CO23: Genetics and Neurodegenerative Diseases

The Genetics and Neurodegenerative Diseases group aims to discern the main genetic pathways affected in Parkinson's disease and other neurodegenerative disorders. To do this, we will use single cell RNA sequencing, which will allow us to describe the main genetic alterations with cell type specificity, using both postmortem brain tissue from patients and cells from samples of peripheral fluids donated by patients. as tissue animal models. The data will be validated using histological techniques such as immunofluorescence and in situ hybridization, and spatial transcriptomics techniques such as in situ sequencing. The high sensitivity of the techniques used will allow us to determine the most affected cell types and which genes are most involved, which will guide the exploration of new therapeutic targets and treatment pathways.

The group is a mixed group of basic researchers (3) and clinical researchers (3). The basic researchers are: the head of the group, Ana Muñoz Manchado, a Ramón y Cajal researcher at the UCA, an expert in single cell transcriptome sequencing and associated techniques, and two doctoral students who will join her in the coming months. Together they will gather the necessary skills for the generation of single cell transcriptome data and their bioinformatic analysis. One of the doctoral students is associated with a FPI of the UCA's own plan for Ramones y Cajales, and the other doctoral student with the FPI associated with the Ministry's project granted to the group leader. Both calls are closed and the selection process is underway. The other 3 members of the group are clinical researchers (medical specialists in Neurology): Andrés, Beatriz and Alicia, belonging to the Neurology Service of the Puerta del Mar University Hospital, with access to patient samples, and who will provide the necessary knowledge to relate the genetic data with the symptomatic pictures of the patients, anatomical and histological alterations. With this mixture and diversity of knowledge, we aspire to establish a direct bridge between basic and clinical research in a group of diseases, such as neurodegenerative diseases, with a high social and economic impact.

• Ana Belén Muñoz Manchado:
• E-mail: ana.munoz@uca.es.
• ORCID: 0000-0002-1121-6072.

• Regulatory genetic networks of Parkinson's disease. Responsible: Ana B. Muñoz Manchado.

Neurodegenerative diseases Parkinson Single cell sequencing Fluted Transcriptome

• Principal Investigators:
  • Ana Belén Muñoz Manchado (PI).
• Investigators:
  • Andrés Hermosín Gómez (Medical researcher specialized in Neurology).
• Predoctoral Researchers:
  • Juan Manuel Barba Reyes.
  • Mónica Díez Salguero.

• Ministerio de Ciencia e Innovación. Proyectos de I+D+I, 2019, Retos Investigación y Generación del Conocimiento. PID2019-109046GA-I00. Redes Genéticas Reguladoras en la Enfermedad de Parkinson. PI: Ana Muñoz.
• Programa Ramón y Cajal. Ministerio de Ciencia e Innovación. Gobierno de España. PI: Ana Muñoz.

1. Munguba, H; Chattopadhyaya, B; Nilsson, S; Carrico, JN; Memic, F; Oberst, P; Batista-Brito, R; Munoz-Manchado, AB; Wegner, M; Fishell, G; Di Cristo, G; Hjerling-Leffler, J-Postnatal Sox6 Regulates Synaptic Function of Cortical Parvalbumin-Expressing Neurons-JOURNAL OF NEUROSCIENCE-2021-41-438876-8886--10.1523/JNEUROSCI.0021-21.2021. QJCR2020:Q1-6,167.

1. [All are Q1 magazines].

1. Qian X, Harris KD, HAuling T, Nicoloutsopoulos D, Muñoz-Manchado AB, Skene N, Hjerling-Leffler J, Nilsson M. Probabilistic cell typing enables fine mapping of closely related cell types in situ. Nature Methods, 2020; 17(1):101-106. PMID: 31740815. IF: 30.822.

1. [All are Q1 magazines].

1. Jansen PR, Watanabe K, Stringer S, Skene N, Bryois J, Hammerschlag AR, de Leeuw CA, Benjamins JS, Muñoz-Manchado AB, Nagel M, Savage JE, Tiemeier H, White T; 23andMe Research Team, Tung JY, Hinds DA, Vacic V, Wang X, Sullivan PF, van der Sluis S, Polderman TJC, Smit AB, Hjerling-Leffler J, Van Someren EJW, Posthuma D. Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways. Nature Genetics. 2019; 51(3):394-403. PMID: 30804565. IF: 31.077.

1. [All are Q1 magazines].

1. Muñoz-Manchado AB*, Bengtsson-Gonzales C*, Zeisel A*, Munguba H, Bekkouche B, Skene NG, Lonnerberg P, Ryge J, Harris K, Linnarsson, S, Hjerling-Leffler J. Diversity of interneurons in the dorsal striatum revealed by single-cell RNA-sequencing and PatchSeq. Cell Reports 2018, 21;24(8):2179-2190.e7. PMID: 30134177. IF: 7.815.
2. Savage JE et al (118/27). Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence. Nature Genetics. 2018;50(7):912-919. PMID: 29942086. IF: 31.077.
3. Nagel M, Jansen PR, Stringer S, Watanabe K, de Leeuw CA, Bryois J, Savage JE, Hammerschlag AR, Skene NG, Muñoz-Manchado AB; 23andMe Research Team, White T, Tiemeier H, Linnarsson S, Hjerling-Leffler J, Polderman TJC, Sullivan PF, van der Sluis S, Posthuma D. Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways. Nature Genetics. 2018 50(7):920-927. doi: 10.1038/s41588-018-0151-7. PMID: 29942085. IF: 31.077.
4. Skene NG, Bryois J, Bakken TE, Breen G, Crowley JJ, Gaspar H, Giusti-Rodriguez P, Hodge RD, Miller JA, Muñoz-Manchado AB, O'Donovan MC, Owen MJ, Pardinas AF, Ryge J, Walters JTR, Linnarsson S, Lein EdS, Sullivan PF, Hjerling-Leffler J.“Genetic identification of brain cell types underlying schizophrenia”. Nature Genetics, 2018, 50(6):825-833. PMID: 29785013. IF: 31.077.
5. Coleman JRI, Bryois J, Gaspar HA, Jansen PR, Savage JE, Skene N, Plomin R, Muñoz-Manchado AB, Linnarsson S, Crawford G, Hjerling-Leffler J, Sullivan PF, Posthuma D, Breen G. “Biological annotation of genetic loci associated with intelligence in a meta-analysis of 87,740 individuals”. Molecular Psychiatry, 2018. PMID: 29520040. IF:11.973.
6. Perez-Villalba A, Sirerol-Piquer MS, Belenguer G, Soriano-Cantón R, Muñoz-Manchado AB, Villadiego J, Alarcón-Arís D, Soria FN, Dehay B, Bezard E, Vila M, Bortolozzi A, Toledo-Aral JJ, Pérez-Sánchez F, Fariñas I. “Synaptic Regulator α-Synuclein in Dopaminergic Fibers Is Essentially Required for the Maintenance of Subependymal Neural Stem Cells”. Journal of Neuroscience, 2018, Jan 24; 38(4): 814-825. PMID: 29217686. IF: 6.074.

1. * Equal contributions.

1. [All are Q1 magazines].

1. Nguyen HT, Bryois J, Kim A, Dobbyn A, Huckins LM, Muñoz-Manchado AB, Ruderfer DM, Genovese G, Fromer M, Xu X, Pinto D, Linnarsson S, Verhage M, Smit AB, Hjerling-Leffler J, Buxbaum JD, Hultman C, Sklar P, Purcell SM, Lage K, He X, Sullivan PF, Stahl EA. Integrated Bayesian analysis of rare exonic variants to identify risk genes for schizophrenia and neurodevelopmental disorders. Genome Medicine, 2017, 20; 9(1): 114. PMID:29262854. IF: 8.898.

1. [All are Q1 magazines].

1. Muñoz-Manchado AB, Villadiego J, Romo-Madero S, Suarez-Luna N, Bermejo-Navas A, Rodriguez-Gomez JA, Garrido-Gil P, Labandeira-Garcia JL, Echevarria M, Lopez-Barneo J, Toledo-Aral JJ. Chronic and progressive Parkinson's disease MPTP model in adult and aged mice. Journal of Neurochemistry, 2016, 136; 2 373-87. PMID: 26500044. IF: 4.083.
2. Muñoz-Manchado AB*, Foldi C*, Szydlowski S*, Sjulson L, Farries M, Wilson C, Silberberg G, Hjerling-Leffler J. Novel Striatal GABAergic Interneuron Populations Labeled in the 5HT3a(EGFP) Mouse. Cerebral cortex, 2016, 26;1 96-105. PMID: 25146369. IF:8.665.
3. Marques S, Zeisel A, Codeluppi S, van Bruggen D, Mendanha Falcão A, Xiao L, Li H, Häring M, Hochgerner H, Romanov RA, Gyllborg D, Muñoz-Manchado AB, La Manno G, Lönnerberg P, Floriddia EM, Rezayee F, Ernfors P, Arenas E, Hjerling-Leffler J, Harkany T, Richardson WD, Linnarsson S, Castelo-Branco G. Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system. Science, 2016, 352; 6291 1326-9. PMID: 27284195. IF: 37.205.

1. * Equal contributions.

1. [All are Q1 magazines].

1. Zeisel A*, Muñoz-Manchado AB*, Codeluppi S, Lönnerberg P, La Manno G, Juréus A, Marques S, Munguba H, He L, Betsholtz C, Rolny C, Castelo-Branco G, Hjerling-Leffler J, Linnarsson S. Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science, 2015, 347; 6226 1138-42. PMID: 25700174. IF: 34.665.

1. * Equal contributions.

1. [All are Q1 magazines].

1. Ortega-Saenz P, Pardal R, Levitsky K, Villadiego J, Muñoz-Manchado AB, Duran R, Bonilla-Henao V, Arias-Mayenco I, Sobrino V, Ordonez A, Oliver M, Toledo-Aral JJ, Lopez-Barneo J. Cellular properties and chemosensory responses of the human carotid body. Journal of Physiology, 2013, 591;24 6157-73. PMID: 24167224. IP:4.544.
2. Muñoz-Manchado AB*, Villadiego J*, Suarez-Luna N, Bermejo-Navas A, Garrido-Gil P, Labandeira-Garcia JL, Echevarria M, Lopez-Barneo J, Toledo-Aral JJ. Neuroprotective and reparative effects of carotid body grafts in a chronic MPTP model of Parkinson's disease. Neurobiology of Aging, 2013, 34;3 902-15. PMID: 22743091. IF:4.853.

1. * Equal contributions.

1. [All are Q1 magazines].

1. Rodriguez-Pallares J, Joglar B, Muñoz-Manchado AB, Villadiego J, Tolde-Aral JJ, Labandeira-Garcia JL. Cografting of carotid body cells improves the long-term survival, fiber outgrowth and functional effects of grafted dopaminergic neurons. Regenerative Medicine, 2012, 7;3 309-22. PMID: 22594325. IF:3.873.