Bone marrow niches for hematopoietic stem cells in homeostasis and aging

IF 2.5 4区 医学 Q2 HEMATOLOGY
Taichi Nakatani, Takashi Nagasawa
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引用次数: 0

Abstract

Among various types of candidate cells, including osteoblasts and Nestin+ periarteriolar cells, several lines of histological and genetic evidence have demonstrated that the single population of mesenchymal stem cells, termed CXC chemokine ligand 12 (CXCL12)–abundant reticular (CAR) cells, which overlap strongly with leptin receptor–expressing (LepR+) cells, is the major cellular component of niches for hematopoietic stem cells (HSCs) and hematopoiesis in the bone marrow (BM). Expression of p16, a marker for senescent cells, and interleukin (IL)-1β and γH2AX foci, a marker for DNA damage, were increased in CAR/LepR+ cells and osteoblasts with age. However, the most striking phenotype of aging in the human BM is yellow marrow, which consists predominantly of adipocytes, causing the decreased volume of the principal site of hematopoiesis probably with the decreased numbers of HSCs in the total body. BM adipocytes are derived from CAR/LepR+ cells and act as negative or positive regulators of HSCs during homeostasis and myelosuppressive condition. Therefore, a fundamental question is how a portion of BM CAR/LepR+ cells differentiate into adipocytes during aging. Many rounds of inflammatory stress induced yellow marrow in mice. On the other hand, type H vessels found in the metaphysis and peripheral nerves running along the arteries were markedly reduced in the marrow of aged mice, which might affect HSCs and/or their niche cells. Understanding the cellular and molecular function of aged HSC niches could enable pharmacological regulation of niche functions to facilitate control of disease caused by BM aging.
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来源期刊
Experimental hematology
Experimental hematology 医学-血液学
CiteScore
5.30
自引率
0.00%
发文量
84
审稿时长
58 days
期刊介绍: Experimental Hematology publishes new findings, methodologies, reviews and perspectives in all areas of hematology and immune cell formation on a monthly basis that may include Special Issues on particular topics of current interest. The overall goal is to report new insights into how normal blood cells are produced, how their production is normally regulated, mechanisms that contribute to hematological diseases and new approaches to their treatment. Specific topics may include relevant developmental and aging processes, stem cell biology, analyses of intrinsic and extrinsic regulatory mechanisms, in vitro behavior of primary cells, clonal tracking, molecular and omics analyses, metabolism, epigenetics, bioengineering approaches, studies in model organisms, novel clinical observations, transplantation biology and new therapeutic avenues.
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