TY  - JOUR
AU  - Komic, Hana
AU  - Schmachtel, Tessa
AU  - Simoes, Catia
AU  - Külp, Marius
AU  - Yu, Weijia
AU  - Jolly, Adrien Simon
AU  - Nilsson, Malin S
AU  - Gonzalez, Carmen
AU  - Prosper, Felipe
AU  - Bonig, Halvard
AU  - Paiva, Bruno
AU  - Thorén, Fredrik B
AU  - Rieger, Michael A
TI  - Continuous map of early hematopoietic stem cell differentiation across human lifetime.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-00524
SP  - 2287
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Hematopoietic Stem Cells: cytology
KW  - Hematopoietic Stem Cells: metabolism
KW  - Cell Differentiation
KW  - Adult
KW  - Middle Aged
KW  - Single-Cell Analysis: methods
KW  - Male
KW  - Female
KW  - Young Adult
KW  - Aged
KW  - Aging: physiology
KW  - Aging: genetics
KW  - T-Lymphocytes: cytology
KW  - T-Lymphocytes: metabolism
KW  - Cell Lineage: genetics
KW  - Lymphocyte Activation
KW  - Gene Expression Profiling
LB  - PUB:(DE-HGF)16
C6  - pmid:40055319
DO  - DOI:10.1038/s41467-025-57096-y
UR  - https://inrepo02.dkfz.de/record/299583
ER  -