| RRC ID |
68061
|
| Author |
Hirano KI, Hosokawa H, Koizumi M, Endo Y, Yahata T, Ando K, Hozumi K.
|
| Title |
LMO2 is essential to maintain the ability of progenitors to differentiate into T-cell lineage in mice.
|
| Journal |
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.
|
| Volume |
10
|
| Published |
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
|
| Resource |
| DNA material |
pCAG-HIVgp (RDB04394)
pCMV-VSV-G-RSV-Rev (RDB04393) |
