Uncovering the regulatory landscape of early human B cell lymphopoiesis and its implications in the pathogenesis of B-ALL.
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Planell N, Martínez-de-Morentin X, Mouzo D, Lara-Astiaso D, Vilas-Zornoza A, Martín-Uriz PS, Alignani D, Paiva B, Maillo A, Kurowska A, Berastegui N, Garcia-Olloqui P, Urdangarin A, Noori P, Ortega-Legarreta A, Hernaez M, Lagani V, Kiani N, Merkenschlager M, Ezponda T, Martín-Subero JI, Ramírez RN, Tegner J, Prosper F, Gomez-Cabrero D
Sci Adv 11 (41) eadw3110 [2025-10-10; online 2025-10-10]
Dysregulation of early B cell lymphopoiesis-the process guiding cellular immunity development-can lead to malignancy, making it crucial to understand its regulatory mechanisms. We generated a multiomics resource comprising paired chromatin accessibility and gene expression profiles across eight human B cell precursor populations, providing a detailed characterization of early human B cell development. Integrative analysis revealed highly cell type-specific regulatory elements and enabled the reconstruction of the gene regulatory network governing differentiation. We identified putative candidate regulons, such as ELK3, enriched in pro-B cells and potentially involved in cell cycle progression. Regulons from bulk data were projected onto single-cell data, validating their activity and refining the regulatory landscape. This resource enabled identification of active regulatory programs and transformation-associated states in B cell acute lymphoblastic leukemia. The publicly available atlas provides a valuable resource for understanding B cell development and disease, supporting future efforts to decode regulatory programs in immunity and hematologic malignancies.
PubMed 41071881
DOI 10.1126/sciadv.adw3110
Crossref 10.1126/sciadv.adw3110