1028 – AGING-RELATED SPATIAL REMODELING OF BONE MARROW HEMATOPOIETIC STEM CELL MICROENVIRONMENTS.

IF 2.7 4区医学 Q2 HEMATOLOGY

Experimental hematology Pub Date : 2026-10-01 Epub Date: 2026-10-23 DOI:10.1016/j.exphem.2026.105523

Konstantinos Kokkaliaris

{"title":"1028 – AGING-RELATED SPATIAL REMODELING OF BONE MARROW HEMATOPOIETIC STEM CELL MICROENVIRONMENTS.","authors":"Konstantinos Kokkaliaris","doi":"10.1016/j.exphem.2026.105523","DOIUrl":null,"url":null,"abstract":"<div><div>Aging is associated with functional decline of hematopoietic stem cells (HSCs) and their supportive bone marrow (BM) microenvironment(s). However, the cumulative effect of biological aging on BM tissue organization in situ remains poorly understood. To address this challenge, we systematically quantified multiple BM and hematopoietic populations in adult, middle-aged, and old mice using three-dimensional (3D) tissue-wide imaging cytometry. We identified spatially distinct hematopoietic microenvironments (HeMs) with distinct cellular composition and quantified their topographic remodeling during aging. We reported that HSCs associate with multiple HeMs, but those that contain most of the repopulation activity are localized in perisinusoidal diaphyseal locations enriched in megakaryocytes although being spatially segregated from all other studied BM populations. Interestingly, we demonstrated that exposure to systemic stress induced persistent BM alterations that recapitulated age-associated phenotypes. Our work provided an integrative framework linking spatial tissue organization with HSC behavior across physiological and stress states.</div></div><div>Aging is associated with functional decline of hematopoietic stem cells (HSCs) and their supportive bone marrow (BM) microenvironment(s). However, the cumulative effect of biological aging on BM tissue organization in situ remains poorly understood. To address this challenge, we systematically quantified multiple BM and hematopoietic populations in adult, middle-aged, and old mice using three-dimensional (3D) tissue-wide imaging cytometry. We identified spatially distinct hematopoietic microenvironments (HeMs) with distinct cellular composition and quantified their topographic remodeling during aging. We reported that HSCs associate with multiple HeMs, but those that contain most of the repopulation activity are localized in perisinusoidal diaphyseal locations enriched in megakaryocytes although being spatially segregated from all other studied BM populations. Interestingly, we demonstrated that exposure to systemic stress induced persistent BM alterations that recapitulated age-associated phenotypes. Our work provided an integrative framework linking spatial tissue organization with HSC behavior across physiological and stress states.</div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"162 ","pages":"Article 105523"},"PeriodicalIF":2.7000,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental hematology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0301472X26001566","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/10/23 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Aging is associated with functional decline of hematopoietic stem cells (HSCs) and their supportive bone marrow (BM) microenvironment(s). However, the cumulative effect of biological aging on BM tissue organization in situ remains poorly understood. To address this challenge, we systematically quantified multiple BM and hematopoietic populations in adult, middle-aged, and old mice using three-dimensional (3D) tissue-wide imaging cytometry. We identified spatially distinct hematopoietic microenvironments (HeMs) with distinct cellular composition and quantified their topographic remodeling during aging. We reported that HSCs associate with multiple HeMs, but those that contain most of the repopulation activity are localized in perisinusoidal diaphyseal locations enriched in megakaryocytes although being spatially segregated from all other studied BM populations. Interestingly, we demonstrated that exposure to systemic stress induced persistent BM alterations that recapitulated age-associated phenotypes. Our work provided an integrative framework linking spatial tissue organization with HSC behavior across physiological and stress states.

查看原文本刊更多论文

[28]与衰老相关的骨髓造血干细胞微环境空间重构。

衰老与造血干细胞（hsc）及其支持性骨髓（BM）微环境的功能下降有关。然而，生物老化对原位BM组织的累积效应仍然知之甚少。为了解决这一挑战，我们使用三维（3D）组织范围成像细胞术系统地量化了成年、中年和老年小鼠的多个BM和造血群体。我们确定了具有不同细胞组成的空间上不同的造血微环境（HeMs），并量化了它们在衰老过程中的地形重塑。我们报道了造血干细胞与多个造血干细胞相关，但那些包含大多数再种群活性的造血干细胞定位于富含巨核细胞的窦周骨干位置，尽管它们在空间上与所有其他研究的骨髓干细胞群体分离。有趣的是，我们证明了暴露于系统性应激诱导持续的BM改变，再现了与年龄相关的表型。我们的工作提供了一个综合框架，将空间组织组织与生理和应激状态下的HSC行为联系起来。衰老与造血干细胞（hsc）及其支持性骨髓（BM）微环境的功能下降有关。然而，生物老化对原位BM组织的累积效应仍然知之甚少。为了解决这一挑战，我们使用三维（3D）组织范围成像细胞术系统地量化了成年、中年和老年小鼠的多个BM和造血群体。我们确定了具有不同细胞组成的空间上不同的造血微环境（HeMs），并量化了它们在衰老过程中的地形重塑。我们报道了造血干细胞与多个造血干细胞相关，但那些包含大多数再种群活性的造血干细胞定位于富含巨核细胞的窦周骨干位置，尽管它们在空间上与所有其他研究的骨髓干细胞群体分离。有趣的是，我们证明了暴露于系统性应激诱导持续的BM改变，再现了与年龄相关的表型。我们的工作提供了一个综合框架，将空间组织组织与生理和应激状态下的HSC行为联系起来。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Experimental hematology 医学-血液学

CiteScore

5.30

自引率

0.00%

发文量

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.