Project description:Ovotestis often occurs in intersex individuals under certain pathological and physiological conditions. However, how ovotestis is formed remains unknown. Here, we report the first comprehensive single-cell developmental atlas of the model fish ovotestis. We provide an overview of ovotestis cell identities and a roadmap of germline, niche, and stem cell development in ovotestis by cell lineage reconstruction and a uniform manifold approximation and projection. We identify common progenitors of germline stem cells with two states, which reveal their bipotential nature to differentiate into both spermatogonial stem cells and female germline stem cells. Moreover, we found that ovotestis infertility was caused by developmental defects in oogenesis owing to dynamic autophagic degradation in female germline cells, and in spermatogenesis due to deficiency of histone-to-protamine replacement in spermatid differentiation. Notably, signaling pathways in gonadal niche cells and their interaction with germline cells synergistically determined cell fates of both male and female germlines in ovotestis. Overall, we reveal a cellular fate map of germline and niche cell development that shapes cell differentiation directions of ovotestis, and provide novel insights into ovotestis development.
Project description:Human cerebellar development is precisely orchestrated by molecular regulatory networks. Here, we combined single-cell transcriptomics, spatial transcriptomics and chromatin accessibility states to systematically depict an integrative temporal-spatial landscape of human fetal cerebellar development. The multiomic data reveal molecular networks, providing an informative regulatory map to show how and when cell fates are determined. Spatial transcriptomics illustrated the distinct molecular signatures of the progenitors, Purkinje cells and granule cells located in different regions of the developing cerebellar cortex. We identified RORB as a new marker of developing human Purkinje cells, which was not expressed in mice. In addition, the RL progenitors highly expressed the human-specific gene ARHGAP11B , and ARHGAP11B expression led to cerebellar cortex expansion and folding in mice. We finally mapped the genes and single-nucleotide polymorphisms (SNPs) of diseases related to cerebellar dysfunction onto cell types, indicating the cellular basis and possible pathogenesis mechanisms of neuropsychiatric disorders.