Single-cell RNA-seq reveals a concomitant delay in differentiation and cell cycle of aged hematopoietic stem cell

Abstract

Hematopoietic stem cells (HSCs) are the guarantor of the proper functioning of hematopoiesis due to their incredible diversity of potential. During aging the heterogeneity of mouse HSCs evolves, which contributes to the deterioration of the immune system. Here we address the transcriptional plasticity of HSC upon aging at the single-cell resolution. Through the analysis of 15,000 young and aged transcriptomes, we reveal 15 clusters of HSCs unveiling rare and specific HSC abilities that change with age. Pseudotime ordering complemented with regulon analysis showed that the consecutive differentiation states of HSC are delayed upon aging. By analysing cell cycle at the single cell level we highlight an imbalance of cell cycle regulators of very immature aged HSC that may contribute to their accumulation in an undifferentiated state. Our results therefore establish a reference map of young and old mouse HSC differentiation and reveal a potential mechanism that delay aged HSC differentiation.