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EPIScOPE SIGNED

Reversing the epigenetic state of oligodendrocyte precursors cells in multiple sclerosis

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EC-Contrib. €

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Project "EPIScOPE" data sheet

The following table provides information about the project.

Coordinator
KAROLINSKA INSTITUTET 

Organization address
address: Nobels Vag 5
city: STOCKHOLM
postcode: 17177
website: www.ki.se

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Sweden [SE]
 Total cost 1˙895˙155 €
 EC max contribution 1˙895˙155 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-CoG
 Funding Scheme ERC-COG
 Starting year 2016
 Duration (year-month-day) from 2016-09-01   to  2021-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KAROLINSKA INSTITUTET SE (STOCKHOLM) coordinator 1˙895˙155.00

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 Project objective

Oligodendrocytes (OL) are glial cells that mediate myelination of neurons, a process that is defective in multiple sclerosis (MS). Although OL precursor cells (OPCs) can initially promote remyelination in MS, this regenerative mechanism eventually fails in progressive MS. OPCs go through several epigenetic states that ultimately define their potential to differentiate and myelinate. OPCs in progressive MS stall in a distinct epigenetic state, incompatible with differentiation and remyelination. We hypothesize that these OPCs regress to an epigenetic state reminiscent of the state of embryonic OPCs, which remain undifferentiated. In this proposal, we aim to uncover the causes behind the remyelination failure upon disease progression in MS. We will determine the epigenetic/transcriptional states of OPCs during development and in MS, using single cell and bulk RNA sequencing and quantitative proteomics. We will further investigate how the interplay between transcription factors (TFs), chromatin modifiers (ChMs) and non-coding RNAs (ncRNAs) contributes to the transition between epigenetic states of OPCs. The results will allow the identification of ChMs and ncRNAs that can modulate these states and thereby control OPC differentiation and myelination. We will use this knowledge to investigate whether we can reverse the epigenetic state of OPCs in MS, in order to promote their differentiation and remyelination. The unique combination of leading-edge techniques such as SILAC coupled with immunoprecipitation and mass-spectrometry, single-cell RNA sequencing, ChIP-Sequencing, among others, will allow us to provide insights into novel epigenetic mechanisms that might be underlying the effects of environmental and lifestyle risk factors for MS. Moreover, this project has the potential to lead to the discovery of new targets for epigenetic-based therapies for MS, which could provide major opportunities for improved clinical outcome of MS patients in the near future.

 Publications

year authors and title journal last update
List of publications.
2017 David van Bruggen, Eneritz Agirre, Gonçalo Castelo-Branco
Single-cell transcriptomic analysis of oligodendrocyte lineage cells
published pages: 168-175, ISSN: 0959-4388, DOI: 10.1016/j.conb.2017.10.005
Current Opinion in Neurobiology 47 2019-06-18
2019 Sarah Jäkel, Eneritz Agirre, Ana Mendanha Falcão, David van Bruggen, Ka Wai Lee, Irene Knuesel, Dheeraj Malhotra, Charles ffrench-Constant, Anna Williams, Gonçalo Castelo-Branco
Altered human oligodendrocyte heterogeneity in multiple sclerosis
published pages: 543-547, ISSN: 0028-0836, DOI: 10.1038/s41586-019-0903-2
Nature 566/7745 2019-04-14
2018 Ana Mendanha Falcão, David van Bruggen, Sueli Marques, Mandy Meijer, Sarah Jäkel, Eneritz Agirre, Samudyata, Elisa M. Floriddia, Darya P. Vanichkina, Charles ffrench-Constant, Anna Williams, André Ortlieb Guerreiro-Cacais, Gonçalo Castelo-Branco
Disease-specific oligodendrocyte lineage cells arise in multiple sclerosis
published pages: 1837-1844, ISSN: 1078-8956, DOI: 10.1038/s41591-018-0236-y
Nature Medicine 24/12 2019-04-14
2018 Gioele La Manno, Ruslan Soldatov, Amit Zeisel, Emelie Braun, Hannah Hochgerner, Viktor Petukhov, Katja Lidschreiber, Maria E. Kastriti, Peter Lönnerberg, Alessandro Furlan, Jean Fan, Lars E. Borm, Zehua Liu, David van Bruggen, Jimin Guo, Xiaoling He, Roger Barker, Erik Sundström, Gonçalo Castelo-Branco, Patrick Cramer, Igor Adameyko, Sten Linnarsson, Peter V. Kharchenko
RNA velocity of single cells
published pages: 494-498, ISSN: 0028-0836, DOI: 10.1038/s41586-018-0414-6
Nature 560/7719 2019-04-14
2018 Sueli Marques, David van Bruggen, Darya Pavlovna Vanichkina, Elisa Mariagrazia Floriddia, Hermany Munguba, Leif Väremo, Stefania Giacomello, Ana Mendanha Falcão, Mandy Meijer, Åsa Kristina Björklund, Jens Hjerling-Leffler, Ryan James Taft, Gonçalo Castelo-Branco
Transcriptional Convergence of Oligodendrocyte Lineage Progenitors during Development
published pages: 504-517.e7, ISSN: 1534-5807, DOI: 10.1016/j.devcel.2018.07.005
Developmental Cell 46/4 2019-04-14

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