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

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Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge. / Shemer, Anat; Grozovski, Jonathan; Tay, Tuan Leng; Tao, Jenhan; Volaski, Alon; Süß, Patrick; Ardura-Fabregat, Alberto; Gross-Vered, Mor; Kim, Jung-Seok; David, Eyal; Chappell-Maor, Louise; Thielecke, Lars; Glass, Christopher K; Cornils, Kerstin; Prinz, Marco; Jung, Steffen.

In: NAT COMMUN, Vol. 9, No. 1, 06.12.2018, p. 5206.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Shemer, A, Grozovski, J, Tay, TL, Tao, J, Volaski, A, Süß, P, Ardura-Fabregat, A, Gross-Vered, M, Kim, J-S, David, E, Chappell-Maor, L, Thielecke, L, Glass, CK, Cornils, K, Prinz, M & Jung, S 2018, 'Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge', NAT COMMUN, vol. 9, no. 1, pp. 5206. https://doi.org/10.1038/s41467-018-07548-5

APA

Shemer, A., Grozovski, J., Tay, T. L., Tao, J., Volaski, A., Süß, P., Ardura-Fabregat, A., Gross-Vered, M., Kim, J-S., David, E., Chappell-Maor, L., Thielecke, L., Glass, C. K., Cornils, K., Prinz, M., & Jung, S. (2018). Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge. NAT COMMUN, 9(1), 5206. https://doi.org/10.1038/s41467-018-07548-5

Vancouver

Shemer A, Grozovski J, Tay TL, Tao J, Volaski A, Süß P et al. Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge. NAT COMMUN. 2018 Dec 6;9(1):5206. https://doi.org/10.1038/s41467-018-07548-5

Bibtex

@article{250c70a36b00463ebcdd39e4ec92a4de,
title = "Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge",
abstract = "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.",
keywords = "Animals, Brain, Cell Proliferation, Chromatin, Female, Hematopoietic Stem Cell Transplantation, Humans, Lipopolysaccharides, Macrophages, Male, Mice, Inbred C57BL, Mice, Transgenic, Microglia, Transcriptome, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",
author = "Anat Shemer and Jonathan Grozovski and Tay, {Tuan Leng} and Jenhan Tao and Alon Volaski and Patrick S{\"u}{\ss} and Alberto Ardura-Fabregat and Mor Gross-Vered and Jung-Seok Kim and Eyal David and Louise Chappell-Maor and Lars Thielecke and Glass, {Christopher K} and Kerstin Cornils and Marco Prinz and Steffen Jung",
year = "2018",
month = dec,
day = "6",
doi = "10.1038/s41467-018-07548-5",
language = "English",
volume = "9",
pages = "5206",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge

AU - Shemer, Anat

AU - Grozovski, Jonathan

AU - Tay, Tuan Leng

AU - Tao, Jenhan

AU - Volaski, Alon

AU - Süß, Patrick

AU - Ardura-Fabregat, Alberto

AU - Gross-Vered, Mor

AU - Kim, Jung-Seok

AU - David, Eyal

AU - Chappell-Maor, Louise

AU - Thielecke, Lars

AU - Glass, Christopher K

AU - Cornils, Kerstin

AU - Prinz, Marco

AU - Jung, Steffen

PY - 2018/12/6

Y1 - 2018/12/6

N2 - 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.

AB - 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.

KW - Animals

KW - Brain

KW - Cell Proliferation

KW - Chromatin

KW - Female

KW - Hematopoietic Stem Cell Transplantation

KW - Humans

KW - Lipopolysaccharides

KW - Macrophages

KW - Male

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Microglia

KW - Transcriptome

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/s41467-018-07548-5

DO - 10.1038/s41467-018-07548-5

M3 - SCORING: Journal article

C2 - 30523248

VL - 9

SP - 5206

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -