Project description:Tracing the temporal-spatial transcriptomic landscapes of the human fetal digestive tract by single cell RNA-seq analysis [adult tissues]
Project description:The development of digestion tract is critical for proper digestion of food and absorbance of nutrient for an individual. It includes the spatial segregation into esophagus, stomach, small and large intestine. The temporal-spatial gene expression profiles of human digestion tract in vivo have never been analyzed at single-cell resolution.Here we analyzed esophagus, stomach, small intestine (SI) and large intestine (LI) from multiple human embryos between 6 and 25 weeks of gestation by single cell RNA-seq analyses.We firstly identified 51 clusters of different types of cells using t- Distributed Stochastic Neighbor Embedding (t-SNE) analysis.Moreover,cell type of each organ were identified according to the known marker genes and new cell types were further analyzed.The dynamic change of each cell type were tracked during the human embryonic digestive tract development.We found HOX family geens paly different roles in the regulation of digestion tract developemnt. In addition, Hedgehog,TGFβ and BMP signaling pathway are essential for SI and LI development in human fetal. The function of nutrient digestion and absorption was increased as the SI development in human fetal.Finally, we demonstrated that the immune system was established at late stage of human fetal and verified the immune-like cells,such as T cell, B cells and macrophage. In summary, by using single cell RNA seq technique, we identified the waves of signaling pathways and critical cell types for the human digestion tract development.
Project description:The attachment site of the rotator cuff (RC) is a classic fibrocartilaginous enthesis, which is the junction between bone and tendon with typical characteristics of a fibrocartilage transition zone. Enthesis development has historically been studied with lineage tracing of individual genes selected a priori, which does not allow for the determination of single-cell landscapes yielding mature cell types and tissues. Here, in together with open source GSE182997 datasets (3 sample) provided by Fang et al, we applied Single-cell RNA sequencing (scRNA-seq) to delineate the comprehensive postnatal RC enthesis growth and the temporal atlas from as early as postnatal day 1 up to postnatal week 8. And we furtherly performed single cell spatial transcriptomic sequencing on postnatal day 1 mice enthesis, in order to deconvoluted bone-tendon junction (BTJ) chondrocytes onto spatial spots. In summary, we deciphered the cellular heterogeneity and the molecular dynamics during fibrocartilage differentiation. Combined with current spatial transcriptomic data, our results provide a transcriptional resource that will support future investigations of enthesis development at the mechanistic level and may shed light on the strategies for enhanced RC healing outcomes.
Project description:The coordinated spatial and temporal regulation of gene expression in the murine hindlimb determines the identity of mesenchymal progenitors and the development of diversity of musculoskeletal tissues they form. Hindlimb development has historically been studied with lineage tracing of individual genes selected a priori, or at the bulk tissue level, which does not allow for the determination of single cell transcriptional programs yielding mature cell types and tissues. To identify the cellular trajectories of lineage specification during limb bud development, we used single cell mRNA sequencing (scRNA-seq) to profile the developing murine hindlimb.
Project description:The coordinated spatial and temporal regulation of gene expression in the murine hindlimb determines the identity of mesenchymal progenitors and the development of diversity of musculoskeletal tissues they form. Hindlimb development has historically been studied with lineage tracing of individual genes selected a priori, or at the bulk tissue level, which does not allow for the determination of single cell transcriptional programs yielding mature cell types and tissues. To identify the cellular trajectories of lineage specification during limb bud development, we used single cell mRNA sequencing (scRNA-seq) to profile the developing murine hindlimb.
Project description:The overall objective of this proposal is to map the temporal and spatial dynamics of gene expression in the fetal mouse testis at key developmental timepoints. Urogenital tract malformations are the most common birth defects in males and their incidence together with other male reproductive health concerns such as reduced fertility and testicular cancer are reportedly on the rise in the human population. To better understand the impact of genetic factors and environmental influences on testicular development, it is important to first understand normal gene expression patterns and signaling cascades within the fetal testis during development. The goal of this study is to identify cell-specific genes that can be used as biomarkers for key differentiation events. Experiment Overall Design: Day to day comparison in whole epididymus throughout development with triplicates at each time point. Each sample is a pair of epididymus from a single animal and each animal is taken from a different dam.
Project description:The overall objective of this proposal is to map the temporal and spatial dynamics of gene expression in the fetal mouse testis at key developmental timepoints. Urogenital tract malformations are the most common birth defects in males and their incidence together with other male reproductive health concerns such as reduced fertility and testicular cancer are reportedly on the rise in the human population. To better understand the impact of genetic factors and environmental influences on testicular development, it is important to first understand normal gene expression patterns and signaling cascades within the fetal testis during development. The goal of this study is to identify cell-specific genes that can be used as biomarkers for key differentiation events.
Project description:The overall objective of this proposal is to map the temporal and spatial dynamics of gene expression in the fetal mouse testis at key developmental timepoints. Urogenital tract malformations are the most common birth defects in males and their incidence together with other male reproductive health concerns such as reduced fertility and testicular cancer are reportedly on the rise in the human population. To better understand the impact of genetic factors and environmental influences on testicular development, it is important to first understand normal gene expression patterns and signaling cascades within the fetal testis during development. The goal of this study is to identify cell-specific genes that can be used as biomarkers for key differentiation events. Experiment Overall Design: Day to day comparison in whole ovary throughout development with triplicates at each time point. Each sample is a pair of ovaries from a single animal and each animal is taken from a different dam (with the exception of gd11 sample numbers 18 and 19 which come from the same dam).
Project description:In the early fetal stage, the gonads are bipotent and only later become the ovary or testis, depending on the genetic sex. Despite many studies examining how sex determination occurs from biopotential gonads, the spatial and temporal organization of bipotential gonads and their progenitors is poorly understood. Here, using lineage tracing in mice, we find that the gonads originate from a T+ primitive streak through WT1+ posterior intermediate mesoderm and appear to share origins anteriorly with the adrenal glands and posteriorly with the metanephric mesenchyme. Comparative single cell transcriptomic analyses in mouse and cynomolgus monkey embryos reveals the convergence of the lineage trajectory and genetic programs accompanying the specification of biopotential gonadal progenitor cells. This process involves sustained expression of epithelial genes and upregulation of mesenchymal genes, thereby conferring a unique epithelial/mesenchymal hybrid state. Our study provides key resources for understanding early gonadogenesis in mice and primates.