Project description:Here, we constructed monkey blastoids resembling blastocysts in morphology and transcriptomics using naïve ESCs and optimized protocol. The synthetic blastoids could develop to embryonic disk stage with the structure of yolk sac, chorionic cavity, amnion cavity, primitive streak, connecting stalk along the rostral–caudal axis by in-vitro prolonged culture (IVC). Primordial germ cells, gastrulating cells, visceral endoderm/yolk-sac endoderm, three germ layers and haemato-endothelial progenitors were identified in the monkey blastoid IVC embryo by single-cell transcriptomics or immunostaining. Besides, pregnancies with early gestation sacs were achieved by transferring monkey blastoids to surrogates. Our results revealed the in-vitro gastrulation and in-vivo early pregnancy of primate synthetic embryos, providing a powerful system to dissect primate embryonic development with less ethical concerns and restrict access.
Project description:With improved whole-cell isolation protocols, we performed single-cell RNA sequencing (scRNA-seq) and profiled the transcriptomes from adult non-human primate brain. We identified discriminative cell populations with canonical and novel markers. Cross-species projection demonstrated the evolutionary conservation among mouse, monkey, and human. This dataset serves as a detailed transcriptomic atlas for understanding the adult primate central nervous system.
Project description:Macaca fascicularis (long-tailed, cynomolgus, or crab-eating macaque) is a highly advantageous model in which to study human cochlea with regard to both evolutionary proximity and physiological similarity of the auditory system. To better understand the properties of primate cochlear function, we analyzed the genes predominantly expressed in M. fascicularis cochlea.
Project description:During mammalian embryogenesis, temporal and spatial regulation of gene expression and cell signaling influences lineage specification, the patterning of tissue progenitors and the morphogenesis of embryo. While the mouse model has been instrumental for our understanding of mammalian development, comparatively little is known about early human and non-human primate gastrulation due to the limitation of technical and ethical. Here, we present a morphological and molecular approach that reveals the systematically morphological changes and comprehensive transcriptional landscape of cell types populating the non-human primate embryos during gastrulation.
Project description:The long-tailed macaque, also referred to as cynomolgus monkey (Macaca fascicularis), is one of the most important non-human primate animal models in basic and applied biomedical research. To improve the predictive power of primate experiments for humans, we determined the genome sequence of a Macaca fascicularis female of Mauritian origin using a whole-genome shotgun sequencing approach. We applied a template switch strategy which employs either the rhesus or the human genome to assemble sequence reads. The 6-fold sequence coverage of the draft genome sequence enabled discovery of about 2.1 million potential single-nucleotide polymorphisms based on occurrence of a dimorphic nucleotide at a given position in the genome sequence. Homology-based annotation allowed us to identify 17,387 orthologs of human protein-coding genes in the M. fascicularis draft genome and the predicted transcripts enabled the design of a M. fascicularis-specific gene expression microarray. Using liver samples from 36 individuals of different geographic origin, we identified 718 genes with highly variable expression in liver, whereas the majority of the transcriptome shows relatively stable and comparable expression. Knowledge of the M. fascicularis draft genome is an important contribution to both the use of this animal in disease models and the safety assessment of drugs and their metabolites. In particular, this information allows high-resolution genotyping and microarray-based gene expression profiling for animal stratification, thereby allowing the use of well-characterized animals for safety testing. Finally, the genome sequence presented here is a significant contribution to the global "3R" animal welfare initiative, which has the goal to reduce, refine and replace animal experiments.
Project description:1) Spleen-Liver Immune Axis in Non-Alcoholic Steatohepatitis (NASH) Pathogenesis 2) miRNA Expression Alterations in Primate Model of NASH 3)Targeting the Spleen for Novel NASH Therapeutic Strategies"