Stanford Advisors


All Publications


  • Genomic and transcriptomic profiling of carcinogenesis in patients with familial adenomatous polyposis GUT Li, J., Wang, R., Zhou, X., Wang, W., Gao, S., Mao, Y., Wu, X., Guo, L., Liu, H., Wen, L., Fu, W., Tang, F. 2020; 69 (7): 1283-+

    Abstract

    Familial adenomatous polyposis (FAP) is characterised by the development of hundreds to thousands of adenomas at different evolutionary stages in the colon and rectum that will inevitably progress to adenocarcinomas if left untreated. Here, we investigated the genetic alterations and transcriptomic transitions from precancerous adenoma to carcinoma.Whole-exome sequencing, whole-genome sequencing and single-cell RNA sequencing were performed on matched adjacent normal tissues, multiregionally sampled adenomas at different stages and carcinomas from six patients with FAP and one patient with MUTYH-associated polyposis (n=56 exomes, n=56 genomes and n=8,757 single cells). Genomic alterations (including copy number alterations and somatic mutations), clonal architectures and transcriptome dynamics during adenocarcinoma carcinogenesis were comprehensively investigated.Genomic evolutionary analysis showed that adjacent lesions from the same patient with FAP can originate from the same cancer-primed cell. In addition, the tricarboxylic acid cycle pathway was strongly repressed in adenomas and was then slightly alleviated in carcinomas. Cells from the 'normal' colon epithelium of patients with FAP already showed metabolic reprogramming compared with cells from the normal colon epithelium of patients with sporadic colorectal cancer.The process described in the previously reported field cancerisation model also occurs in patients with FAP and can contribute to the formation of adjacent lesions in patients with FAP. Reprogramming of carbohydrate metabolism has already occurred at the precancerous adenoma stage. Our study provides an accurate picture of the genomic and transcriptomic landscapes during the initiation and progression of carcinogenesis, especially during the transition from adenoma to carcinoma.

    View details for DOI 10.1136/gutjnl-2019-319438

    View details for Web of Science ID 000569655200018

    View details for PubMedID 31744909

    View details for PubMedCentralID PMC7306982

  • Reconstituting the transcriptome and DNA methylome landscapes of human implantation NATURE Zhou, F., Wang, R., Yuan, P., Ren, Y., Mao, Y., Li, R., Lian, Y., Li, J., Wen, L., Yan, L., Qiao, J., Tang, F. 2019; 572 (7771): 660-+

    Abstract

    Implantation is a milestone event during mammalian embryogenesis. Implantation failure is a considerable cause of early pregnancy loss in humans1. Owing to the difficulty of obtaining human embryos early after implantation in vivo, it remains unclear how the gene regulatory network and epigenetic mechanisms control the implantation process. Here, by combining an in vitro culture system for the development human embryos after implantation and single-cell multi-omics sequencing technologies, more than 8,000 individual cells from 65 human peri-implantation embryos were systematically analysed. Unsupervised dimensionality reduction and clustering algorithms of the transcriptome data show stepwise implantation routes for the epiblast, primitive endoderm and trophectoderm lineages, suggesting robust preparation for the proper establishment of a mother-to-offspring connection during implantation. Female embryos showed initiation of random X chromosome inactivation based on analysis of parental allele-specific expression of X-chromosome-linked genes during implantation. Notably, using single-cell triple omics sequencing analysis, the re-methylation of the genome in cells from the primitive endoderm lineage was shown to be much slower than in cells of both epiblast and trophectoderm lineages during the implantation process, which indicates that there are distinct re-establishment features in the DNA methylome of the epiblast and primitive endoderm-even though both lineages are derived from the inner cell mass. Collectively, our work provides insights into the complex molecular mechanisms that regulate the implantation of human embryos, and helps to advance future efforts to understanding early embryonic development and reproductive medicine.

    View details for DOI 10.1038/s41586-019-1500-0

    View details for Web of Science ID 000483405500055

    View details for PubMedID 31435013

  • Single-cell RNA-seq reveals the diversity of trophoblast subtypes and patterns of differentiation in the human placenta CELL RESEARCH Liu, Y., Fan, X., Wang, R., Lu, X., Dang, Y., Wang, H., Lin, H., Zhu, C., Ge, H., Cross, J. C., Wang, H. 2018; 28 (8): 819-832

    Abstract

    The placenta is crucial for a successful pregnancy and the health of both the fetus and the pregnant woman. However, how the human trophoblast lineage is regulated, including the categorization of the placental cell subtypes is poorly understood. Here we performed single-cell RNA sequencing (RNA-seq) on sorted placental cells from first- and second-trimester human placentas. New subtypes of cells of the known cytotrophoblast cells (CTBs), extravillous trophoblast cells (EVTs), Hofbauer cells, and mesenchymal stromal cells were identified and cell-type-specific gene signatures were defined. Functionally, this study revealed many previously unknown functions of the human placenta. Notably, 102 polypeptide hormone genes were found to be expressed by various subtypes of placental cells, which suggests a complex and significant role of these hormones in regulating fetal growth and adaptations of maternal physiology to pregnancy. These results document human placental trophoblast differentiation at single-cell resolution and thus advance our understanding of human placentation during the early stage of pregnancy.

    View details for DOI 10.1038/s41422-018-0066-y

    View details for Web of Science ID 000441069300005

    View details for PubMedID 30042384

    View details for PubMedCentralID PMC6082907

  • Tracing the temporal-spatial transcriptome landscapes of the human fetal digestive tract using single-cell RNA-sequencing NATURE CELL BIOLOGY Gao, S., Yan, L., Wang, R., Li, J., Yong, J., Zhou, X., Wei, Y., Wu, X., Wang, X., Fan, X., Yan, J., Zhi, X., Gao, Y., Guo, H., Jin, X., Wang, W., Mao, Y., Wang, F., Wen, L., Fu, W., Ge, H., Qiao, J., Tang, F. 2018; 20 (6): 721-734

    Abstract

    The development of the digestive tract is critical for proper food digestion and nutrient absorption. Here, we analyse the main organs of the digestive tract, including the oesophagus, stomach, small intestine and large intestine, from human embryos between 6 and 25 weeks of gestation as well as the large intestine from adults using single-cell RNA-seq analyses. In total, 5,227 individual cells are analysed and 40 cell types clearly identified. Their crucial biological features, including developmental processes, signalling pathways, cell cycle, nutrient digestion and absorption metabolism, and transcription factor networks, are systematically revealed. Moreover, the differentiation and maturation processes of the large intestine are thoroughly investigated by comparing the corresponding transcriptome profiles between embryonic and adult stages. Our work offers a rich resource for investigating the gene regulation networks of the human fetal digestive tract and adult large intestine at single-cell resolution.

    View details for DOI 10.1038/s41556-018-0105-4

    View details for Web of Science ID 000433237300013

    View details for PubMedID 29802404