Microenvironmental contributions to hematopoietic stem cell aging.


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Authors
Ho, Ya-Hsuan 
Méndez-Ferrer, Simón  ORCID logo  https://orcid.org/0000-0002-9805-9988
Abstract

Hematopoietic stem cell (HSC) aging was originally thought to be essentially an HSC-autonomous process, which is the focus of another review in the same issue of Haematologica However, studies on the microenvironment that maintains and regulates HSC (HSC niche) over the past 20 years have suggested that microenvironmental aging contributes to declined HSC function over time. The HSC niches comprise a complex and dynamic molecular network of interactions across multiple cell types, including endothelial cells, mesenchymal stromal cells, osteoblasts, adipocytes, neuroglial cells and mature hematopoietic cells. Upon aging, functional changes in the HSC niches, such as microenvironmental senescence, imbalanced bone marrow mesenchymal stromal cell differentiation, vascular remodeling, changes in adrenergic signaling and inflammation, coordinately and dynamically influence the fate of HSC and their downstream progeny. The end result is lymphoid deficiency and myeloid skewing. During this process, aged HSC and their derivatives remodel the niche to favor myeloid expansion. Therefore, the crosstalk between HSC and the microenvironment is indispensable for the aging of the hematopoietic system and might represent a therapeutic target in age-related pathological disorders.

Description
Keywords
Cell Differentiation, Endothelial Cells, Hematopoietic Stem Cells, Stem Cell Niche
Journal Title
Haematologica
Conference Name
Journal ISSN
0390-6078
1592-8721
Volume Title
105
Publisher
Ferrata Storti Foundation (Haematologica)
Rights
All rights reserved
Sponsorship
European Research Council (648765)
NHS Blood and Transplant (NHSBT)
Cancer Research UK (C61367/A26670)
Cancer Research UK (A27831)
Medical Research Council (MC_PC_12009)
MRC (MR/V005421/1)