Adult neural stem cells: intrinsic and extrinsic factors that regulate their self-renewal and differentiation

Research summary:

The principal investigator (Dr. Eva Porlan) is a beneficiary of the Ramón y Cajal program, and has established a novel and independent line of research in the CBMSO, since 2016. This line focuses on the study of intrinsic and extrinsic factors that regulate the quiescence-proliferation switch and the mode of division of mammalian adult neural stem cells (NSC), and how these factors contribute to the maintenance of NSCs in their natural dwelling reservoirs, the neurogenic niches. The subependymal zone (also known as the subventricular zone) is the most prolific neurogenic niche in adult rodents, where residing stem cells generate large numbers of immature neurons that migrate into the olfactory bulb, where they differentiate into different types of interneurons. In a society of demographic change like is our own, a research challenge is the search for druggable targets to mobilize NSCs at their endogenous niches in order to activate stem cells that are mainly quiescent to divide and generate differentiated and functional progeny. This strategy holds promise to promote regenerative responses in physiological ageing, brain lesions or similar pathological situations, and appears as a very attractive venue for the future of cell replacement therapies. We are currently exploring the potential of targets whose biological activity are susceptible of pharmacological modulation for enhancing NSC transition into proliferation and neurogenic output, both during homeostasis and in damage-regeneration paradigms in the adult brain.

Image

A representative confocal microphotograph of murine neural stem cells at the subependymal niche. Shown are ependymal cells (big polygonal cells, outlined by membrane beta-catenin staining –blue-, displaying multiple motile cilia, revealed by gamma-tubulin staining –red-. Neural stem cells are stained with the glial marker GFAP –green-, and univocally identified by the simultaneous immunoreactivity for gamma-tubulin to show one unique basal body revealing the presence of a primary cilium –red-. The combined structure of the ependymal cell wall and the stem cells at their center has been termed ‘pinwheel’.

Image


* For external calls please dial 34 91196 followed by the extension number
Last nameNameLaboratoryExt.*e-mailProfessional category
Barrios MuñozAna Laura3064630ana.barrios(at)cbm.csic.esTit.Sup.Activ.Técn.y Profes. GP1
López FonsecaCoral3064655coral.lopez(at)cbm.csic.esTitulado Sup.de Actividades Técn. y Profes. GP1
Porlan AlonsoEva3064655eva.porlan(at)cbm.csic.esInvestigador

Relevant publications:

  • Morante-Redolat, J.M., and Porlan, E. (2019). Neural Stem Cell Regulation by Adhesion Molecules Within the Subependymal Niche. Front Cell Dev Biol 7, 102.
  • Piniella, D., Martinez-Blanco, E., Ibanez, I., Bartolome-Martin, D., Porlan, E., Diez-Guerra, J., Gimenez, C., and Zafra, F. (2018). Identification of novel regulatory partners of the glutamate transporter GLT-1. Glia 66, 2737-2755.
  • Porlan, E., Marti-Prado, B., Consiglio, A., and Farinas, I. (2016). Stable and Efficient Genetic Modification of Cells in the Adult Mouse V-SVZ for the Analysis of Neural Stem Cell Autonomous and Non-autonomous Effects. J Vis Exp, 53282.
  • Quereda, V., Porlan, E., Canamero, M., Dubus, P., and Malumbres, M. (2016). An essential role for Ink4 and Cip/Kip cell-cycle inhibitors in preventing replicative stress. Cell Death Differ 23, 430-441.
  • Porlan, E., Marti-Prado, B., Morante-Redolat, J.M., Consiglio, A., Delgado, A.C., Kypta, R., Lopez-Otin, C., Kirstein, M., and Farinas, I. (2014). MT5-MMP regulates adult neural stem cell functional quiescence through the cleavage of N-cadherin. Nat Cell Biol 16, 629-638.
  • Delgado, A.C., Ferron, S.R., Vicente, D., Porlan, E., Perez-Villalba, A., Trujillo, C.M., D'Ocon, P., and Farinas, I. (2014). Endothelial NT-3 delivered by vasculature and CSF promotes quiescence of subependymal neural stem cells through nitric oxide induction. Neuron 83, 572-585.
  • Marques-Torrejon, M.A., Porlan, E., Banito, A., Gomez-Ibarlucea, E., Lopez-Contreras, A.J., Fernandez-Capetillo, O., Vidal, A., Gil, J., Torres, J., and Farinas, I. (2013). Cyclin-dependent kinase inhibitor p21 controls adult neural stem cell expansion by regulating Sox2 gene expression. Cell Stem Cell 12, 88-100.
  • Porlan, E., Morante-Redolat, J.M., Marques-Torrejon, M.A., Andreu-Agullo, C., Carneiro, C., Gomez-Ibarlucea, E., Soto, A., Vidal, A., Ferron, S.R., and Farinas, I. (2013). Transcriptional repression of Bmp2 by p21(Waf1/Cip1) links quiescence to neural stem cell maintenance. Nature neuroscience 16, 1567-1575.
  • Porlan, E., Perez-Villalba, A., Delgado, A.C., and Ferron, S.R. (2013). Paracrine regulation of neural stem cells in the subependymal zone. Arch Biochem Biophys 534, 11-19.

Doctoral theses:

  • Beatriz Martí Prado. Estudio de la quiescencia y activación de las células madre neurales adultas por uniones adherentes: papel de la N-cadherina”. Directores: Eva Porlan e Isabel Fariñas. Facultad de Ciencias Biológicas, Departamento de Biología Celular, Biología Funcional y Antropología Física de la Universidad de Valencia. 19/07/2017

NOTE! This site uses cookies and similar technologies.

If you not change browser settings, you agree to it. Learn more

I understand

COOKIES POLICY

What are cookies?

A cookie is a file that is downloaded to your computer when you access certain web pages. Cookies allow a web page, among other things, to store and retrieve information about the browsing habits of a user or their equipment and, depending on the information they contain and the way they use their equipment, they can be used to recognize the user.

Types of cookies

Classification of cookies is made according to a series of categories. However, it is necessary to take into account that the same cookie can be included in more than one category.

  1. Cookies according to the entity that manages them

    Depending on the entity that manages the computer or domain from which the cookies are sent and treat the data obtained, we can distinguish:

    • Own cookies: those that are sent to the user's terminal equipment from a computer or domain managed by the editor itself and from which the service requested by the user is provided.
    • Third party cookies: those that are sent to the user's terminal equipment from a computer or domain that is not managed by the publisher, but by another entity that processes the data obtained through the cookies. When cookies are installed from a computer or domain managed by the publisher itself, but the information collected through them is managed by a third party, they cannot be considered as own cookies.

  2. Cookies according to the period of time they remain activated

    Depending on the length of time that they remain activated in the terminal equipment, we can distinguish:

    • Session cookies: type of cookies designed to collect and store data while the user accesses a web page. They are usually used to store information that only is kept to provide the service requested by the user on a single occasion (e.g. a list of products purchased).
    • Persistent cookies: type of cookies in which the data is still stored in the terminal and can be accessed and processed during a period defined by the person responsible for the cookie, which can range from a few minutes to several years.

  3. Cookies according to their purpose

    Depending on the purpose for which the data obtained through cookies are processed, we can distinguish between:

    • Technical cookies: those that allow the user to navigate through a web page, platform or application and the use of different options or services that exist in it, such as controlling traffic and data communication, identifying the session, access to restricted access parts, remember the elements that make up an order, perform the purchase process of an order, make a registration or participation in an event, use security elements during navigation, store content for the broadcast videos or sound or share content through social networks.
    • Personalization cookies: those that allow the user to access the service with some predefined general characteristics based on a series of criteria in the user's terminal, such as the language, the type of browser through which the user accesses the service, the regional configuration from where you access the service, etc.
    • Analytical cookies: those that allow the person responsible for them to monitor and analyse the behaviour of the users of the websites to which they are linked. The information collected through this type of cookies is used in the measurement of the activity of the websites, applications or platforms, and for the elaboration of navigation profiles of the users of said sites, applications and platforms, in order to introduce improvements in the analysis of the data of use made by the users of the service.

Cookies used on our website

The CBMSO website uses Google Analytics. Google Analytics is a simple and easy to use tool that helps website owners to measure how users interact with the content of the site. You can consult more information about the cookies used by Google Analitycs in this link.

Acceptance of the Cookies Policy

The CBMSO assumes that you accept the use of cookies if you continue browsing, considering that it is a conscious and positive action from which the user's consent is inferred. In this regard, you are previously informed that such behaviour will be interpreted that you accept the installation and use of cookies.

Knowing this information, it is possible to carry out the following actions:

  • Accept cookies: if the user presses the acceptance button, this warning will not be displayed again when accessing any page of the portal.
  • Review the cookies policy: the user can access to this page in which the use of cookies is detailed, as well as links to modify the browser settings.

How to modify the configuration of cookies

Using your browser you can restrict, block or delete cookies from any web page. In each browser the process is different, here we show you links on this particular of the most used browsers: