<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Building and exploring enhancer-gene regulatory networks governing Drosophila spermatogenesis"^^ . "Cellular behaviors involved in stem cell regulation, growth, differentiation, and development are\r\ncrucial progresses in the development and maintenance of lineages. Cells coordinate such\r\nbehavior through communications by various mechanisms, including direct cell-cell interactions\r\nand diffusible signaling molecules, to synchronize their actions and maintain the health and\r\ncomplexity of the entire organism. This perceived signaling subsequently directs molecular\r\nprograms consisting of specific sets of genes, which are activated by genomic cis regulatory\r\nelements (CREs) in response to various signals, and encode proteins that guide and execute\r\ncritical processes such as cell differentiation, growth, and adaptation to environmental changes.\r\nTherefore, understanding how these programs are encoded and regulated provides insight into\r\nthe fundamental mechanisms of cellular behavior.\r\nThe Drosophila testis provides an excellent model for this; two stem cells at the niche compete\r\nfor self-renewal signals, germline stem cell and somatic cyst stem cell, while maintaining a fine\r\nbalance. The germline will differentiate and progress through dramatic transcriptional and\r\ngenomic changes, all necessary for the formation of compacted and motile sperm. In the process,\r\nthe somatic cyst lineage supports spermatogenesis, a tightly controlled process that is\r\ncoordinated by extensive signaling between the two lineages.\r\nTherefore, to understand the regulatory logic behind cellular decision making, I simultaneously\r\nprofiled the transcriptomes and chromatin accessibility profiles within 10,335 individual nuclei.\r\nIn doing so, I identify over 90% of the Drosophila protein-coding genome being transcribed in the\r\ntestis, with dynamics equal to published testis transcriptomes. Furthermore, I identified 46,619\r\naccessible regions across all cell stages, with 14,577 of those regions showing differential\r\naccessibility. Leveraging both modalities, I constructed the first testis-specific enhancer-driven\r\ngene regulatory network (eGRN), revealing 103 activating and 44 repressing TF eRegulons in the\r\ntestis, with cell specificity. Validation of the testis eGRN by means of in vivo eRegulon TF\r\nperturbations are consistent with their putative functions, or can be rationalized within the scope\r\nof spermatogenesis.\r\nFurthermore, cooperative regulation between eRegulons is characterized by the joint binding to\r\ncommon regulatory regions to induce the expression of sets of differential targets throughout\r\nspermatogenesis. Moreover, lineage specific CRISPR-mediated mutagenesis of either cooperating\r\novo or klu TFs resulted in the downregulation of their common target stg, a mitotic inducer. This\r\nreveals that eGRN prediction can facilitate the elucidation of novel roles for uncharacterized TFs\r\nin the testis.\r\nLastly, by expanding on cell-cell communication, the previously not well characterized Wnt\r\npathway was predicted to be active in the testis, as well as its downstream effector pan/TCF. In\r\nvivo characterization indicates that Wnt components are involved in the modulation of stem cell\r\nnumbers, in particular the GSCs."^^ . "2025" . . . . . . . "Patrick"^^ . "van Nierop y Sanchez"^^ . "Patrick van Nierop y Sanchez"^^ . . . . . . "Building and exploring enhancer-gene regulatory networks governing Drosophila spermatogenesis (PDF)"^^ . . . "Building and exploring enhancer-gene regulatory networks governing Drosophila spermatogenesis (Other)"^^ . . . . . . "Building and exploring enhancer-gene regulatory networks governing Drosophila spermatogenesis (Other)"^^ . . . . . . "Building and exploring enhancer-gene regulatory networks governing Drosophila spermatogenesis (Other)"^^ . . . . . . "Building and exploring enhancer-gene regulatory networks governing Drosophila spermatogenesis (Other)"^^ . . . . . . "Building and exploring enhancer-gene regulatory networks governing Drosophila spermatogenesis (Other)"^^ . . . . . "HTML Summary of #36323 \n\nBuilding and exploring enhancer-gene regulatory networks governing Drosophila spermatogenesis\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . .