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Neural metabolic imbalance induced by MOF dysfunction triggers pericyte activation and breakdown of vasculature

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Neural metabolic imbalance induced by MOF dysfunction triggers pericyte activation and breakdown of vasculature. / Sheikh, Bilal N; Guhathakurta, Sukanya; Tsang, Tsz Hong; Schwabenland, Marius; Renschler, Gina; Herquel, Benjamin; Bhardwaj, Vivek; Holz, Herbert; Stehle, Thomas; Bondareva, Olga; Aizarani, Nadim; Mossad, Omar; Kretz, Oliver; Reichardt, Wilfried; Chatterjee, Aindrila; Braun, Laura J; Thevenon, Julien; Sartelet, Herve; Blank, Thomas; Grün, Dominic; von Elverfeldt, Dominik; Huber, Tobias B; Vestweber, Dietmar; Avilov, Sergiy; Prinz, Marco; Buescher, Joerg M; Akhtar, Asifa.

In: NAT CELL BIOL, Vol. 22, No. 7, 07.2020, p. 828-841.

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

Harvard

Sheikh, BN, Guhathakurta, S, Tsang, TH, Schwabenland, M, Renschler, G, Herquel, B, Bhardwaj, V, Holz, H, Stehle, T, Bondareva, O, Aizarani, N, Mossad, O, Kretz, O, Reichardt, W, Chatterjee, A, Braun, LJ, Thevenon, J, Sartelet, H, Blank, T, Grün, D, von Elverfeldt, D, Huber, TB, Vestweber, D, Avilov, S, Prinz, M, Buescher, JM & Akhtar, A 2020, 'Neural metabolic imbalance induced by MOF dysfunction triggers pericyte activation and breakdown of vasculature', NAT CELL BIOL, vol. 22, no. 7, pp. 828-841. https://doi.org/10.1038/s41556-020-0526-8

APA

Sheikh, B. N., Guhathakurta, S., Tsang, T. H., Schwabenland, M., Renschler, G., Herquel, B., Bhardwaj, V., Holz, H., Stehle, T., Bondareva, O., Aizarani, N., Mossad, O., Kretz, O., Reichardt, W., Chatterjee, A., Braun, L. J., Thevenon, J., Sartelet, H., Blank, T., ... Akhtar, A. (2020). Neural metabolic imbalance induced by MOF dysfunction triggers pericyte activation and breakdown of vasculature. NAT CELL BIOL, 22(7), 828-841. https://doi.org/10.1038/s41556-020-0526-8

Vancouver

Sheikh BN, Guhathakurta S, Tsang TH, Schwabenland M, Renschler G, Herquel B et al. Neural metabolic imbalance induced by MOF dysfunction triggers pericyte activation and breakdown of vasculature. NAT CELL BIOL. 2020 Jul;22(7):828-841. https://doi.org/10.1038/s41556-020-0526-8

Bibtex

@article{db36d916f3d24baab2770c298f1b3d6d,
title = "Neural metabolic imbalance induced by MOF dysfunction triggers pericyte activation and breakdown of vasculature",
abstract = "Mutations in chromatin-modifying complexes and metabolic enzymes commonly underlie complex human developmental syndromes affecting multiple organs. A major challenge is to determine how disease-causing genetic lesions cause deregulation of homeostasis in unique cell types. Here we show that neural-specific depletion of three members of the non-specific lethal (NSL) chromatin complex-Mof, Kansl2 or Kansl3-unexpectedly leads to severe vascular defects and brain haemorrhaging. Deregulation of the epigenetic landscape induced by the loss of the NSL complex in neural cells causes widespread metabolic defects, including an accumulation of free long-chain fatty acids (LCFAs). Free LCFAs induce a Toll-like receptor 4 (TLR4)-NFκB-dependent pro-inflammatory signalling cascade in neighbouring vascular pericytes that is rescued by TLR4 inhibition. Pericytes display functional changes in response to LCFA-induced activation that result in vascular breakdown. Our work establishes that neurovascular function is determined by the neural metabolic environment.",
author = "Sheikh, {Bilal N} and Sukanya Guhathakurta and Tsang, {Tsz Hong} and Marius Schwabenland and Gina Renschler and Benjamin Herquel and Vivek Bhardwaj and Herbert Holz and Thomas Stehle and Olga Bondareva and Nadim Aizarani and Omar Mossad and Oliver Kretz and Wilfried Reichardt and Aindrila Chatterjee and Braun, {Laura J} and Julien Thevenon and Herve Sartelet and Thomas Blank and Dominic Gr{\"u}n and {von Elverfeldt}, Dominik and Huber, {Tobias B} and Dietmar Vestweber and Sergiy Avilov and Marco Prinz and Buescher, {Joerg M} and Asifa Akhtar",
year = "2020",
month = jul,
doi = "10.1038/s41556-020-0526-8",
language = "English",
volume = "22",
pages = "828--841",
journal = "NAT CELL BIOL",
issn = "1465-7392",
publisher = "NATURE PUBLISHING GROUP",
number = "7",

}

RIS

TY - JOUR

T1 - Neural metabolic imbalance induced by MOF dysfunction triggers pericyte activation and breakdown of vasculature

AU - Sheikh, Bilal N

AU - Guhathakurta, Sukanya

AU - Tsang, Tsz Hong

AU - Schwabenland, Marius

AU - Renschler, Gina

AU - Herquel, Benjamin

AU - Bhardwaj, Vivek

AU - Holz, Herbert

AU - Stehle, Thomas

AU - Bondareva, Olga

AU - Aizarani, Nadim

AU - Mossad, Omar

AU - Kretz, Oliver

AU - Reichardt, Wilfried

AU - Chatterjee, Aindrila

AU - Braun, Laura J

AU - Thevenon, Julien

AU - Sartelet, Herve

AU - Blank, Thomas

AU - Grün, Dominic

AU - von Elverfeldt, Dominik

AU - Huber, Tobias B

AU - Vestweber, Dietmar

AU - Avilov, Sergiy

AU - Prinz, Marco

AU - Buescher, Joerg M

AU - Akhtar, Asifa

PY - 2020/7

Y1 - 2020/7

N2 - Mutations in chromatin-modifying complexes and metabolic enzymes commonly underlie complex human developmental syndromes affecting multiple organs. A major challenge is to determine how disease-causing genetic lesions cause deregulation of homeostasis in unique cell types. Here we show that neural-specific depletion of three members of the non-specific lethal (NSL) chromatin complex-Mof, Kansl2 or Kansl3-unexpectedly leads to severe vascular defects and brain haemorrhaging. Deregulation of the epigenetic landscape induced by the loss of the NSL complex in neural cells causes widespread metabolic defects, including an accumulation of free long-chain fatty acids (LCFAs). Free LCFAs induce a Toll-like receptor 4 (TLR4)-NFκB-dependent pro-inflammatory signalling cascade in neighbouring vascular pericytes that is rescued by TLR4 inhibition. Pericytes display functional changes in response to LCFA-induced activation that result in vascular breakdown. Our work establishes that neurovascular function is determined by the neural metabolic environment.

AB - Mutations in chromatin-modifying complexes and metabolic enzymes commonly underlie complex human developmental syndromes affecting multiple organs. A major challenge is to determine how disease-causing genetic lesions cause deregulation of homeostasis in unique cell types. Here we show that neural-specific depletion of three members of the non-specific lethal (NSL) chromatin complex-Mof, Kansl2 or Kansl3-unexpectedly leads to severe vascular defects and brain haemorrhaging. Deregulation of the epigenetic landscape induced by the loss of the NSL complex in neural cells causes widespread metabolic defects, including an accumulation of free long-chain fatty acids (LCFAs). Free LCFAs induce a Toll-like receptor 4 (TLR4)-NFκB-dependent pro-inflammatory signalling cascade in neighbouring vascular pericytes that is rescued by TLR4 inhibition. Pericytes display functional changes in response to LCFA-induced activation that result in vascular breakdown. Our work establishes that neurovascular function is determined by the neural metabolic environment.

U2 - 10.1038/s41556-020-0526-8

DO - 10.1038/s41556-020-0526-8

M3 - SCORING: Journal article

C2 - 32541879

VL - 22

SP - 828

EP - 841

JO - NAT CELL BIOL

JF - NAT CELL BIOL

SN - 1465-7392

IS - 7

ER -