by Keyword: neurotrophic factor
Smith, CS, Alvarez, Z, Qiu, RM, Sasselli, IR, Clemons, T, Ortega, JA, Vilela-Picos, M, Wellman, H, Kiskinis, E, Stupp, SI, (2023). Enhanced Neuron Growth and Electrical Activity by a Supramolecular Netrin-1 Mimetic Nanofiber Acs Nano 17, 19887-19902
Neurotrophic factors are essential not only for guiding the organization of the developing nervous system but also for supporting the survival and growth of neurons after traumatic injury. In the central nervous system (CNS), inhibitory factors and the formation of a glial scar after injury hinder the functional recovery of neurons, requiring exogenous therapies to promote regeneration. Netrin-1, a neurotrophic factor, can initiate axon guidance, outgrowth, and branching, as well as synaptogenesis, through activation of deleted in colorectal cancer (DCC) receptors. We report here the development of a nanofiber-shaped supramolecular mimetic of netrin-1 with monomers that incorporate a cyclic peptide sequence as the bioactive component. The mimetic structure was found to activate the DCC receptor in primary cortical neurons using low molar ratios of the bioactive comonomer. The supramolecular nanofibers enhanced neurite outgrowth and upregulated maturation as well as pre- and postsynaptic markers over time, resulting in differences in electrical activity similar to neurons treated with the recombinant netrin-1 protein. The results suggest the possibility of using the supramolecular structure as a therapeutic to promote regenerative bioactivity in CNS injuries.
JTD Keywords: axon growth, axon guidance, cell-migration, colorectal-cancer, dcc, dopaminergic-neurons, force-field, functional recovery, netrin-1, neurite outgrowth, neuronal maturation, neurotrophic factor, neurotrophicfactor mimetic, synapsis, Axon growth, Axons, Cells, cultured, Central nervous system, Coarse-grained model, Nanofibers, Netrin-1, Neurogenesis, Neuronal maturation, Neurons, Neurotrophic factor mimetic, Peptide amphiphile, Synapsis
Villacampa, EG, Larsson, L, Mirzazadeh, R, Kvastad, L, Andersson, A, Mollbrink, A, Kokaraki, G, Monteil, V, Schultz, N, Appelberg, KS, Montserrat, N, Zhang, HB, Penninger, JM, Miesbach, W, Mirazimi, A, Carlson, J, Lundeberg, J, (2021). Genome-wide spatial expression profiling in formalin-fixed tissues Cell Genom 1, 100065 
Formalin-fixed paraffin embedding (FFPE) is the most widespread long-term tissue preservation approach. Here, we report a procedure to perform genome-wide spatial analysis of mRNA in FFPE-fixed tissue sections, using well-established, commercially available methods for imaging and spatial barcoding using slides spotted with barcoded oligo(dT) probes to capture the 3' end of mRNA molecules in tissue sections. We applied this method for expression profiling and cell type mapping in coronal sections from the mouse brain to demonstrate the method's capability to delineate anatomical regions from a molecular perspective. We also profiled the spatial composition of transcriptomic signatures in two ovarian carcinosarcoma samples, exemplifying the method's potential to elucidate molecular mechanisms in heterogeneous clinical samples. Finally, we demonstrate the applicability of the assay to characterize human lung and kidney organoids and a human lung biopsy specimen infected with SARS-CoV-2. We anticipate that genome-wide spatial gene expression profiling in FFPE biospecimens will be used for retrospective analysis of biobank samples, which will facilitate longitudinal studies of biological processes and biomarker discovery.© 2021 The Authors.
JTD Keywords: colonic transit, gut, intestinal motility, ld score regression, metaanalysis, nervous-system, neurotrophic factor, population, severity, Covid-19, Ffpe, Genome-wide, Irritable-bowel-syndrome, Mouse brain, Organoids, Ovarian carcinosarcoma, Pfa, Sars-cov-2, Spatial transcriptomics, Visium
