Continuous map of early hematopoietic stem cell differentiation across human lifetime

• DOI: 10.1038/s41467-025-57096-y
• Publication Date: 2025-03-07T11:47:04Z
• Authors: Hana Komic; Tessa Schmachtel; Catia Simoes; Marius Külp; Weijia Yu; Adrien Jolly; Malin S. Nilsson; Carmen Gonzalez; Felipe Prosper; Halvard Bonig; Bruno Paiva; Fredrik B. Thorén; Michael A. Rieger

Abstract Uncovering early gene network changes of human hematopoietic stem cells (HSCs) leading to differentiation induction is utmost importance for therapeutic manipulation. We employed single cell proteo-transcriptomic sequencing FACS-enriched bone marrow and progenitor (HSPCs) from 15 healthy donors. Pseudotime analysis reveals four major trajectories, which remain consistent upon aging, with an branching point into megakaryocyte-erythroid progenitors. However, young donors suggest a more productive HSPCs committed progenitors all lineages. tradeSeq depicts continuous in expression HSPC-related genes ( DLK1, ADGRG6 ), provides roadmap at the earliest points. identify CD273/PD-L2 be highly expressed subfraction immature multipotent enhanced quiescence. Functional experiments confirm immune-modulatory function on regulating T-cell activation cytokine release. Here, we present molecular map HSPC across life.