On September 25^th, 2019, Prof Fuchou Tang and Dr Lu Wen at BIOPIC were invited to publish review on Molecular Cell, to summarize recent progresses on single-cell sequencing for human germline cell development.

Germ cells are the beginning of new individuals in multicellular animals including humans and are also the driving force of genetic diversity and evolution. They include a totipotent zygote derived from fusion of an oocyte and a sperm, the pluripotent inner cell mass (ICM) and peri-implantation epiblasts (EPI), the unipotent fetal germ cells (FGCs), postnatal germ cells and finally the mature oocytes and sperms, which make a complete germline developmental circle (Figure 1). Germline cells are ‘immortal’ during the millions of years of the evolutionary life of a species, and they can develop into non-germline cells, but not vice versa.

Prof Tang Fuchou’s lab has developed a serial of single-cell transcriptome, DNA methylome and chromatin accessibility sequencing technologies (Genome Research, 2013; PNAS, 2014; Genome Biology, 2015; Cell Research, 2016; Cell Stem Cell, 2017; Cell Research, 2017; Science Bulletin, 2017). Using these technologies, Prof. Tang Fuchou’s lab, in colaboration with Prof. Jie Qiao’s lab, have systematically explored the dynamic transcriptome and epigenome at single-cell-resolution during human germline development. As early as 2013, the team has mapped the transcriptome of human preimplantation development at single-cell resolution (Nature Structural &Molecular Biology, 2013). Then, they have dissected two global waves of DNA methylation reprogramming of human preimplantation development and fetal germ cell development using a RRBS-based single cell DNA methylome technology (Figure 2; Guo et al. Nature，2014；Guo et al. Cell，2015). Then, they have more systematcially interrogated the DNA methylomes of human preimplantation development using a PBAT-based single cell DNA methylome technology. They illustrated the balance of demethylation and de novo DNA methylation, as well as methylation divergency between parental genomes during the preimplantation epigenetic reprogramming process (Figure 2; Zhu, et al. Nature Genetics, 2018). Using scCOOL-seq, a single-cell multi-omics epigenome sequencing technique (Guo, et al. Cell Research, 2017), the team has resolved the key characters of DNA methylome and chromatin accessibility reprogramming during human preimplantation development (Li, et al. Nature Cell Biology, 2018）. Prof Fuchou Tang’s group, collaborating with Prof Jie Qiao’s group, has mapped development of human fetal germ cells and gonadal niche interactions (Figure 3, Li et al. Cell Stem Cell, 2017); and collaborating with Prof Xiaoyang Zhao’s group, has also mapped human adult spermatogenesis using scRNA-seq (Figure 4, Wang et al. Cell Stem Cell, 2018）. Most recently, Prof Fuchou Tang’s group, collaborating with Prof Jie Qiao’s group, has reconstituted the transcriptome and DNA methylome landscapes of human implantation development using scRNA-seq and scTrio-seq (Zhou et al. Nature, 2019).

Prof Fuchou Tang’s group, together with other scientists in the world, are charting a more complete epigenome atlas of human germline cell development in the near future. These highly accurate maps of human normal germline cell development should also help a better molecular understanding of the developmental abnormalities of human infertility that occur in approximately 10%–15% of couples of reproductive age.

Figure 1. Human germline cycle

Figure 2. DNA methylation reprogramming of human germline cells.

Figure 3. Single-cell transcriptomics of human fetal germ cells.

Figure 4. Single-cell transcriptomics of human adult spermatogenesis.