Abstract: The present invention relates to the development of and use of genetically modified human differentiated cells coupled with xenotransplantation into animal models to identify injury and disease-specific RNA and/or protein biomarkers. Specifically, the present invention encompasses two complementary methods for biomarker discovery that enable the direct and selective labelling, isolation, and analysis of human-specific RNA and/or proteins from xenotransplantation (or chimeric) animal models. Both methods involve the treatment of animal models with an RNA analog and/or amino acid analog that enables the specific isolation and quantification of human RNAs and/or proteins for the identification of novel human biomarkers for a large array of human injuries and diseases.

Abstract: Microglia/monocytes exist within a ‘niche’ which limits the total number of microglia/monocytes/macrophages that reside within a mammalian central nervous system (CNS). Therefore, methods are needed that can help therapeutically modify microglia, monocytes, and macrophages or the cells that give rise to them to compete with endogenous microglia and partially or completely occupy the CNS niche. The present disclosure features therapeutic microglia, monocytes, or macrophages that have a selective advantage in comparison to endogenous brain resident microglia in their response to CSF1R inhibitors. Specifically, therapeutic cells developed in the present disclosure do not die at a given dose of CSF1R inhibitor that is sufficient to kill endogenous microglia. The therapeutic cells described herein can be used to treat neurological diseases.

Abstract: Microglia/monocytes exist within a ‘niche’ which limits the total number of microglia/monocytes/macrophages that reside within a mammalian central nervous system (CNS). Therefore, methods are needed that can help therapeutically modify microglia, monocytes, and macrophages or the cells that give rise to them to compete with endogenous microglia and partially or completely occupy the CNS niche. The present disclosure features therapeutic microglia, monocytes, or macrophages that have a selective advantage in comparison to endogenous brain resident microglia in their response to CSF1R inhibitors. Specifically, therapeutic cells developed in the present disclosure do not die at a given dose of CSF1R inhibitor that is sufficient to kill endogenous microglia. The therapeutic cells described herein can be used to treat neurological diseases.

Abstract: Systems for allowing adjustable imaging of specimens of various sizes in solutions of various refractive indices, such as those with a refractive index of at least 1.45, for use in microscopes such as fluorescent light sheet microscopes. The systems allow for imaging large specimens in various refractive indices while maintaining the highest optical sectioning provided by the objectives used across the full range of microscope stage travel. The systems also allow the use of a wider range of optics, such as low magnification 2.5× detection objectives, allowing for increased imaging speed and field of view.

Abstract: Systems for allowing imaging of large specimens in high refractive index solutions, such as those with a refractive index of at least 1.45, for use in microscopes such as fluorescent light sheet microscopes. The systems allow for imaging large specimens in high RI while maintaining the highest optical sectioning provided by the objectives used across the full range of microscope stage travel. The systems also allow the use of a wider range of optics, such as low magnification 2.5× detection objectives, allowing for increased imaging speed and field of view.

Abstract: Systems for allowing adjustable imaging of specimens of various sizes in solutions of various refractive indices, such as those with a refractive index of at least 1.45, for use in microscopes such as fluorescent light sheet microscopes. The systems allow for imaging large specimens in various refractive indices while maintaining the highest optical sectioning provided by the objectives used across the full range of microscope stage travel. The systems also allow the use of a wider range of optics, such as low magnification 2.5× detection objectives, allowing for increased imaging speed and field of view.