T cell development from expanded hematopoietic progenitors reveals initiation control by Lmo2 and Flt3L priming - PubMed
5 hours ago
- #Lmo2
- #T cell development
- #Hematopoietic progenitors
- Study adapted a serum-free expansion system for hematopoietic stem and progenitor-like cells to access early murine T cell development stages.
- Expanded cells showed normal T cell differentiation in vivo and in vitro, confirmed by single-cell RNA sequencing.
- Flt3L priming modulates the differentiation speed of these cells, which is slower than fresh progenitors.
- Earliest T cell lineage-initiating events in response to Notch signaling included chromatin opening and transcriptional activation of the TCR-Cβ locus.
- CRISPR knockouts identified transcription factors inherited from bone marrow progenitors that impede early T cell development, affecting proliferation differently.
- Lmo2 knockout accelerated onset of germline TCR-Cβ locus transcription and expression of Tcf7, Gata3, Runx1 and their targets.
- Endogenous expression of Lmo2, a progenitor- and leukemia-associated factor, restrains T cell program initiation.