Project description:This study presents a comprehensive single-cell RNA sequencing (scRNA-seq) atlas of embryonic development in two distinct Chinese sheep breeds: the cold-adapted Hulunbuir short-tailed sheep (HSTS) and the heat-tolerant Hu sheep (HS). We profiled embryos at two critical developmental timepoints—16 and 19 days post-insemination—to investigate the cellular heterogeneity and molecular mechanisms underlying tail length dimorphism. Our analysis identified 12–15 distinct cell types across samples and revealed MDK_ITGA6+ITGB1 as a central ligand-receptor pair in intercellular communication. We observed that HSTS embryos exhibit premature degeneration of the apical ectodermal ridge (AER), driven by a loss-of-function mutation in the T gene (c.G334T), which dysregulates BMP and FGF signaling pathways. Functional validation in a T mutant mouse model confirmed the role of this mutation in tail shortening. These findings provide insight into the genetic and cellular basis of adaptive tail morphology and offer potential targets for livestock breeding.
Project description:The mammalian body plan is established during symmetry breaking and gastrulation. In ungulates and primates, these events occur within a flat embryonic disc and coincide with the developmental window most susceptible to pregnancy loss. Using the EvercodeTM Cell Fixation kit v2 (ECF2101, Parse Biosciences), we have generated a single-cell RNA sequencing atlas of in vivo sheep embryos that defines the timing and molecular programs underlying lineage segregation, as well as the inter-lineage signalling mediating anterior visceral hypoblast specification (AVH) and primitive streak formation.
Project description:Zygotic genome activation (ZGA) is essential for early embryo development. Here, we reported that ZGA is initiated at 16-cell stage in sheep, as extensive alterations in gene expression and DNA methylation patterns, along with elevated levels of RNA polymerase II and developmental arrest was found at the 16-cell embryos. To uncover the sophisticated RNA metabolism during ZGA, we conducted weighted gene co-expression network analysis and identified 1957 critical maternal genes. Using dapars, we found 1058 and 933 lengthened alternative polyadenylation (APA) events, and genes exhibiting shorten APA were highly expressed in both sheep and mice ZGA-stage embryos. Using rMATs, we reported 2675 and 1963 genes showed exon skipping during ZGA in sheep and mice. These genes are related to RNA binding, translation, gamete generation, and reproduction.
Project description:This model was reconstructed from single-nucleus RNA-seq (snRNA-seq) data of human postmortem brain and curated using published metabolomics data from human iPSC-derived neurons and cerebrospinal fluid (CSF), together with gene expression data from the Human Protein Atlas. It more accurately simulates human neuronal metabolic flux in neurodegenerative conditions such as Alzheimer's disease (AD).
