Cutting Edge: Lymphomyeloid-Primed Progenitor Cell Fates Are Controlled by the Transcription Factor Tal1.
Renée F de PooterSheila DiasMunmun ChowdhuryElizabeth Thomas BartomMichael K OkoreehMikael SigvardssonBarbara L KeePublished in: Journal of immunology (Baltimore, Md. : 1950) (2019)
Lymphoid specification is the process by which hematopoietic stem cells (HSCs) and their progeny become restricted to differentiation through the lymphoid lineages. The basic helix-loop-helix transcription factors E2A and Lyl1 form a complex that promotes lymphoid specification. In this study, we demonstrate that Tal1, a Lyl1-related basic helix-loop-helix transcription factor that promotes T acute lymphoblastic leukemia and is required for HSC specification, erythropoiesis, and megakaryopoiesis, is a negative regulator of murine lymphoid specification. We demonstrate that Tal1 limits the expression of multiple E2A target genes in HSCs and controls the balance of myeloid versus T lymphocyte differentiation potential in lymphomyeloid-primed progenitors. Our data provide insight into the mechanisms controlling lymphocyte specification and may reveal a basis for the unique functions of Tal1 and Lyl1 in T acute lymphoblastic leukemia.
Keyphrases
- transcription factor
- dna binding
- acute lymphoblastic leukemia
- cell fate
- stem cells
- genome wide identification
- bone marrow
- allogeneic hematopoietic stem cell transplantation
- genome wide
- poor prognosis
- peripheral blood
- dna methylation
- acute myeloid leukemia
- single cell
- machine learning
- dendritic cells
- long non coding rna
- artificial intelligence
- deep learning
- cell therapy
- big data
- bioinformatics analysis