title: Mouse embryonic stem cell-derived cells reveal niches that support neuronal differentiation in the adult rat brain.
abstract: A neurogenic niche can be identified by the proliferation and differentiation of its naturally residing neural stem cells. However, it remains unclear whether "silent" neurogenic niches or regions suitable for neural differentiation, other than the areas of active neurogenesis, exist in the adult brain. Embryoid body (EB) cells derived from embryonic stem cells (ESCs) are endowed with a high potential to respond to specification and neuralization signals of the embryo. Hence, to identify microenvironments in the postnatal and adult rat brain with the capacity to support neuronal differentiation, we transplanted dissociated EB cells to conventional neurogenic and non-neurogenic regions. Our results show a neuronal differentiation pattern of EB cells that was dependent on the host region. Efficient neuronal differentiation of EB cells occurred within an adjacent region to the rostral migratory stream. EB cell differentiation was initially patchy and progressed toward an even distribution along the graft by 15-21 days post-transplantation, giving rise mostly to GABAergic neurons. EB cells in the striatum displayed a lower level of neuronal differentiation and derived into a significant number of astrocytes. Remarkably, when EB cells were transplanted to the striatum of adult rats after a local ischemic stroke, increased number of neuroblasts and neurons were observed. Unexpectedly, we determined that the adult substantia nigra pars compacta, considered a non-neurogenic area, harbors a robust neurogenic environment. Therefore, neurally uncommitted cells derived from ESCs can detect regions that support neuronal differentiation within the adult brain, a fundamental step for the development of stem cell-based replacement therapies.
authors.affiliation: Department of Molecular Neuropathology, Instituto de Fisiología Celular.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Maya-Espinosa
authors.forename: Omar
authors.initials: O
authors.lastname: Collazo-Navarrete
authors.forename: Diana
authors.initials: D
authors.lastname: Millán-Aldaco
authors.forename: Marcela
authors.initials: M
authors.lastname: Palomero-Rivero
authors.forename: Gilda
authors.initials: G
authors.lastname: Guerrero-Flores
authors.forename: René
authors.initials: R
authors.lastname: Drucker-Colín
authors.forename: Luis
authors.initials: L
authors.lastname: Covarrubias
authors.forename: Magdalena
authors.initials: M
authors.lastname: Guerra-Crespo
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation; D002460:Cell Line; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D053595:Embryonic Stem Cells / Q000378:metabolism* / Q000473:pathology; D059330:GABAergic Neurons / Q000378:metabolism* / Q000473:pathology; D064593:Heterografts; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D055153:Stem Cell Niche; D033581:Stem Cell Transplantation; D020521:Stroke / Q000378:metabolism / Q000473:pathology / Q000628:therapy
keywords: Embryonic stem cells; Neural differentiation; Neural stem cell; Stem cell transplantation