8/23/2023 0 Comments Adult neural stem cells![]() ![]() Identification of regulatory networks in HSCs and their immediate progeny via integrated proteome, transcriptome, and DNA methylome. Dynamic axonal translation in developing and mature visual circuits. RiboTag analysis of actively translated mRNAs in Sertoli and Leydig cells in vivo. Cell-type-specific isolation of ribosome-associated mRNA from complex tissues. Imaging protein synthesis in cells and tissues with an alkyne analog of puromycin. Prospective identification of functionally distinct stem cells and neurosphere-initiating cells in adult mouse forebrain. Prospective identification and purification of quiescent adult neural stem cells from their in vivo niche. In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics. Haematopoietic stem cells require a highly regulated protein synthesis rate. Stem cell function and stress response are controlled by protein synthesis. Slowly dividing neural progenitors are an embryonic origin of adult neural stem cells. embryonic origin of postnatal neural stem cells. Single-cell transcriptomics reveals a population of dormant neural stem cells that become activated upon brain injury. Our results reveal a control mechanism by which the cell cycle is coupled to post-transcriptional repression of key stem cell identity factors, thereby promoting exit from stemness. The decrease of mTORC1 activity as stem cells exit the cell cycle selectively blocks translation of these transcripts. The generation of neurogenic progeny involves translational repression of a subset of mRNAs, including mRNAs that encode the stem cell identity factors SOX2 and PAX6, and components of the translation machinery, which are enriched in a pyrimidine-rich motif. Examination of individual transcripts using RiboTag mouse models reveals that whereas stem cells translate abundant transcripts with little discrimination, translation becomes increasingly regulated with the onset of differentiation. Here we show that protein synthesis undergoes highly dynamic changes when stem cells differentiate to neurons in vivo. However, when post-transcriptional regulation is acquired and how protein synthesis changes along the different steps of maturation are not known. This uncoupling of general availability of mRNA from translation into protein facilitates immediate responses to environmental changes and avoids excess production of proteins, which is the most energy-consuming process within the cell. Neurons also maintain a subset of messenger RNAs in a translationally silent state, which react ‘on demand’ to intracellular and extracellular signals. Quiescent stem cells exhibit a low level of protein synthesis 1, which is key to maintaining the pool of fully functional stem cells, not only in the brain but also in the bone marrow and hair follicles 2, 3, 4, 5, 6. Whether post-transcriptional regulation of gene expression controls differentiation of stem cells for tissue renewal remains unknown.
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