Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic suppression of the B-lineage program.
Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic suppression of the B-lineage program.
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DOI：
10.1101/gad.290593.116
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发表时间：
2016-11-15
影响因子：
10.5
通讯作者：
Kawamoto H
中科院分区：
文献类型：
--
作者：
Ikawa T;Masuda K;Endo TA;Endo M;Isono K;Koseki Y;Nakagawa R;Kometani K;Takano J;Agata Y;Katsura Y;Kurosaki T;Vidal M;Koseki H;Kawamoto H
Ikawa等人报道，polycomb介导的表观遗传调节的失活导致T谱系祖细胞向B细胞命运的转化。这种抑制几乎完全被Pax 5的额外删除所取消。一般来说，细胞命运主要由转录因子决定，然后是固定状态的表观遗传机制。虽然转录因子控制细胞命运的重要性已得到很好的表征，细胞命运维持的表观遗传调控仍有待阐明。在这里，我们提供了一个明显的命运转换的情况下，其中多梳介导的表观遗传调控的失活的T-谱系祖细胞的B-细胞命运的转换的结果。在T细胞特异性Ring 1A/B缺陷小鼠中，T细胞发育在未成熟阶段严重受阻。我们发现这些发育停滞的T细胞前体在转移到免疫缺陷小鼠后产生功能性B细胞。我们进一步证明，通过额外删除Pax 5，几乎完全取消了逮捕。这些结果表明，T细胞命运的维持关键需要B系基因程序的表观遗传抑制。
Ikawa et al. report that the inactivation of polycomb-mediated epigenetic regulation results in the conversion of T-lineage progenitors to the B-cell fate. This arrest was almost completely cancelled by additional deletion of Pax5. In general, cell fate is determined primarily by transcription factors, followed by epigenetic mechanisms fixing the status. While the importance of transcription factors controlling cell fate has been well characterized, epigenetic regulation of cell fate maintenance remains to be elucidated. Here we provide an obvious fate conversion case, in which the inactivation of polycomb-medicated epigenetic regulation results in conversion of T-lineage progenitors to the B-cell fate. In T-cell-specific Ring1A/B-deficient mice, T-cell development was severely blocked at an immature stage. We found that these developmentally arrested T-cell precursors gave rise to functional B cells upon transfer to immunodeficient mice. We further demonstrated that the arrest was almost completely canceled by additional deletion of Pax5. These results indicate that the maintenance of T-cell fate critically requires epigenetic suppression of the B-lineage gene program.
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DOI：
10.1084/jem.20102665
发表时间：
2011-07-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kometani K;Yamada T;Sasaki Y;Yokosuka T;Saito T;Rajewsky K;Ishiai M;Hikida M;Kurosaki T
通讯作者：
Kurosaki T
DOI：
10.1126/science.1188063
发表时间：
2010-07-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li P;Burke S;Wang J;Chen X;Ortiz M;Lee SC;Lu D;Campos L;Goulding D;Ng BL;Dougan G;Huntly B;Gottgens B;Jenkins NA;Copeland NG;Colucci F;Liu P
通讯作者：
Liu P
影响因子：
32.4
作者：
Laiosa, Catherine V.;Stadtfeld, Matthias;Graf, Thomas
通讯作者：
Graf, Thomas
影响因子：
30.5
作者：
Nechanitzky, Robert;Akbas, Duygu;Grosschedl, Rudolf
通讯作者：
Grosschedl, Rudolf
影响因子：
32.4
作者：
Ikawa, T;Kawamoto, H;Murre, C
通讯作者：
Murre, C