The paper details a comprehensive study employing a unified multimodal single-cell framework to redefine hematopoiesis, the process of blood cell formation, in mice. Researchers integrated transcriptional (RNA), surface protein (CITE-seq, InfinityFlow), and chromatin accessibility (TEA-seq) data to identify and characterize discrete hematopoietic progenitor cell states, particularly the rare Multilineage (MultiLin) cells. This approach, using the ChromLinker computational framework, revealed hierarchical gene regulatory networks (GRNs) driving cell fate decisions and allowed for the isolation and functional validation of these novel progenitor states, which challenge previous models of continuous lineage commitment by supporting a discrete state model. The study successfully used surface proteins like CD55 and CD371 as markers to isolate and trace the distinct developmental potentials of MultiLin subsets, which respond dynamically to perturbations like infection.

References:

• Ferchen K, Zhang X, Thakkar K, et al. A unified multimodal single-cell framework reveals a discrete state model of hematopoiesis in mice[J]. Nature Immunology, 2025: 1-14.