2025-03-21 ゲーテ大学
<関連情報>
- https://aktuelles.uni-frankfurt.de/english/nursery-of-the-blood-how-stem-cells-calm-the-bodys-immune-response/
- https://www.nature.com/articles/s41467-025-57096-y
ヒトの生涯にわたる初期造血幹細胞分化の連続マップ Continuous map of early hematopoietic stem cell differentiation across human lifetime
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
Nature Communications Published:07 March 2025
DOI:https://doi.org/10.1038/s41467-025-57096-y
Abstract
Uncovering early gene network changes of human hematopoietic stem cells (HSCs) leading to differentiation induction is of utmost importance for therapeutic manipulation. We employed single cell proteo-transcriptomic sequencing to FACS-enriched bone marrow hematopoietic stem and progenitor cells (HSPCs) from 15 healthy donors. Pseudotime analysis reveals four major differentiation trajectories, which remain consistent upon aging, with an early branching point into megakaryocyte-erythroid progenitors. However, young donors suggest a more productive differentiation from HSPCs to committed progenitors of all lineages. tradeSeq analysis depicts continuous changes in gene expression of HSPC-related genes (DLK1, ADGRG6), and provides a roadmap of gene expression at the earliest branching points. We identify CD273/PD-L2 to be highly expressed in a subfraction of immature multipotent HSPCs with enhanced quiescence. Functional experiments confirm the immune-modulatory function of CD273/PD-L2 on HSPCs in regulating T-cell activation and cytokine release. Here, we present a molecular map of early HSPC differentiation across human life.
