Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge

被引：176

作者：

Shemer, Anat ^{[1
]}

Grozoyski, Jonathan ^{[1
]}

Tay, Tuan Leng ^{[2
,3
,4
]}

Tao, Jenhan ^{[5
]}

Volaski, Alon ^{[1
]}

Suess, Patrick ^{[3
]}

Ardura-Fabregat, Alberto ^{[3
]}

Gross-Vered, Mor ^{[1
]}

Kim, Jung-Seok ^{[1
]}

David, Eyal ^{[1
]}

Chappell-Maor, Louise ^{[1
]}

Thielecke, Lars ^{[6
]}

Glass, Christopher K. ^{[5
]}

Cornils, Kerstin ^{[7
,8
]}

Prinz, Marco ^{[3
,9
,10
]}

Jung, Steffen ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel

[2] Univ Freiburg, Cluster Excellence BrainLinks BrainTools, D-79110 Freiburg, Germany

[3] Univ Freiburg, Med Fac, Inst Neuropathol, D-79106 Freiburg, Germany

[4] Univ Freiburg, Fac Biol, Inst Biol Zool 1, D-79104 Freiburg, Germany

[5] Univ Calif San Diego, Dept Cellular & Mol Med, 9500 Gilman Dr, La Jolla, CA 92093 USA

[6] Tech Univ Dresden, Fac Med Carl Gustav Carus, Inst Med Informat & Biometry, Dresden, Germany

[7] Univ Med Ctr Hamburg Eppendorf, Dept Pediat Hematol & Oncol, Div Pediat Stem Cell Transplantat & Immunol, D-20246 Hamburg, Germany

[8] Childrens Canc Ctr Hamburg, Res Inst, D-20246 Hamburg, Germany

[9] Univ Freiburg, BIOSS Ctr Biol Signalling Studies, D-79104 Freiburg, Germany

[10] Univ Freiburg, CIBSS, D-79104 Freiburg, Germany

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

欧洲研究理事会;

关键词：

CENTRAL-NERVOUS-SYSTEM; RESIDENT MICROGLIA; P2Y(12) RECEPTOR; MONOCYTES; REVEALS; FATE; DYNAMICS; ORIGIN; NICHE; CELLS;

D O I：

10.1038/s41467-018-07548-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Microglia are yolk sac-derived macrophages residing in the parenchyma of brain and spinal cord, where they interact with neurons and other glial. After different conditioning paradigms and bone marrow (BM) or hematopoietic stem cell (HSC) transplantation, graft-derived cells seed the brain and persistently contribute to the parenchymal brain macrophage compartment. Here we establish that graft-derived macrophages acquire, over time, microglia characteristics, including ramified morphology, longevity, radio-resistance and clonal expansion. However, even after prolonged CNS residence, transcriptomes and chromatin accessibility landscapes of engrafted, BM-derived macrophages remain distinct from yolk sac-derived host microglia. Furthermore, engrafted BM-derived cells display discrete responses to peripheral endotoxin challenge, as compared to host microglia. In human HSC transplant recipients, engrafted cells also remain distinct from host microglia, extending our finding to clinical settings. Collectively, our data emphasize the molecular and functional heterogeneity of parenchymal brain macrophages and highlight potential clinical implications for HSC gene therapies aimed to ameliorate lysosomal storage disorders, microgliopathies or general monogenic immuno-deficiencies.

引用

页数：16

共 72 条

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