Novel C1q receptor-mediated signaling controls neural stem cell behavior and neurorepair

C1q plays a key role as a recognition molecule in the immune system, driving autocatalytic complement cascade activation and acting as an opsonin. We have previously reported a non-immune role of complement C1q modulating the migration and fate of human neural stem cells (hNSC); however, the mechanism underlying these effects has not yet been identified. Here, we show for the first time that C1q acts as a functional hNSC ligand, inducing intracellular signaling to control cell behavior. Using an unbiased screening strategy, we identified five transmembrane C1q signaling/receptor candidates in hNSC (CD44, GPR62, BAI1, c-MET, and ADCY5). We further investigated the interaction between C1q and CD44 , demonstrating that CD44 mediates C1q induced hNSC signaling and chemotaxis in vitro, and hNSC migration and functional repair in vivo after spinal cord injury. These results reveal a receptor-mediated mechanism for C1q modulation of NSC behavior and show that modification of C1q receptor expression can expand the therapeutic window for hNSC transplantation.
Source: eLife - Category: Biomedical Science Tags: Stem Cells and Regenerative Medicine Source Type: research

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Injuries to the central nervous system (CNS) are inefficiently repaired. Resident neural stem cells manifest a limited contribution to cell replacement. We have uncovered a latent potential in neural stem cells to replace large numbers of lost oligodendrocytes in the injured mouse spinal cord. Integrating multimodal single-cell analysis, we found that neural stem cells are in a permissive chromatin state that enables the unfolding of a normally latent gene expression program for oligodendrogenesis after injury. Ectopic expression of the transcription factor OLIG2 unveiled abundant stem cell–derived oligodendrogenesis...
Source: ScienceNOW - Category: Science Authors: Tags: Development, Neuroscience, Online Only r-articles Source Type: news
In conclusion, using a large cohort with rich health and DNA methylation data, we provide the first comparison of six major epigenetic measures of biological ageing with respect to their associations with leading causes of mortality and disease burden. DNAm GrimAge outperformed the other measures in its associations with disease data and associated clinical traits. This may suggest that predicting mortality, rather than age or homeostatic characteristics, may be more informative for common disease prediction. Thus, proteomic-based methods (as utilised by DNAm GrimAge) using large, physiologically diverse protein sets for p...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract The mammalian central nervous system (CNS) has a limited ability to renew the damaged cells after a brain or spinal cord injury whether it is nonhuman primates like monkeys or humans. Transplantation of neural stem cells (NSCs) is a potential therapy for CNS injuries due to their pluripotency and differentiation abilities. Cytokines play an important role in CNS development and repair of CNS injuries. However, the detailed cytokine signaling response in monkey neural stem cells is rarely studied. In our previous research, we isolated NSCs from the adult monkey brain and found the effects of cytokines on m...
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
Bone marrow mesenchymal stem cells improve spinal function of spinal cord injury in rats via TGF-β/Smads signaling pathway. Exp Ther Med. 2020 Jun;19(6):3657-3663 Authors: Lv C, Zhang T, Li K, Gao K Abstract Bone marrow mesenchymal stem cells (BMSCs) on the repair of spinal cord injury (SCI) in rats as well as the role of transforming growth factor-β (TGF-β)/Smads signaling pathway in the repair were investigated. Rat BMSCs and astrocyte-spinal cords (ASCs) were isolated and cultured in vitro, and the cell purity was detected by flow cytometry. ASCs were co-cultured with TGF-β1, BMS...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
CONCLUSION: Activation of the PI3K/AKT pathway decreases the concentration of apoptotic factors, while the HIF pathway protects stem cells against the micro-environment of tissue (hypoxia). PMID: 32297579 [PubMed - as supplied by publisher]
Source: Current Pharmaceutical Biotechnology - Category: Biotechnology Authors: Tags: Curr Pharm Biotechnol Source Type: research
In this study, we induced neuronal differentiation of BMSCs in the presence of PD, and analysed the Nrf2 signalling and neuronal differentiation markers using routine molecular assays. We also established an in vivo model of SCI and assessed the locomotor function of the mice through hindlimb movements and electrophysiological measurements. Finally, tissue regeneration was evaluated by H&E staining, Nissl staining and transmission electron microscopy. PD (30 μmol/L) markedly facilitated BMSC differentiation into neuron-like cells by activating the Nrf2 pathway and increased the expression of neuronal markers i...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
We report a new class of natural-product-inspired covalent inhibitors of telomerase that target the catalytic active site. Age-Related Epigenetic Changes that Suppress Mitochondrial Function https://www.fightaging.org/archives/2020/03/age-related-epigenetic-changes-that-suppress-mitochondrial-function/ Today's open access research reports on two specific epigenetic changes observed in old individuals that act to reduce mitochondrial function. This joins an existing list of genes for which expression changes are known to impact mitochondrial function with age. A herd of hundreds of mitochondria are found ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Monosynaptic rabies tracing can be used to map inputs to stem cell ‐derived neurons grafted to models of neurodegenerative disease and injury. These studies indicate that graft neurons receive anatomically‐appropriate inputs, but it remains to be determined whether those inputs are necessary for functional recovery. Next‐generation rabies tracing is poised to address this outstanding question, which may aid ongoing translational efforts. ABSTRACTFetal neural progenitor grafts have been evaluated in preclinical animal models of spinal cord injury and Parkinson's disease for decades, but the initial reliance on primary...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Translational and Clinical Research Source Type: research
In conclusion, taller body height at the entry to adulthood, supposed to be a marker of early-life environment, is associated with lower risk of dementia diagnosis later in life. The association persisted when adjusted for educational level and intelligence test scores in young adulthood, suggesting that height is not just acting as an indicator of cognitive reserve. A Comparison of Biological Age Measurement Approaches https://www.fightaging.org/archives/2020/02/a-comparison-of-biological-age-measurement-approaches/ Researchers here assess the performance of a range of approaches to measuring biological...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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