Neural stem cells NSCs are present not only during the embryonic development but also in the adult brain of all mammalian species, including humans. Stem cell niche architecture in vivo enables adult NSCs to continuously generate functional neurons in specific brain regions throughout life. The adult neurogenesis process is subject to dynamic regulation by various physiological, pathological and pharmacological stimuli. Multipotent adult NSCs also appear to be intrinsically plastic, amenable to genetic programming during normal differentiation, and to epigenetic reprogramming during de-differentiation into pluripotency. Increasing evidence suggests that adult NSCs significantly contribute to specialized neural functions under physiological and pathological conditions. Fully understanding the biology of adult NSCs will provide crucial insights into both the etiology and potential therapeutic interventions of major brain disorders. Here we review recent progress on adult NSCs of the mammalian central nervous system, including topics on their identity, niche, function, plasticity, and emerging roles in cancer and regenerative medicine. The discovery of adult mammalian neural stem cells NSCs marks a milestone in the odyssey of our contemporary understanding of adult brain plasticity. Early in the twentieth century, influential histological and anatomic studies of Koelliker, His, Bizzozero and Cajal had established that the adult mammalian brain remained structurally constant after birth and no new neurons could be conceivably generated in adulthood [ 1 — 3 ]. In the adult centers, the nerve paths are something fixed, ended, and immutable.
Mini Review ARTICLE
Over many decades, constructing genetically and phenotypically stable lines of neural stem cells NSC for clinical purposes with the aim of restoring irreversibly lost functions of nervous tissue has been one of the major goals for multiple research groups. The unique ability of stem cells to maintain their own pluripotent state even in the adult body has made them into the choice object of study. With the development of the technology for induced pluripotent stem cells iPSCs and direct transdifferentiation of somatic cells into the desired cell type, the initial research approaches based on the use of allogeneic NSCs from embryonic or fetal nervous tissue are gradually becoming a thing of the past. The focus is on performing direct reprogramming while bypassing the stage of iPSCs which is known for genetic instability and an increased risk of tumorigenesis. A detailed description of various protocols for obtaining reprogrammed neural cells used in the therapy of the nervous system pathology is also provided. Initially, the technology of restoring pluripotency in differentiated cells was developed in by R. Briggs and T. King who used the method of nuclear transplantation [ 1 ].
Stem Cells International
Adult somatic stem cells in various organs maintain homeostatic tissue regeneration and enhance plasticity. Since its initial discovery five decades ago, investigations of adult neurogenesis and neural stem cells have led to an established and expanding field that has significantly influenced many facets of neuroscience, developmental biology and regenerative medicine. Here we review recent progress and focus on questions related to adult mammalian neural stem cells that also apply to other somatic stem cells. We further discuss emerging topics that are guiding the field toward better understanding adult neural stem cells and ultimately applying these principles to improve human health. Joseph Altman first suggested that neurogenesis, or the generation of new neurons, occurs beyond development in the adult mammalian brain Altman and Das, His findings sparked optimism that this endogenous process can be harnessed to repair the injured or diseased brain. Significant progress in the investigation of this phenomenon has since led to remarkable knowledge about adult NSCs and neurogenesis Ming and Song, For example, pioneering in vitro analysis demonstrated self-renewal and multipotency of NSCs derived from the adult mammalian brain Reynolds and Weiss, In vivo studies using nucleotide analog labeling, retroviral lineage-tracing and genetic fate-mapping later revealed NSC population dynamics, differentiation capacities, regulatory mechanisms and heterogeneity. Single-cell genetic lineage-tracing has illustrated the existence of endogenous adult mammalian NSCs with hallmark stem cell properties Bonaguidi et al.
The generation of new neurons is a lifelong process in many vertebrate species that provides an extra level of plasticity to several brain circuits. Frequently, neurogenesis in the adult brain is considered a continuation of earlier developmental processes as it relies in the persistence of neural stem cells, similar to radial glia, known as radial glia-like cells RGLs. However, adult RGLs are not just leftovers of progenitors that remain in hidden niches in the brain after development has finished. Rather, they seem to be specified and set aside at specific times and places during embryonic and postnatal development. The adult RGLs present several cellular and molecular properties that differ from those observed in developmental radial glial cells such as an extended cell cycle length, acquisition of a quiescence state, a more restricted multipotency and distinct transcriptomic programs underlying those cellular processes.