Single-cell RNA-seq Reveals a Concomitant Delay in Differentiation and Cell Cycle of Aged Hematopoietic Stem Cells

Overview

Journal BMC Biol

Publisher Biomed Central

Specialty Biology

Date 2021 Feb 2

PMID 33526011

Citations 26

Authors

Leonard Herault

Mathilde Poplineau

Adrien Mazuel

Nadine Platet

Elisabeth Remy

Estelle Duprez

Affiliations

Soon will be listed here.

Abstract

Background: Hematopoietic stem cells (HSCs) are the guarantor of the proper functioning of hematopoiesis due to their incredible diversity of potential. During aging, heterogeneity of HSCs changes, contributing to the deterioration of the immune system. In this study, we revisited mouse HSC compartment and its transcriptional plasticity during aging at unicellular scale.

Results: Through the analysis of 15,000 young and aged transcriptomes, we identified 15 groups of HSCs revealing rare and new specific HSC abilities that change with age. The implantation of new trajectories complemented with the analysis of transcription factor activities pointed consecutive states of HSC differentiation that were delayed by aging and explained the bias in differentiation of older HSCs. Moreover, reassigning cell cycle phases for each HSC clearly highlighted an imbalance of the cell cycle regulators of very immature aged HSCs that may contribute to their accumulation in an undifferentiated state.

Conclusions: Our results establish a new reference map of HSC differentiation in young and aged mice and reveal a potential mechanism that delays the differentiation of aged HSCs and could promote the emergence of age-related hematologic diseases.

Citing Articles

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