Obesity,which can arise from genetic or environmental factors,has been shown to cause serious damages to the reproductive system.The ovary,as one of the primary regulators of female fertility,is a complex organ compri...Obesity,which can arise from genetic or environmental factors,has been shown to cause serious damages to the reproductive system.The ovary,as one of the primary regulators of female fertility,is a complex organ comprised of heterogeneous cell types that work together to maintain a normal ovarian microenvironment(OME).Despite its importance,the effect of obesity on the entire ovary remains poorly documented.In this study,we performed ovary single-cell and nanoscale spatial RNA sequencing to investigate how the OME changed under different kinds of obesity,including high-fat diet(HFD)induced obesity and Leptin ablation induced obesity(OB).Our results demonstrate that OB,but not HFD,dramatically altered the proportion of ovarian granulosa cells,theca-interstitial cells,luteal cells,and endothelial cells.Furthermore,based on the spatial dynamics of follicular development,we defined four subpopulations of granulosa cell and found that obesity drastically disrupted the differentiation of mural granulosa cells from small to large antral follicles.Functionally,HFD enhanced follicle-stimulating hormone(FSH)sensitivity and hormone conversion,while OB caused decreased sensitivity,inadequate steroid hormone conversion,and impaired follicular development.These differences can be explained by the differential expression pattern of the transcription factor Foxo1.Overall,our study provides a powerful and high-resolution resource for profiling obesity-induced OME and offers insights into the diverse effects of obesity on female reproductive disorders.展开更多
Data visualization empowers researchers to communicate their results that support scientific reasoning in an intuitive way.Three-dimension(3D)spatially resolved transcriptomic atlases constructed from multi-view and h...Data visualization empowers researchers to communicate their results that support scientific reasoning in an intuitive way.Three-dimension(3D)spatially resolved transcriptomic atlases constructed from multi-view and high-dimensional data have rapidly emerged as a powerful tool to unravel spatial gene expression patterns and cell type distribution in biological samples,revolutionizing the understanding of gene regulatory interactions and cell niches.However,limited accessible tools for data visualization impede the potential impact and application of this technology.Here we introduce VT3D,a visualization toolbox that allows users to explore 3D transcriptomic data,enabling gene expression projection to any 2D plane of interest,2D virtual slice creation and visualization,and interactive 3D data browsing with surface model plots.In addition,it can either work on personal devices in standalone mode or be hosted as a web-based server.We apply VT3D to multiple datasets produced by the most popular techniques,including both sequencing-based approaches(Stereo-seq,spatial transcriptomics,and Slide-seq)and imaging-based approaches(MERFISH and STARMap),and successfully build a 3D atlas database that allows interactive data browsing.We demonstrate that VT3D bridges the gap between researchers and spatially resolved transcriptomics,thus accelerating related studies such as embryogenesis and organogenesis processes.The source code of VT3D is available at https://github.com/BGI-Qingdao/VT3D,and the modeled atlas database is available at http://www.bgiocean.com/vt3d_example.展开更多
基金This work was supported by the National Key Research and Development Program of China(2021YFC2700400,2018YFC1004303)the National Natural Science Foundation of China(31988101,82201798,82192874,82071606,82101707)+3 种基金CAMS Innovation Fund for Medical Sciences(2021-I2M-5-001)Shandong Provincial Key Research and Development Program(2020ZLYS02)the Taishan Scholars Program of Shandong Province(ts20190988)the Fundamental Research Funds of Shandong University.
文摘Obesity,which can arise from genetic or environmental factors,has been shown to cause serious damages to the reproductive system.The ovary,as one of the primary regulators of female fertility,is a complex organ comprised of heterogeneous cell types that work together to maintain a normal ovarian microenvironment(OME).Despite its importance,the effect of obesity on the entire ovary remains poorly documented.In this study,we performed ovary single-cell and nanoscale spatial RNA sequencing to investigate how the OME changed under different kinds of obesity,including high-fat diet(HFD)induced obesity and Leptin ablation induced obesity(OB).Our results demonstrate that OB,but not HFD,dramatically altered the proportion of ovarian granulosa cells,theca-interstitial cells,luteal cells,and endothelial cells.Furthermore,based on the spatial dynamics of follicular development,we defined four subpopulations of granulosa cell and found that obesity drastically disrupted the differentiation of mural granulosa cells from small to large antral follicles.Functionally,HFD enhanced follicle-stimulating hormone(FSH)sensitivity and hormone conversion,while OB caused decreased sensitivity,inadequate steroid hormone conversion,and impaired follicular development.These differences can be explained by the differential expression pattern of the transcription factor Foxo1.Overall,our study provides a powerful and high-resolution resource for profiling obesity-induced OME and offers insights into the diverse effects of obesity on female reproductive disorders.
基金supported by the General Program(Key Program,Major Research Plan)of National Natural Science Foundation of China(No.32170439).
文摘Data visualization empowers researchers to communicate their results that support scientific reasoning in an intuitive way.Three-dimension(3D)spatially resolved transcriptomic atlases constructed from multi-view and high-dimensional data have rapidly emerged as a powerful tool to unravel spatial gene expression patterns and cell type distribution in biological samples,revolutionizing the understanding of gene regulatory interactions and cell niches.However,limited accessible tools for data visualization impede the potential impact and application of this technology.Here we introduce VT3D,a visualization toolbox that allows users to explore 3D transcriptomic data,enabling gene expression projection to any 2D plane of interest,2D virtual slice creation and visualization,and interactive 3D data browsing with surface model plots.In addition,it can either work on personal devices in standalone mode or be hosted as a web-based server.We apply VT3D to multiple datasets produced by the most popular techniques,including both sequencing-based approaches(Stereo-seq,spatial transcriptomics,and Slide-seq)and imaging-based approaches(MERFISH and STARMap),and successfully build a 3D atlas database that allows interactive data browsing.We demonstrate that VT3D bridges the gap between researchers and spatially resolved transcriptomics,thus accelerating related studies such as embryogenesis and organogenesis processes.The source code of VT3D is available at https://github.com/BGI-Qingdao/VT3D,and the modeled atlas database is available at http://www.bgiocean.com/vt3d_example.
