Epidermal growth factor (EGF) and fibroblast growth factor (FGF) are mitogens that promote<unk>  progenitor and stem<unk>  growth in vitro, though other factors synthesized by the<unk>  progenitor and stem<unk>  populations are also required for optimal growth. It is hypothesized that neurogenesis in the adult brain originates from<unk> s. The origin and identity of<unk> s in the adult brain remain to be defined. During differentiation The most widely accepted model of an adult<unk>  is a radial, glial fibrillary acidic protein-positive<unk> . Quiescent stem<unk> s are Type B that are able to remain in the quiescent state due to the renewable tissue provided by the specific niches composed of blood vessels, astrocytes, microglia, ependymal<unk> s, and extracellular matrix present within the brain. These niches provide nourishment, structural support, and protection for the stem<unk> s until they are activated by external stimuli. Once activated, the Type B<unk> s develop into Type C<unk> s, active proliferating intermediate<unk> s, which then divide into neuroblasts consisting of Type A<unk> s. The undifferentiated neuroblasts form chains that migrate and develop into mature neurons. In the olfactory bulb, they mature into GABAergic granule neurons, while in the hippocampus they mature into dentate granule<unk> s. Epigenetic modification Epigenetic modifications are important regulators of gene expression in differentiating<unk> s. Key epigenetic modifications include DNA cytosine methylation to form 5-methylcytosine and 5-methylcytosine demethylation. These types of modification are critical for<unk>  fate determination in the developing and adult mammalian brain. DNA cytosine methylation is catalyzed by DNA methyltransferases (DNMTs). Methylcytosine demethylation is catalyzed in several distinct steps by TET enzymes that carry out oxidative reactions (e.g. 5-methylcytosine to 5-hydroxymethylcytosine) and enzymes of the DNA base excision repair (BER) pathway. During disease<unk> s have an important role during development producing the enormous diversity of neurons, astrocytes and oligodendrocytes in the developing CNS. They also have important role in adult animals, for instance in learning and hippocampal plasticity in the adult mice in addition to supplying neurons to the olfactory bulb in mice. Notably the role of<unk> s during diseases is now being elucidated by several research groups around the world. The responses during stroke, multiple sclerosis, and Parkinson's disease in animal models and humans is part of the current investigation. The results of this ongoing investigation may have future applications to treat human<unk> ogical diseases.<unk> s have been shown to engage in migration and replacement of dying neurons in classical experiments performed by Sanjay Magavi and Jeffrey Macklis. Using a laser-induced damage of cortical layers, Magavi showed that SVZ<unk>  progenitors expressing Doublecortin, a critical molecule for migration of neuroblasts, migrated long distances to the area of damage and differentiated into mature neurons expressing NeuN marker. In addition, Masato Nakafuku's group from Japan showed for the first time the role of hippocampal stem<unk> s during stroke in mice. These results demonstrated that<unk> s can engage in the adult brain as a result of injury. Furthermore, in 2004 Evan Y. Snyder's group showed that<unk> s migrate to brain tumors in a directed fashion. Jaime Imitola, M.D and colleagues from Harvard demonstrated for the first time, a molecular mechanism for the responses of<unk> s to injury. They showed that chemokines released during injury such as SDF-1a were responsible for the directed migration of human and mouse<unk> s to areas of injury in mice. Since then other molecules have been found to participate in the responses of<unk> s to injury. All these results have been widely reproduced and expanded by other investigators joining the classical work of Richard L. Sidman in autoradiography to visualize neurogenesis during development, and neurogenesis in the adult by Joseph Altman in the 1960s, as evidence of the responses of adult<unk> s activities and neurogenesis during homeostasis and injury. The search for additional mechanisms that operate in the injury environment and how they influence the responses of<unk> s during acute and chronic disease is matter of intense research.
Neural stem cell
Stem cell
Progenitor cell
Hematopoietic stem cell
Hemangioblast
Trophoblast
Neuroblast
Cancer-associated fibroblast