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

• Published in: Experimental hematology 2024-12, Vol.140, p.104667, Article 104667
• Main Authors: Tran, Vu L., Haltalli, Myriam L.R., Li, Jingjing, Lin, Dawn S., Yamashita, Masayuki, Naik, Shalin H., Rothenberg, Ellen V.
• Format: Article
• Language: English
• Subjects: Animals; B-Lymphocytes - cytology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Cell Differentiation; Cell Lineage; Epigenesis, Genetic; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Humans; Lymphocytes - cytology; Lymphocytes - immunology; Lymphocytes - metabolism; Lymphopoiesis - genetics; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0301-472X; 1873-2399; 1873-2399
• DOI: 10.1016/j.exphem.2024.104667

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. •MPP4 is a mixed population of myeloid and lymphoid-primed progenitors.•Earliest lymphoid priming can occur at the MPP4 stage and detected using CD69.•Notch signaling directs multipotent progenitors into the T-cell pathway while blocking alternative fates.•Early T-cell commitment involves a "tug-of-war” between HSPC-inherited and T cell-specific transcription factors.