Browsing by Subject "Ependymal cells"

Now showing 1 - 4 of 4
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    In vivo reprogramming of NG2 glia enables adult neurogenesis and functional recovery following spinal cord injury
    (Cell Press, 2021) Tai, Wenjiao; Wu, Wei; Wang, Lei-Lei; Ni, Haoqi; Chen, Chunhai; Yang, Jianjing; Zang, Tong; Zou, Yuhua; Xu, Xiao-Ming; Zhang, Chun-Li; Neurological Surgery, School of Medicine
    Adult neurogenesis plays critical roles in maintaining brain homeostasis and responding to neurogenic insults. However, the adult mammalian spinal cord lacks an intrinsic capacity for neurogenesis. Here we show that spinal cord injury (SCI) unveils a latent neurogenic potential of NG2+ glial cells, which can be exploited to produce new neurons and promote functional recovery after SCI. Although endogenous SOX2 is required for SCI-induced transient reprogramming, ectopic SOX2 expression is necessary and sufficient to unleash the full neurogenic potential of NG2 glia. Ectopic SOX2-induced neurogenesis proceeds through an expandable ASCL1+ progenitor stage and generates excitatory and inhibitory propriospinal neurons, which make synaptic connections with ascending and descending spinal pathways. Importantly, SOX2-mediated reprogramming of NG2 glia reduces glial scarring and promotes functional recovery after SCI. These results reveal a latent neurogenic potential of somatic glial cells, which can be leveraged for regenerative medicine.
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    Meningeal Fibrosis in the Axolotl Spinal Cord: Extracellular Matrix and Cellular Responses
    (2024-05) Sarria, Deborah A.; Chernoff, Ellen; Belecky-Adams, Teri; Blazer-Yost, Bonnie; Cummins, Theodore; Dai, Guoli
    Though mammalian spinal cord injury (SCI) has long been a topic of study, effective therapies that promote functional recovery are not yet available. The axolotl, Ambystoma mexicanum, is a valuable animal model in the investigation of spinal cord regeneration, as this urodele is able to achieve functional recovery even after complete spinal cord transection. Understanding the similarities and differences between the mammalian SCI response and that of the axolotl provides insight into the process of successful regeneration, and bolsters the fundamental knowledge used in the development of future mammalian SCI treatments. This thesis provides a detailed analysis of the ultrastructure of the axolotl meninges, as this has not yet been presented in existing literature, and reveals that the axolotl meninges consist of 3 distinct layers as does mammalian meninges; the dura mater, arachnoid mater, and pia mater. The role of reactive meningeal and ependymal cells is also investigated in regard to the deposition and remodeling of the fibrotic ECM, which is found to be similar in composition to hydrogel scaffolds being studied in mammalian SCI. It is shown that meningeal fibroblasts are the primary source of the extensive fibrillar collagen deposition that fills the entire spinal canal, peaking at approximately 3 weeks post transection and remaining until approximately 5 weeks post transection, and that there is no deposition of type IV collagen within the lesion site. Mesenchymal ependymal cells are shown to contribute to the ECM deposition through the production of glycosaminoglycans that are used in sidechains of both unsulfated and sulfated proteoglycans, while simultaneously remodeling the ECM through the production of MMPs and phagocytosis of cellular debris. Further, this study shows that mesenchymal ependymal cells and a population of foamy macrophages contribute to the degradation of the fibrin clot that forms in the acute phase of injury, and that this fibrin clot provides a necessary and permissive substrate for early mesenchymal outgrowth.
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    Meningeal Foam Cells and Ependymal Cells in Axolotl Spinal Cord Regeneration
    (Frontiers, 2019-11) Enos, Nathaniel; Takenaka, Hidehito; Scott, Sarah; Salfity, Hai V. N.; Kirk, Maia; Egar, Margaret W.; Sarria, Deborah A.; Slayback-Barry, Denise; Belecky-Adams, Teri; Chernoff, Ellen A. G.; Biology, School of Science
    A previously unreported population of foam cells (foamy macrophages) accumulates in the invasive fibrotic meninges during gap regeneration of transected adult Axolotl spinal cord (salamander Ambystoma mexicanum) and may act beneficially. Multinucleated giant cells (MNGCs) also occurred in the fibrotic meninges. Actin-label localization and transmission electron microscopy showed characteristic foam cell and MNGC podosome and ruffled border-containing sealing ring structures involved in substratum attachment, with characteristic intermediate filament accumulations surrounding nuclei. These cells co-localized with regenerating cord ependymal cell (ependymoglial) outgrowth. Phase contrast-bright droplets labeled with Oil Red O, DiI, and DyRect polar lipid live cell label showed accumulated foamy macrophages to be heavily lipid-laden, while reactive ependymoglia contained smaller lipid droplets. Both cell types contained both neutral and polar lipids in lipid droplets. Foamy macrophages and ependymoglia expressed the lipid scavenger receptor CD36 (fatty acid translocase) and the co-transporter toll-like receptor-4 (TLR4). Competitive inhibitor treatment using the modified fatty acid Sulfo-N-succinimidyl Oleate verified the role of the lipid scavenger receptor CD36 in lipid uptake studies in vitro. Fluoromyelin staining showed both cell types took up myelin fragments in situ during the regeneration process. Foam cells took up DiI-Ox-LDL and DiI-myelin fragments in vitro while ependymoglia took up only DiI-myelin in vitro. Both cell types expressed the cysteine proteinase cathepsin K, with foam cells sequestering cathepsin K within the sealing ring adjacent to the culture substratum. The two cell types act as sinks for Ox-LDL and myelin fragments within the lesion site, with foamy macrophages showing more Ox-LDL uptake activity. Cathepsin K activity and cellular localization suggested that foamy macrophages digest ECM within reactive meninges, while ependymal cells act from within the spinal cord tissue during outgrowth into the lesion site, acting in complementary fashion. Small MNGCs also expressed lipid transporters and showed cathepsin K activity. Comparison of 3H-glucosamine uptake in ependymal cells and foam cells showed that only ependymal cells produce glycosaminoglycan and proteoglycan-containing ECM, while the cathepsin studies showed both cell types remove ECM. Interaction of foam cells and ependymoglia in vitro supported the dispersion of ependymal outgrowth associated with tissue reconstruction in Axolotl spinal cord regeneration.
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    TMEM106B amyloid filaments in the Biondi bodies of ependymal cells
    (Springer, 2024-11-06) Ghetti, Bernardino; Schweighauser, Manuel; Jacobsen, Max H.; Gray, Derrick; Bacioglu, Mehtap; Murzin, Alexey G.; Glazier, Bradley S.; Katsinelos, Taxiarchis; Vidal, Ruben; Newell, Kathy L.; Gao, Sujuan; Garringer, Holly J.; Spillantini, Maria Grazia; Scheres, Sjors H. W.; Goedert, Michel; Pathology and Laboratory Medicine, School of Medicine
    Biondi bodies are filamentous amyloid inclusions of unknown composition in ependymal cells of the choroid plexuses, ependymal cells lining cerebral ventricles and ependymal cells of the central canal of the spinal cord. Their formation is age-dependent and they are commonly associated with a variety of neurodegenerative conditions, including Alzheimer's disease and Lewy body disorders. Here, we show that Biondi bodies are strongly immunoreactive with TMEM239, an antibody specific for inclusions of transmembrane protein 106B (TMEM106B). Biondi bodies were labelled by both this antibody and the amyloid dye pFTAA. Many Biondi bodies were also labelled for TMEM106B and the lysosomal markers Hexosaminidase A and Cathepsin D. By transmission immuno-electron microscopy, Biondi bodies of choroid plexuses were decorated by TMEM239 and were associated with structures that resembled residual bodies or secondary lysosomes. By electron cryo-microscopy, TMEM106B filaments from Biondi bodies of choroid plexuses were similar (Biondi variant), but not identical, to the fold I that was previously identified in filaments from brain parenchyma.