Project description:Axon regeneration in the central nervous system (CNS) requires reactivating injured neurons’ intrinsic growth state and enabling growth in an inhibitory environment. Using an inbred mouse neuronal phenotypic screen, we find that CAST/Ei mouse adult dorsal root ganglion neurons extend axons more on CNS myelin than the other eight strains tested, especially when pre-injured. Injury-primed CAST/Ei neurons also regenerate markedly in the spinal cord and optic nerve more than those from C57BL/6 mice and show greater spouting following ischemic stroke. Heritability estimates indicate that extended growth in CAST/Ei neurons on myelin is genetically determined, and two whole-genome expression screens yield the Activin transcript Inhba as most correlated with this ability. These screens are presented here.
Project description:There is a critical unmet need to image 2D materials within single cells and tissues. Here we propose a versatile label-free single-cell detection strategy based on mass cytometry. We use single-cell mass cytometry by time-of-flight (CyTOF), imaging mass cytometry, and multiplexed ion beam imaging by time-of-flight (MIBI-TOF) with three representative MXenes. Nb4C3, Mo2Ti2C3, and Ta4C3 were selected to ensure mass-detection within the range and to avoid overlap with currently available tags. We demonstrated their biocompatibility, detection, and quantification in 16 primary human immune cell subpopulations also showing the impact of MXene lateral size on the detection signal and cell binding. We report the biological and immune functional compatibility of MXenes. In vivo biodistribution experiments in mice using a mixture of MXenes revealed their presence in liver, blood, spleen, and lungs. Lastly, we applied MIBI-TOF to capture the presence of MXenes in different organs. The label-free detection of 2D materials by mass cytometry at the single cell level, on multiple subpopulations and in multiple organs in vivo opens exciting new opportunities in biomedicine.
Project description:Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect with a world-wide prevalence of 3 to 4 cases per 10,000 life births. TOF is a congenital heart disease with four major cardiac defects, i.e., ventricular septal defect, overriding aortic root, infundibular stenosis of the pulmonary artery, and right ventricular hypertrophy. Treatment relies on correction surgery in early infancy. This study performed whole genome microarray gene expression profiling of cardiac specimens of the right ventricular outflow tract (RVOT), which were recovered during correction surgery of TOF from 11 pediatric patients diagnosed with TOF cardiac defects.
Project description:Mouse genetic crosses were established between the PyMT model of metastatic breast cancer and MOLF/Ei strain. Tumors were harvested from the animals for gene expression analysis to identify genes associated with progression to distant metastatic disease.
Project description:We screened nine genetically diverse inbred mouse strains for differences in axonal growth of adult dorsal root ganglion (DRG) neurons on CNS myelin. Naïve DRG neurite outgrowth on myelin was very limited, but preconditioning the neurons by a prior sciatic nerve crush increased axonal growth substantially across all strains, with by far the greatest change in neurons from CAST/Ei mice. Three independent in vivo CNS injury models revealed greater capacity for CNS axonal regeneration in CAST/Ei than C57BL/6 mice. Full-genome expression profiling of naïve and pre-conditioned DRGs across all strains revealed Activin-βA (Inhba) as the transcript whose expression most closely correlated with axonal growth on myelin. In vitro and in vivo gain- and loss-of-function experiments confirmed that Activin promotes axonal growth in the CNS. Substantial regeneration is possible, therefore, in the injured mammalian CNS when Activin signaling is intrinsically high, as in CAST/Ei or when extrinsically modulated in other strains.