Infiltrating lipid-rich macrophage subpopulations identified as a regulator of increasing prostate size in human benign prostatic hyperplasia

Author:

Lanman Nadia A.,Meco Era,Fitchev Philip,Kolliegbo Andree K.,Broman Meaghan M.,Filipovich Yana,Kothandaraman Harish,Cresswell Gregory M.,Talaty Pooja,Antoniak Malgorzata,Brumer Svetlana,Glaser Alexander P.,Higgins Andrew M.,Helfand Brian T.,Franco Omar E.,Crawford Susan E.,Ratliff Timothy L.,Hayward Simon W.ORCID,Vickman Renee E.ORCID

Abstract

AbstractMacrophages exhibit marked phenotypic heterogeneity within and across disease states, with lipid metabolic reprogramming contributing to macrophage activation and heterogeneity. Chronic inflammation has been observed in human benign prostatic hyperplasia (BPH) tissues, however macrophage activation states and their contributions to this hyperplastic disease have not been defined. We postulated that a shift in macrophage phenotypes with increasing prostate size could involve metabolic alterations resulting in prostatic epithelial or stromal hyperplasia. Single-cell RNA-seq of CD45+transition zone leukocytes from 10 large (>90 grams) and 10 small (<40 grams) human prostates was conducted. Macrophage subpopulations were defined using marker genes. BPH macrophages do not distinctly categorize into M1 and M2 phenotypes. Instead, macrophages with neither polarization signature preferentially accumulate in large versus small prostates. Specifically, macrophage subpopulations with altered lipid metabolism pathways, demarcated byTREM2andMARCOexpression, significantly accumulate with increased prostate volume.TREM2+andMARCO+macrophage abundance positively correlates with patient body mass index and urinary symptom scores. TREM2+macrophages have significantly higher neutral lipid than TREM2macrophages from BPH tissues. Lipid-rich macrophages were observed to localize within the stroma in BPH tissues.In vitrostudies indicate that lipid-loaded macrophages increase prostate epithelial and stromal cell proliferation compared to control macrophages. These data define two new BPH immune subpopulations, TREM2+and MARCO+macrophages, and suggest that lipid-rich macrophages may exacerbate lower urinary tract symptoms in patients with large prostates. Further investigation is needed to evaluate the therapeutic benefit of targeting these cells in BPH.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3