Ever-evolving insights into the cellular and molecular drivers of lymphoid cell development.

Lymphocytes play a critical role in adaptive immunity and defense mechanisms, but the molecular mechanisms by which hematopoietic stem and progenitor cells differentiate into T and B lymphocytes are not fully established. Pioneer studies identify several transcription factors essential for lymphoid lineage determination. Yet, many questions remain unanswered about how these transcription factors interact with each other and with chromatin at different developmental stages. This interaction regulates a network of genes and proteins, promoting lymphoid lineage differentiation while suppressing other lineages. Throughout this intricate biological process, any genetic or epigenetic interruptions can derail normal differentiation trajectories, potentially leading to various human pathologic conditions. Here, we summarize recent advances in understanding lymphoid cell development, which was the focus of the Winter 2024 International Society for Experimental Hematology webinar.