EPIScOPE SIGNED
Reversing the epigenetic state of oligodendrocyte precursors cells in multiple sclerosis
Total Cost €
0EC-Contrib. €
0Partnership
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Explore the words cloud of the EPIScOPE project. It provides you a very rough idea of what is the project "EPIScOPE" about.
Project "EPIScOPE" data sheet
The following table provides information about the project.
| Coordinator |
KAROLINSKA INSTITUTET
Organization address contact info |
| 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.
| # | ||||
|---|---|---|---|---|
| 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 |
|---|---|---|---|
| 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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