<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Development and Evolution of the Mammalian Cerebellum at Single Cell Resolution"^^ . "Originally thought to only take part in motor control, the cerebellum emerged over the last decades\r\nas an important organ in various higher cognitive functions, such as learning and speech. Besides this, the cerebellum is associated to various diseases, such as spinocerebellar ataxia, autism spectrum disorder, and medulloblastoma. The basic structure and connective properties of it\r\nare well understood, but single-cell-technologies made it possible to study the cerebellum at higher\r\nresolution. Many questions about molecular details of its development and evolution are still not\r\nanswered. Cerebella are present in all jawed vertebrates, though structural diversity is macroscopic\r\nand microscopic detectable, such as the number of deep nuclei, the presence of the vermis, or the\r\nmode of production of one of the most important cell types in the cerebellum - granule cells.\r\nUsing single-nucleus RNA-sequencing (snRNA-seq) and bioinformatic approaches, I studied cerebellum data of human, mouse (Mus musculus) and opossum (Monodelphis domestica). The dataset\r\ncontained samples spanning the organs development at high temporal resolution. It was possible\r\nto track the differentiation of the major cerebellar neuronal and glial cell types, as well as identify\r\nstates and subtypes. This generated a comprehensive map of cellular complexity through eutherian\r\n(human and mouse) and marsupial (opossum) development. Leveraging the evolutionary distance\r\nof approximately 160 million years between the eutherian and marsupial lineage, conserved and\r\ndiverged cell type marker genes could be identified which might be promising candidates for understanding the basic blueprint of cerebellar cell type identity.\r\nStage correspondence mapping aligned the vastly different developmental time frames of the\r\nthree studied species and allowed the identification of a two-fold increase in Purkinje cell progenitors\r\nin the human lineage, which might be connected to a recently identified human-specific secondary\r\nventricular zone progenitor pool.\r\nIt was possible to model the differentiation path of granule and Purkinje cells from early progenitors to mature neurons. Conserved and diverged gene expression trajectories were discovered.\r\nUsing in vitro and in vivo intollerance scores, I could show that genes which are dynamically\r\nexpressed during differentiation show higher functional constraint as non-dynamic genes, fitting to\r\nprevious bulk-RNA-seq studies, showing similar results across the development of the full organ.\r\nSome orthologs with diverging patterns were disease-associated genes, which could have implications\r\non clinical research on conditions like autism spectrum disorders and medulloblastoma.\r\nFurthermore, fundamental changes of gene expressions, established as gain or loss of expression\r\nwithin a cell type and species, were detected. Affected genes showed decreased functional constraint,\r\nverifying evolutionary principles on single cell scale.\r\nTaken together, this study shows the strength of state of the art methodology combined with\r\nhigh resolution developmental sampling in an evolution biological context to discover fundamental\r\nprinciples of organ development at single-cell scale."^^ . "2023" . . . . . . . "Kevin"^^ . "Leiß"^^ . "Kevin Leiß"^^ . . . . . . "Development and Evolution of the Mammalian Cerebellum at Single Cell Resolution (PDF)"^^ . . . "PhD_Thesis_Kevin_Leiss.pdf"^^ . . . "Development and Evolution of the Mammalian Cerebellum at Single Cell Resolution (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Development and Evolution of the Mammalian Cerebellum at Single Cell Resolution (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Development and Evolution of the Mammalian Cerebellum at Single Cell Resolution (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Development and Evolution of the Mammalian Cerebellum at Single Cell Resolution (Other)"^^ . . . . . . "small.jpg"^^ . . . "Development and Evolution of the Mammalian Cerebellum at Single Cell Resolution (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #33049 \n\nDevelopment and Evolution of the Mammalian Cerebellum at Single Cell Resolution\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .