Expansion of the neocortex and protection from neurodegeneration by in vivo transient reprogramming
Yamanaka factors (YFs) can reverse some aging features in mammalian tissues, but their effects on the brain remain largely unexplored. Here, we induced YFs in the mouse brain in a controlled spatiotemporal manner in two different scenarios: brain development and adult stages in the context of neurodegeneration. Embryonic induction of YFs perturbed cell identity of both progenitors and neurons, but transient and low-level expression is tolerated by these cells. Under these conditions, YF induction led to progenitor expansion, an increased number of upper cortical neurons and glia, and enhanced motor and social behavior in adult mice. Additionally, controlled YF induction is tolerated by principal neurons in the adult dorsal hippocampus and prevented the development of several hallmarks of Alzheimer's disease, including cognitive decline and altered molecular signatures, in the 5xFAD mouse model. These results highlight the powerful impact of YFs on neural proliferation and their potential use in brain disorders.
Authors
- Albert Giralt (ORCID: https://orcid.org/0000-0001-5334-0963)
- Laia Richart (ORCID: https://orcid.org/0000-0003-4593-3229)
- Daniel del Toro (ORCID: https://orcid.org/0000-0002-7416-2155)
- Jordi Alberch (ORCID: https://orcid.org/0000-0002-8684-2721)
- Josep M. Canals (ORCID: https://orcid.org/0000-0001-6829-7670)
- Anna Sancho‐Balsells (ORCID: https://orcid.org/0000-0003-2053-7211)
- Seung Hee Chun (ORCID: https://orcid.org/0009-0008-2225-3267)
- Vipul Gupta (ORCID: https://orcid.org/0000-0001-9738-7181)
- G. Seyit-Bremer
- Iván Ballasch (ORCID: https://orcid.org/0000-0001-9625-5144)
- María Abad (ORCID: https://orcid.org/0000-0002-1462-2498)
- Manuel Serrano (ORCID: https://orcid.org/0000-0001-7177-9312)
- Rüdiger Klein (ORCID: https://orcid.org/0000-0002-3109-0163)
- Noelia Alcázar
- Tobias Straub (ORCID: https://orcid.org/0000-0002-0547-0453)
- Carmen Cifuentes-Díaz (ORCID: https://orcid.org/0000-0003-2563-2082)
- Sofía Zaballa
- Hao‐Yi Li (ORCID: https://orcid.org/0000-0002-9739-5365)
- Yiru Shen (ORCID: https://orcid.org/0000-0002-7263-1632)
- Jordi Abante (ORCID: https://orcid.org/0000-0003-4137-2858)
- Irene Rodríguez-Navarro (ORCID: https://orcid.org/0000-0002-1863-2124)
- Xavier Bech
- Iñaki Merino-Valverde
Institutions
- National Sun Yat-sen University (TW)
- Inserm (FR)
- Sorbonne Université (FR)
- Granta Design (United Kingdom) (GB)
- Institute for Research in Biomedicine (ES)
- Institut d'Investigacions Biomèdiques de Barcelona (ES)
- Barcelona Institute of Science and Technology (ES)
- Institut du Fer à Moulin (FR)
- Max Planck Institute of Neurobiology (DE)
- Max Planck Institute of Biochemistry (DE)
- CIBBIM-Nanomedicine (ES)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Cell stem cell
- Published
- 2024-10-18
- DOI
- https://doi.org/10.1016/j.stem.2024.09.013
- Citations
- 13
- Primary Topic
- Pluripotent Stem Cells Research
- Type
- article
- Field-Weighted Citation Impact
- 3.04
Funders
- Fundación Ramón Areces
- Max-Planck-Gesellschaft
- Ministerio de Ciencia e Innovación