Scientific publications
Uncovering the regulatory landscape of early human B cell lymphopoiesis and its implications in the pathogenesis of B-ALL
Núria Planell 1 2, Xabier Martínez-de-Morentin 2 3, Daniel Mouzo 2, David Lara-Astiaso 4, Amaia Vilas-Zornoza 4, Patxi San Martín-Uriz 4, Diego Alignani 5, Bruno Paiva 6, Alberto Maillo 3, Aleksandra Kurowska 3, Nerea Berastegui 4, Paula Garcia-Olloqui 4, Arantxa Urdangarin 2, Peri Noori 7, Asier Ortega-Legarreta 2, Mikel Hernaez 1, Vincenzo Lagani 3 8 9, Narsis Kiani 10 11, Matthias Merkenschlager 12, Teresa Ezponda 4, José I Martín-Subero 13 14, Ricardo N Ramírez 15, Jesper Tegner 16 17 18 19, Felipe Prosper 4 20, David Gomez-Cabrero 2 3
Abstract
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.
CITA DEL ARTÍCULO Sci Adv. 2025 Oct 10;11(41):eadw3110. doi: 10.1126/sciadv.adw3110. Epub 2025 Oct 10.
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