LABORATORIES
Stem cells, neurogenesis and neurodegeneration
Stem cells, neurogenesis and neurodegeneration
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PRE- AND POST-DOCTORAL CANDIDATES ARE SOUGHT TO APPLY FOR WORK
in the frame of the project: In vivo study of neuronal dysfunction and degeneration in Parkinson’s and Alzheimer’s diseases through transplantation of brain organoids derived from iPSCs”. Reference: PID2022-137076OB-I00.
Research
The research of our group is focused on studying the cellular, molecular and genetic mechanisms involved in three fundamental processes: 1) the differentiation and maturation of human neurons and astrocytes obtained from iPSCs derived from healthy subjects; 2) the alterations of these events that could result in neurodevelopmental disorders, and that could also underlie early steps in the aetiology of Parkinson´s disease (PD) and Alzheimer´s disease (AD); and 3) the neurodegenerative processes in PD and AD, and the search for new mechanisms and molecular targets in iPSC-derived neurons and glia obtained from patients.
Our current research lines are:
1.Studying the mechanisms of neurodegeneration and neuroprotection in Parkinson’s disease (PD) and Alzheimer’s disease (AD) using technologies based on iPSCs.
1.1. To study the impact of mutations in the GBA1 gene (risk factors for sporadic PD), the APOE-ε4 allele (a risk factor for sporadic AD), and the G206D-PSEN1 mutation (a causative factor for familial AD), on cell dysfunction and neurodegeneration, using 2D, 3D (cerebral organoids) cultures and transplantation.
1.2. To find new molecular targets and strategies for restoring the healthy neuronal and astrocyte phenotypes in PD and AD. We will search for molecular targets and analyze PD and AD brains to confirm the in vivo expression of the proposed targets and their cellular and subcellular localization.
2.The regulation of neurogenesis, gliogenesis, and cell maturation as studied from human iPSCs and mouse NSCs using cell culture and in vivo approaches.
2.1. To explore the mechanisms regulating the differentiation and maturation of human neurons (dopaminergic, hippocampal, cerebro-cortical) and astrocytes derived from iPSCs of healthy subjects and PD and AD patients.
2.2. To study the role of insulin-like growth factor-I (IGF-I) and TBR1 transcription factor during neurogenesis, gliogenesis, and neurological disorders.
Contributions from our group:
1) Isolation of cells from the embryonic and adult olfactory bulb (OB) with characteristics of neural stem cells (NSCs) that generate mature neurons in culture and in vivo.
2) Results from our laboratory suggest that embryonic OB progenitor cells (expressing Dlx2 and Pax6) contribute to the generation of GABAergic and dopaminergic neurons in vivo.
3) IGF-I growth factor and PTEN phosphatase regulate OB NSC proliferation and differentiation by controlling P-AKT levels.
4) Our studies indicate that IGF-I could have an important role during the migration and incorporation of new neurons in the OB and in the Hipocampal Dentate Gyrus.
Brain IGFI-I regulates spatial memory and sexual dimorphic behaviour.
5) The expression of the transcription factor Tbr1 seems key for the regulation of neurons and glial cells from NSCs and neural progenitors in the OB.
Tbr-1 has a key role during neuronal development in the Cerebral Cortex.
6) We have obtained 14 induced pluripotent stem cells (iPSCs) by reprogramming fibroblasts from Parkinson´s disease patients, Alzheimer´s disease patients and control individuals.
7) We have participated in the European Proyect “ADAPTED” to obtain isogenic iPSCs with the goal of studying the impact of APOE polymorphism on
Alzheimer´s disease. In the frame of the european project “ADAPTED”.
8) Generation of mature-functional neurons (dopaminergic, hipocampal and cerebral cortical) from human iPSCs.
9) Generation of Astrocytes from human iPSCs.
10) We have been the first to demonstrate the graphene biocompatibility with neurons and glial cells. In the frame of the european project “HARCANA”.
Experimental approaches
- Cultures of embryonic and adult neural stem cells (NSCs).
- Cultures of neurons for studies of differentiation, maturation and synaptogenesis.
- Slice cultures for migration studies.
- Use of transgenic mice and knockouts.
- Cell reprogramming to obtain iPSCs from human fibroblasts.
- Generation of mature neurons and astrocytes.
- Cell transplants in the embryonic, postnatal and adult brain.
- Expression of transcription factors in stem and progenitor cells in vivo and in culture.
- Cell cytometry and sorting.
- Cellular, molecular, genetic, inmuno-neurohistochemistry, neurochemistry, and microscopy – imaging studies.
- Isolation and reprogramming of human fibroblasts into iPS cells and neurons.
- Advanced cell imaging and morphological analysis.
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Development of brain organoid cultures from iPSCs.
Team
Carlos Vicario Abejón
CSIC Senior Scientist and Principal Investigator
Rebeca Vecino Pérez
Postdoctoral Fellow
Francisco José Fernández Acosta
PhD student
Mª José Román Alonso
Laboratory Technician
Daniel Flores Téllez
JAE-Intro fellow
María Galán Vázquez
Master student
Miriam Sánchez Calvo
Master student
Elena Palencia Moratalla
Master student
Marta González González
Master student
Publications
Publications of the last 10 years
NOTA: A LO LARGO DE MI CARRERA INVESTIGADORA, HE FIRMADO MIS ARTÍCULOS COMO CARLOS VICARIO Y COMO CARLOS VICARIO-ABEJÓN.
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- 1. Costa-Laparra I, Juárez-Escoto E, Vicario C, Moratalla R*, García-Sanz P* (2023). APOE epsilon4 allele, along with G206D–PSEN1 mutation, alters mitochondrial networks and their degradation in Alzheimer’s disease. Frontiers in Aging Neuroscience 15: 1087072 (pages 1-19). doi: 10.3389/fnagi.2023.1087072. PMID: 37455931. F.I. = 5.70. Q1.
- 2. Herrero-Labrador R*, Fernández-Irigoyen J*, Vecino R*, González-Arias C, Ausín K, Crespo I, Fernández Acosta FJ, Nieto-Estévez V, Román MJ, Perea G, Torres-Alemán I, Santamaría E, Vicario C (2023). Brain IGF-I regulates LTP, spatial memory and sexual dimorphic behavior. Life Science Alliance 6: e202201691 (pages 1-19). doi: 10.26508/lsa.202201691. PMID: 37463753. F.I. = 5,78. Q1
- 3. Fernández Acosta FJ, Luque-Molina, I, Vecino R,…, Vicario C. (2022) Morphological diversity of Calretinin interneurons generated from adult olfactory bulb core neural stem cells. Frontiers in Cell and Developmental Biology 10: 932297. https://doi.org/10.3389/fcell.2022.932297. PMID: 35846352. I.F. = 6,08. Q1
- 4. Crespo I, Pignatelli J, Kinare V, Méndez-Gómez HR,…, Tole S, Vicario C. (2022 Jul 4) Tbr1 misexpression alters neuronal development in the cerebral cortex. Molecular Neurobiology. https://doi.org/10.1007/s12035-022-02936-x. PMID: 35781633. I.F. = 5,59. Q1
- 5. Li L, …, Vicario C. , Silvia K.,…, Mira H, Morales AV. (2022). SoxD genes are required for adult neural stem cell activation. Cell Reports 38, 110313. I.F. = 9,42. Q1
- 6. Nieto-Estévez V, Defteralı C, Vicario C. (2022). Distinct effects of BDNF and NT-3 on the dendrites and presynaptic boutons of developing olfactory bulb GABAergic interneurons in vitro. Cellular and Molecular Neurobiology 42(5):1399-1417. https://doi.org/10.1007/s10571-020-01030-x. PMID: 33392918. I.F. = 5,05. Q1
- 7. Defteralı C, …, Vicario C. Neural stem cells in the adult olfactory bulb core generate mature neurons in vivo (2021). Stem Cells https://doi.org/10.1002/stem.3393. PMID: 33963799. I.F. = 6,02. Q1.
- 8. Schmid B, …, Vicario C. , …,Cabrera-Socorro A (2021). Generation of a set of isogenic iPSC lines carrying all APOE genetic variants (Ɛ2/Ɛ3/Ɛ4) and knock-out for the study of APOE biology in health and disease. Stem Cell Research 52: 102180 (pp. 1-5). https://doi.org/10.1016/j.scr.2021.102180. PMID: 33556820. I.F. = 4,49. Q1.
- 9. Rodríguez-Traver E, Díaz-Guerra E,…, Vicario C. (2020). A collection of three integration-free iPSCs derived from old male and female healthy subjects. Stem Cell Research 42: 101663 (pp. 1-6). https://doi.org/10.1016/j.scr.2019.101663. PMID: 31794941. I.F. = 4,49. Q1.
- 10. Díaz-Guerra E,…, Vicario C. (2019). A collection of four integration-free iPSC lines derived from diagnosed sporadic Alzheimer´s disease patients with different APOE alleles. Stem Cell Research 39: 101522 (pp. 1-6). https://doi.org/10.1016/j.scr.2019.101522. PMID: 31401456. I.F. = 4,49. Q1.
- 11. Rodríguez-Traver E,…, Moratalla R, Vicario C. (2019). A collection of integration-free iPSCs derived from Parkinson´s disease patients carrying mutations in the GBA1 gene. Stem Cell Research 38: 101482 (pp. 1-6). https://doi.org/10.1016/j.scr.2019.101482. PMID: 31203165. I.F. = 4,49. Q1.
- 12. García-Sanz P,…, Vicario C. , Moratalla R (2018). Cholesterol and multilamellar bodies: Lyosomal dysfunction in GBA-Parkinson disease. Autophagy 14:717-718. PMID: 29368986. I.F. = 11,06. Q1 and D1.
- 13. García-Sanz P,…, Vicario C. #, Moratalla R# (Co-Senior authors) (2017). N370S-GBA1 mutation causes lysosomal cholesterol accumulation in Parkinson´s Disease. Movement Disorders 32:1409-1422. PMID: 28779532. I.F. = 8,32. Q1 and D1.
- 14. Defterali C, …, Vicario-Abejón C. (2016). Thermally reduced graphene is a permissive material for neurons and astrocytes and de novo neurogenesis in the adult olfactory bulb in vivo. Biomaterials 82:84-93. PMID: 26751821. I.F. = 8,89. Q1 and D1.
- 15. Nieto-Estévez V, …, Vicario-Abejón C. (2016). Brain insulin-like growth factor-I directs the transition from stem cells to mature neurons during postnatal/adult hippocampal neurogenesis. Stem Cells 34:2194-2209. PMID: 27144663. I.F. = 5,64. Q1 and D1.
- 16. Nieto-Estévez V, Defterali Ç, Vicario-Abejón C. (2016). IGF-I: A key growth factor that regulates neurogenesis and synaptogenesis from embryonic to adult stages of the brain. Frontiers in Neuroscience 10: article 52; (pages 1-9). PMID: 26941597 I.F. = 5,15. Q1.
- 17. Rodríguez-Traver E, …, Moratalla R, Vicario-Abejón C. (2016). Role of Nurr1 in the generation and differentiation of dopaminergic neurons from stem cells. Neurotoxicity Research 30:14-31. PMID: 26678495. I.F. = 3,14. Q1.
- 18. Defterali C, Verdejo R, …, López-Manchado MA, Vicario-Abejón C. (2016). In vitro evaluation of biocompatibility of uncoated thermally reduced graphene and carbon nanotube-loaded PVDF membranes with adult neural stem cell-derived neurons and glia. Frontiers in Bioengineering and Biotechnology 4: Article 94 (pages 1-19). PMID: 27999773. I.F. = 4,36. Q1 y D1.
Contact
Where to find us
Laboratory of stem cells, neurogenesis and neurodegeneration
Instituto Cajal CSIC. Avda. Doctor Arce, 37. 28002. Madrid
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Additional information
Doctoral Thesis Supervised
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TITLE: “Células multipotentes y progenitores en el Sistema Nervioso Central: Señales de supervivencia y diferenciación durante el desarrollo”. PhD STUDENT: Mª José Yusta Boyo. DISSERTATION: 24-septiembre-2003. ACADEMIC GRADE: Sobresaliente cum laude por unanimidad.
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TITLE: “Generación de interneuronas GABAérgicas y dopaminérgicas a partir de células madre y precursores de bulbo olfatorio embrionario y adulto”. PhD STUDENT: Eva Vergaño Vera. DISSERTATION: 3-octubre-2006. ACADEMIC GRADE: Apto cum laude por unanimidad.
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TITLE: “Rutas de señalización moduladoras de proliferación y diferenciación en células madre y precursores neurales”. PhD STUDENT: Gaizka Otaegi García. DISSERTATION: 19-octubre-2006. ACADEMIC GRADE: Sobresaliente cum laude por unanimidad.
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TITLE: “Factores de transcripción en el desarrollo del telencéfalo: Efectos de Tbr1 y Gsx2 en células madre y progenitores neurales”. PhD STUDENT: Héctor Rubén Méndez Gómez. DISSERTATION: 21-diciembre-2009. ACADEMIC GRADE: Sobresaliente cum laude por unanimidad.
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TITLE: “Papel de IGF-I en la migración y neurogénesis de la zona subventricular y el bulbo olfatorio”. PhD STUDENT: Anahí Hurtado Chong. DISSERTATION: 27-abril-2010. ACADEMIC GRADE: Sobresaliente cum laude por unanimidad.
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TITLE: “Factores extracelulares y células madre neurales: Efectos de FGF-2, EGF, IGF-I y Neurotrofinas durante la neurogénesis y sinaptogénesis”. PhD STUDENT: Vanesa Nieto Estévez. DISSERTATION: 14-mayo-2013. ACADEMIC GRADE: Apto cum laude por unanimidad.
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TITLE: “Sudying the neurogenic potential of local progenitors in the adult olfactory bulb and their biocompatibility with graphene”. PhD STUDENT: Çagla Defterali. DISSERTATION: 3-julio-2015. ACADEMIC GRADE: Sobresaliente cum laude por unanimidad.
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TITLE: “Generation and differentiation of dopaminergic neurons from mouse multipotent and human induced pluripotent stem cells to study Parkinson´s disease”. PhD STUDENT: Eva Rodríguez Traver. DISSERTATION: 13-septiembre-2017. ACADEMIC GRADE: Sobresaliente cum laude.
Financing
- Ministerio de Ciencia e Innovación. Gobierno de España
- Consejo Superior de Investigaciones Científicas (CSIC)
- CIBERNED, CIBER, INSTITUTO DE SALUD CARLOS III (ISCIII)
- European Union
- Comunidad de Madrid
- Fundación Ramón Areces
Neuroscience Research Center dependent on the CSIC. Founded in 1920 and initially directed by Santiago Ramón y Cajal. World reference in the study of the brain. Custodian of the Cajal Legacy.
Activities