Processes regulating early lymphocyte differentiation

Lymphocytes play pivotal roles in innate and adaptive immunity. The differentiation process by which hematopoietic stem cells (HSCs) acquire specific functions has been extensively investigated and is considered the paradigm of cell differentiation. It has been widely accepted that highly enriched HSCs are heterogeneous with respect to their lymphopoietic potential, and aged or stressed HSCs are skewed to the myeloid lineage. Several transcription factors and cytokine signaling pathways have been reported as essential to lymphocyte differentiation. However, the molecular mechanism that modulates the earliest stage remains unclear. Furthermore, the origin and characteristics of early T-lymphoid progenitors that migrate from the bone marrow to the thymus are still unknown in this field. Epigenetic mechanisms likely influence early lineage specification through the regulation of mitochondrial function and modification of nuclear chromatin structure. This review summarizes previous and recent findings on the processes involved in early lymphocyte differentiation. Thus, it provides a foundation for the understanding of the physiology of HSC aging and the pathology of intractable acute lymphocytic leukemia.