Scientists from Tongji University School of Medicine, Nanjing Medical University and the University of California, Los Angeles have used powerful single-cell RNA sequencing technology to track the genetic development of human and mouse embryos with unprecedented levels of precision. This technology allows researchers to diagnose genetic diseases earlier and more accurately, even at the 8-cell stage. Dr. Zhigang Xue of Tongji University School of Medicine, Professor Jia-yin Liu of Nanjing Medical University, and Guoping Fan, a professor of human genetics and molecular biology at the University of California, Los Angeles, shared the paper. Corresponding Author. The results of the study were published online in the journal Nature.
Single-cell RNA sequencing allows researchers to determine the precise state of all gene transcripts in a particular cell, or all genes that are actively expressed. Fan Guoping said: "The technology has two advantages. It can achieve a more comprehensive analysis than before, and the technology requires only a very small amount of sample material-1 cell." In addition to being used for genetic diagnosis, improve the identification of scientists such as The ability of genetic mutations such as BRCA1 and BRCA2 (causing women to be susceptible to breast and ovarian cancer), or the ability to diagnose genetic diseases caused by protein dysfunction, such as sickle cell disease, this technology can also play an important role in reproductive medicine the use of.
This technology marks an important advancement in genetic diagnosis. Previously, genetic diagnosis could not be performed in the early stage of embryonic development, and a larger amount of biological materials was required. In the new study, scientists used the RNA-seq technology of single-cell expression profiling to break through the bottleneck of a small initial sample size, and systematically analyzed the whole-genome RNA transcription profiles of human embryos at various stages of early development and found that they were found in embryo development. In the early stages, there were differences in the expression of single alleles from father or mother.
At the same time, using weighted gene co-expression network analysis (WGCNA) showed that the cell cycle, gene regulation, protein translation and transcriptional changes of metabolic pathways in each stage of early embryonic development occurred sequentially in a step-by-step manner, and it was clear that the mechanism is Conservation exists between species, only differing in development specificity and timing, which proves the evolutionary commonness of early embryonic development in mammals. In addition, the study also identified key candidate genes that drive various stages of early embryonic development. Kevin Huang, a co-first author of the paper and a postdoctoral fellow in Fan Guoping's laboratory, said: "Before this paper, we didn't know much about early human development. Now we can define its 'normal' appearance, so for our sake This is a benchmark to compare possible genetic problems. This is the first time we have looked at the normal situation comprehensively. "
Using single-cell RNA sequencing, much more gene transcription was detected than before. Fan Guoping said: "Our question is," How does this gene network drive early development from 1 cell to 2 cells, from 2 cells to 4 cells, and so on? "Using co-authors, the University of California The genomic data analysis method developed by Steve Horvath of the University of Los Angeles has revealed important gene networks, and we can now predict possible future genetic diseases at the 8-cell stage. "
This research was supported by the Ministry of Science and Technology of China, China International Science and Technology Cooperation Project and China National Natural Science Foundation.
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