Phosphoserine phosphatase is expressed in the neural stem cell niche and regulates neural stem and progenitor cell proliferation.
ABSTRACT Phosphoserine phosphatase (PSP) metabolizes the conversion of l-phosphoserine to l-serine, classically known as an amino acid necessary for protein and nucleotide synthesis and more recently suggested to be involved in cell-to-cell signaling. Previously, we identified PSP as being enriched in proliferating neural progenitors and highly expressed by embryonic and hematopoietic stem cells, suggesting a general role in stem cells. Here we demonstrate that PSP is highly expressed in periventricular neural progenitors in the embryonic brain. In the adult brain, PSP expression was observed in slowly dividing or quiescent glial fibrillary acidic protein (GFAP)-positive cells and CD24-positive ependymal cells in the forebrain germinal zone adjacent to the lateral ventricle and within GFAP-positive cells of the hippocampal subgranular zone, consistent with expression in adult neural stem cells. In vitro, PSP overexpression promoted proliferation, whereas small interfering RNA-induced knockdown inhibited proliferation of neural stem cells derived from embryonic cortex and adult striatal subventricular zone. The effects of PSP knockdown were partially rescued by exogenous l-serine. These data support a role for PSP in neural stem cell proliferation and suggest that in the adult periventricular germinal zones, PSP may regulate signaling between neural stem cells and other cells within the stem cell niche. Disclosure of potential conflicts of interest is found at the end of this article.
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ABSTRACT: Neural stem cells (NSCs) in the adult brain have been a consistent focus of biomedical research largely because of their potential clinical application. To fully exploit this potential, the molecular mechanisms that regulate NSCs must be clarified. Several lines of evidence show that a multifunctional protein, Galectin-1, is expressed and has a functional role in a subset of adult NSCs. Researchers, including our group, have explored the physiological role of Galectin-1 in NSCs and its application in the treatment of animal models of neurological disorders such as brain ischemia and spinal cord injury. Here, we summarize what is currently known regarding the role of Galectin-1 in adult NSCs. Furthermore, we discuss current issues in researching the role of Galectin-1 in adult NSCs under both physiological and pathological conditions.Developmental Neurobiology 04/2012; 72(7):1059-67. · 4.42 Impact Factor
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ABSTRACT: The recent convergence of pathology, cancer research and basic neurobiology disciplines is providing unprecedented insights to the origins of brain tumours. This new knowledge holds great promise for patients, transforming the way we view and develop new treatments for these devastating diseases.Neuropathology and Applied Neurobiology 06/2012; 38(3):222-7. · 4.84 Impact Factor
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ABSTRACT: The metabolic enzyme for folate, Aldh1L1, has been shown to be expressed robustly in astrocytes of the brain. It is now well accepted that astrocytes in certain regions of the adult brain also serve as neural stem cells. Here, we examined whether Aldh1L1 is also expressed in postnatal neural stem cells. In vitro, cells in neural stem cell culture conditions have robust Aldh1L1 promoter activity. In vivo, in the adult brain, astroctyes in neurogenic regions express Aldh1L1 in a pattern consistent with inclusion in neural stem cells, and analysis of Aldh1L1+ cell transcriptome profiles from neurogenic regions reveal a robust enrichment of known regulators of neurogenesis. Genetic fate mapping with Aldh1L1 BAC Cre animals reveals adult-born neuroblasts of the rostral migratory stream are derived from Aldh1L1 expressing cells, as are sporadic neurons in other regions of the brain. Combining these lines of evidence from transgenic animals, cell culture, transcriptome profiling, and fate mapping, we conclude that Aldh1L1 is also expressed in neural stem cells in the brain. These findings may influence the future design of experiments utilizing Aldh1L1 genetic tools, and also suggest existing Aldh1L1 bacTRAP mice may be of use for further experiments profiling neural stem cells in vivo. GLIA 2013;Glia 07/2013; · 5.07 Impact Factor