover, the expression of early B cell factor (Ebf) and paired box protein 5 (Pax-5) transcription factors was induced when cells were treated byPu.1siRNA, but not by control siRNA. We also found that siRNA-mediated knockdown ofPu.1expression was more efficient in generating progenitor B cells (pro-B cells) compared with the more commonin vitromethod of B lymphoid development by means of coculture of CD34+embryoid body (EB) cells with OP9 stromal cells. To investigate whether this phenomenon also exists in HPC from other sources, we then knocked downPu.1gene expression in CD34+murine bone marrow cells and found a similar effect of increased production of CD19+CD43+CD45R+progenitor B cells upon the siRNA-mediated decrease inPu.1expression. We conclude that, in early B cell development from ES cell-derived HPC, constitutivePu.1expression inhibits the earliest B cell development through repressing early B cell factor and paired box protein 5 expression, although lower levels ofPu.1expression in HPC play a key role in promoting B cell fate determination.
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