T cell development requires constraint of the myeloid regulator C/EBP-α by the Notch target and transcriptional repressor Hes1.
T cell development requires constraint of the myeloid regulator C/EBP-α by the Notch target and transcriptional repressor Hes1.
复制标题
DOI：
10.1038/ni.2760
复制
发表时间：
2013-12
影响因子：
30.5
通讯作者：
Bhandoola, Avinash
中科院分区：
文献类型：
--
作者：
De Obaldia, Maria Elena;Bell, J. Jeremiah;Wang, Xinxin;Harly, Christelle;Yashiro-Ohtani, Yumi;DeLong, Jonathan H.;Zlotoff, Daniel A.;Sultana, Dil Afroz;Pear, Warren S.;Bhandoola, Avinash
Notch signaling induces gene expression of the T cell lineage and discourages alternative fate outcomes. Hematopoietic deficiency in the Notch target Hes1 results in severe T cell lineage defects; however, the underlying mechanism is unknown. We found here that Hes1 constrained myeloid gene-expression programs in T cell progenitor cells, as deletion of the myeloid regulator C/EBPa restored the development of T cells from Hes1-deficient progenitor cells. Repression of Cebpa by Hes1 required its DNA-binding and Groucho-recruitment domains. Hes1-deficient multipotent progenitor cells showed a developmental bias toward myeloid and dendritic cells after Notch signaling, whereas Hes1-deficient lymphoid progenitor cells required additional cytokine signaling for diversion into the myeloid lineage. Our findings establish the importance of constraining developmental programs of the myeloid lineage early in T cell development.
登录
查看更多内容
影响因子：
--
作者：
Ross, DA;Hannenhalli, S;Kadesch, T
通讯作者：
Kadesch, T
影响因子：
20.3
作者：
Mansson, Robert;Zandi, Sasan;Sigvardsson, Mikael
通讯作者：
Sigvardsson, Mikael
影响因子：
64.8
作者：
ARDAVIN, C;WU, L;SHORTMAN, K
通讯作者：
SHORTMAN, K
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：
32.4
作者：
Igarashi, H;Gregory, SC;Kincade, PW
通讯作者：
Kincade, PW