An early T cell lineage commitment checkpoint dependent on the transcription factor Bcl11b.

An early T cell lineage commitment checkpoint dependent on the transcription factor Bcl11b.
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DOI:
10.1126/science.1188989
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发表时间:
2010-07-02
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Rothenberg EV
Rothenberg EV
中科院分区:
其他
文献类型:
--
作者:
Li L;Leid M;Rothenberg EV

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调节造血祖细胞对T淋巴细胞谱系承诺的调节因子的身份尚不清楚。体内T细胞谱系承诺的最后阶段涉及抑制自然杀伤细胞潜能、抑制髓系和树突状细胞潜能以及沉默最初提供T细胞受体非依赖性自我更新能力的干细胞或前体细胞调节功能的机制。锌指转录因子Bcl11b在造血细胞类型中是T细胞特异性表达的,在T谱系承诺之前首先在前体细胞中表达。我们发现,Bcl11b对于小鼠的T细胞谱系承诺是必要的,并且在承诺的关键阶段抑制自然杀伤细胞相关基因和下调一组干细胞或祖细胞基因。
The identities of the regulators that mediate commitment of hematopoietic precursors to the T lymphocyte lineage have been unknown. The last stage of T lineage commitment in vivo involves mechanisms to suppress natural killer cell potential, to suppress myeloid and dendritic cell potential, and to silence the stem cell or progenitor cell regulatory functions that initially provide T cell receptor–independent self-renewal capability. The zinc finger transcription factor Bcl11b is T cell–specific in expression among hematopoietic cell types and is first expressed in precursors immediately before T lineage commitment. We found that Bcl11b is necessary for T lineage commitment in mice and is specifically required both to repress natural killer cell–associated genes and to down-regulate a battery of stem cell or progenitor cell genes at the pivotal stage of commitment.
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