Promoting brain regeneration through cellular reprogramming

P Rodríguez-Cumbreras(2,3,4,5) F Cala(2,4,5) F M Vega(2,3,4,5) B Berninger(1) R Pardal(2,3,4,5) A Platero-Luengo(2,3,4,5)

1:King's College London; 2:Instituto de Biomedicina de Sevilla (IBiS); 3:Universidad de Sevilla; 4:Hospital Universitario Virgen del Rocío (HUVR); 5:Consejo Superior de Investigaciones Científicas (CSIC)

Although our knowledge about brain physiology has expanded significantly, most neurological conditions remain uncured. The mammalian brain has very limited regenerative capacity, since most of its cells are not replaced during normal or pathological situations. Neurons and their connections are established early in life and are designed to age with the individual.

In the lab we take advantage of the reprogramming technology to address regeneration. Nuclear cell reprogramming has emerged as a method that allows the age and identity of virtually any cell to be reversed to an embryonic-like stage by the action of the 4 Yamanaka Factors (4F). It has been shown that partial reprogramming (PR), the transient expression of the 4F, is sufficient to generate intermediate progenitors in some tissues, in addition to lead the cells to a youthful state. We use PR specifically in astroglia to revert these cells to a progenitor state with the aim of generating neural stem cell-like cells with the capacity to differentiate into induced neurons. Also, we propose to rejuvenate astroglia by PR in order to reduce age-related neuroinflammation to promote brain homeostasis and the maintenance of a healthy neuronal population.