Abstract
Hematopoietic multipotent progenitors seed the thymus and then follow consecutive developmental stages until the formation of mature T cells. During this process, phenotypic changes of T cells entail stage-specific transcriptional programs that underlie the dynamic progression towards mature lymphocytes. Lineage-specific transcription factors are key drivers of T cell specification and act in conjunction with epigenetic regulators that have also been elucidated as crucial players in the establishment of regulatory networks necessary for proper T cell development. In this review, we summarize the activity of transcription factors and epigenetic regulators that together orchestrate the intricacies of early T cell development with a focus on regulation of T cell lineage commitment.
Highlights
Hematopoiesis, the formation of blood cells, is a well-studied developmental process, during which transcription factors and epigenetic regulators operate together in order to ensure faithful progression toward the production of mature blood cells [1,2]
While most blood cell types develop in the bone marrow [7], specialized white blood cells differentiate in the thymus from multipotent progenitors that pass through different stages until they develop into mature T cells [8,9]
It is not surprising that deletion of fairly ubiquitous epigenetic mediators (HDACs, switch/sucrose non-fermentable (SWI/SNF) factors, etc.) in specific stages of T cell development leads to profound functional defects
Summary
Hematopoiesis, the formation of blood cells, is a well-studied developmental process, during which transcription factors and epigenetic regulators operate together in order to ensure faithful progression toward the production of mature blood cells [1,2]. Lineage restriction events reflect changes in the transcriptional programs and epigenetic regulation [3,4], and defects in these regulatory mechanisms can promote leukemogenesis [5,6]. These intrinsic programs require cell-extrinsic factors, such as signaling pathways, cytokines and growth factors, provided by a specific microenvironment. We discuss the journey of early thymic progenitors toward committed T cells and the lessons learned from murine models about the crucial roles of key transcription factors and epigenetic regulators in the establishment of T cell identity
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