en
  • Deutsch - de
  • English - en
  • About
      About us
        Our Measures
          Members
            Cluster Management
               PhD & Postdoc representatives
                Scientific Advisory Board
                   International cooperation partners
                    Timeline
                       Media Kit
                        Contact
                      • News & Events
                          News
                            Events
                              In the News
                                Open Positions
                              • Research
                                  Publications
                                    Our Research Focus
                                      Technology Hubs
                                        Research Spotlight
                                          Data Management & Sharing
                                            Sustainability Initiative
                                               Code of Conduct
                                            • Science & Society
                                                For Schools & Students
                                                  Public Events
                                                    Podcasts
                                                      Videos
                                                    • Support for Diversity & Equity
                                                        Newcomer Center
                                                          Gender Equality Program
                                                            Early Career Investigator Program
                                                          1. Home
                                                          2. News & Events
                                                          3. News
                                                          4. Key mechanisms identified for improving astrocyte-to-neuron reprogramming
                                                          News | 10/07/2024 | Research Spotlight

                                                          Key mechanisms identified for improving astrocyte-to-neuron reprogramming

                                                          Researchers have made significant progress in unraveling novel mechanisms of glia-to-neuron conversion. Using novel methods in epigenome profiling, they identified that a posttranslational modification of the reprogramming neurogenic transcription factor profoundly impacts epigenetic rewiring and the improvement in neuronal programming. They identified a novel protein as key player in this conversion process, namely the transcriptional regulator YingYang1 that physically interacts with the neurogenic factor to open up the chromatin. These novel insights reveal how the conversion at the molecular level works and pave the way to improve the reprogramming of glial cells into neurons.
                                                          Copyright unknown

                                                          This is a summary of Pereira, A., Diwakar, J., Masserdotti, G. et al. Direct neuronal reprogramming of mouse astrocytes is associated with multiscale epigenome remodeling and requires Yy1. published in Nature Neuroscience (2024). https://doi.org/10.1038/s41593-024-01677-5


                                                          The challenge

                                                          Neurological disorders, such as trauma, stroke, epilepsy, and various neurodegenerative diseases, often lead to the permanent loss of neurons, causing significant impairments in brain function. The current treatment options are limited, primarily due to the challenge of replacing lost neurons. Direct neuronal reprogramming, a complex procedure that involves changing the function of one type of cell into another, offers a promising strategy for neuron replacement. In laboratory settings and living organisms, glial cells, the non-neuronal cells in the central nervous system, have been successfully transformed into functional neurons. However, the processes involved in neuronal reprogramming, including the role of transcription factors and the epigenome, are complex and require further understanding. This complexity presents a challenge and motivation for researchers in neuroscience and regenerative medicine, which is why we set out to study the conversion at the molecular level.


                                                          Our approach

                                                          We focused on changes and modifications in the epigenome. We combined single-cell multiomics with genome-wide profiling of 3D nuclear architecture and DNA methylation in mouse astrocyte-to-neuron reprogramming. We compared transcription factors with different reprogramming efficiencies to link epigenome remodeling with the outcome of mouse astrocyte-to-neuron reprogramming. We looked at the neurogenic activity of Ngn2 and its phosphorylation-resistant form (PmutNgn2).


                                                          Our findings

                                                          We identified that the phosphorylation-resistant form of the reprogramming neurogenic transcription factor Neurogenin2 profoundly improved the epigenetic rewiring and neuronal reprogramming. In addition, we found that one of the factors predominatly up-regualted by the phosphorylation-resistant form of Ngn2 proved to be an essential co-factor to reprogram the glial cells into neurons. This is the transcriptional regulator YingYang1 that is necessary to open up the chromatin for reprogramming, to which end it interacts with the transcription factor. The protein is crucial for achieving the conversion from astrocytes to neurons.


                                                          The implications

                                                          These findings are important to understand and improve the reprogramming of glial cells to neurons and thus bring us closer to therapeutic solutions.


                                                          Creating SyNergies

                                                          The study was led by Magdalena Götz, Head of the Stem Cell Center Department at Helmholtz Munich and the division of Physiological Genomics at the Biomedical Center, LMU, as well as Boyan Bonev from the Helmholtz Pioneer Campus. Within the SyNergy network, we will now explore this improved reprogramming paradigm in pathology in vivo, such as stroke or traumatic brain injury. 


                                                          Participating Universities
                                                           LMU logo in white
                                                           TUM logo in white
                                                          Partner Institutions
                                                           Logo DZNE in white
                                                          Helmholtz Munich logo in white 
                                                           Logo Max Planck Gesellschaft 

                                                          SyNergy is funded by the Deutsche Forschungsgemeinschaft (German Research Foundation) within the framework of the German Excellence Strategy (EXC 2145 SyNergy – ID 390857198). The Excellence Strategy promotes outstanding research at German universities. 

                                                          Contact

                                                          Munich Cluster for Systems Neurology (SyNergy)

                                                          Feodor-Lynen-Str. 17
                                                          81377 Munich
                                                          +49 (0)89 4400-46497
                                                          yüubgybcјuipxјrvfulyztmi
                                                          Login for editors
                                                          Imprint | Data-Safety
                                                          en
                                                          • Deutsch - de
                                                          • English - en

                                                          Home

                                                          • About
                                                            • About us
                                                            • Our Measures
                                                            • Members
                                                            • Cluster Management
                                                            •  PhD & Postdoc representatives
                                                            • Scientific Advisory Board
                                                            •  International cooperation partners
                                                            • Timeline
                                                            •  Media Kit
                                                            • Contact
                                                          • News & Events
                                                            • News
                                                            • Events
                                                            • In the News
                                                            • Open Positions
                                                          • Research
                                                            • Publications
                                                            • Our Research Focus
                                                            • Technology Hubs
                                                            • Research Spotlight
                                                            • Data Management & Sharing
                                                            • Sustainability Initiative
                                                            •  Code of Conduct
                                                          • Science & Society
                                                            • For Schools & Students
                                                            • Public Events
                                                            • Podcasts
                                                            • Videos
                                                          • Support for Diversity & Equity
                                                            • Newcomer Center
                                                            • Gender Equality Program
                                                            • Early Career Investigator Program