論文 - 詳細
| RRC ID | 68061 |
|---|---|
| 著者 | Hirano KI, Hosokawa H, Koizumi M, Endo Y, Yahata T, Ando K, Hozumi K. |
| タイトル | LMO2 is essential to maintain the ability of progenitors to differentiate into T-cell lineage in mice. |
| ジャーナル | Elife |
| Abstract |
Notch signaling primarily determines T-cell fate. However, the molecular mechanisms underlying the maintenance of T-lineage potential in pre-thymic progenitors remain unclear. Here, we established two murine Ebf1-deficient pro-B cell lines, with and without T-lineage potential. The latter expressed lower levels of Lmo2; their potential was restored via ectopic expression of Lmo2. Conversely, the CRISPR/Cas9-mediated deletion of Lmo2 resulted in the loss of the T-lineage potential. Introduction of Bcl2 rescued massive cell death of Notch-stimulated pro-B cells without efficient LMO2-driven Bcl11a expression but was not sufficient to retain their T-lineage potential. Pro-B cells without T-lineage potential failed to activate Tcf7 due to DNA methylation; Tcf7 transduction restored this capacity. Moreover, direct binding of LMO2 to the Bcl11a and Tcf7 loci was observed. Altogether, our results highlight LMO2 as a crucial player in the survival and maintenance of T-lineage potential in T-cell progenitors via the regulation of the expression of Bcl11a and Tcf7. |
| 巻・号 | 10 |
| 公開日 | 2021-8-12 |
| DOI | 10.7554/eLife.68227 |
| PII | 68227 |
| PMID | 34382935 |
| PMC | PMC8360648 |
| MeSH | Adaptor Proteins, Signal Transducing / genetics* Adaptor Proteins, Signal Transducing / metabolism Animals Cell Differentiation / genetics* Cell Lineage / genetics* Female LIM Domain Proteins / genetics* LIM Domain Proteins / metabolism Male Mice T-Lymphocytes / physiology* |
| IF | 7.08 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |