High-resolution annotation of the mouse preimplantation embryo transcriptome using long-read sequencing

Yunbo Qiao (), Chao Ren, Shisheng Huang, Jie Yuan, Xingchen Liu, Jiao Fan, Jianxiang Lin, Susu Wu, Qiuzhen Chen, Xiaochen Bo, Xiangyang Li, Xingxu Huang, Zhen Liu () and Wenjie Shu ()
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Yunbo Qiao: Guangzhou University
Chao Ren: Beijing Institute of Radiation Medicine
Shisheng Huang: ShanghaiTech University
Jie Yuan: Beijing Institute of Radiation Medicine
Xingchen Liu: University of Chinese Academy of Sciences
Jiao Fan: 2nd Medical Center of Chinese PLA General Hospital
Jianxiang Lin: Guangzhou University
Susu Wu: Guangzhou University
Qiuzhen Chen: Beijing Institute of Radiation Medicine
Xiaochen Bo: Beijing Institute of Radiation Medicine
Xiangyang Li: ShanghaiTech University
Xingxu Huang: ShanghaiTech University
Zhen Liu: Chinese Academy of Sciences
Wenjie Shu: Beijing Institute of Radiation Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract The transcriptome of the preimplantation mouse embryo has been previously annotated by short-read sequencing, with limited coverage and accuracy. Here we utilize a low-cell number transcriptome based on the Smart-seq2 method to perform long-read sequencing. Our analysis describes additional novel transcripts and complexity of the preimplantation transcriptome, identifying 2280 potential novel transcripts from previously unannotated loci and 6289 novel splicing isoforms from previously annotated genes. Notably, these novel transcripts and isoforms with transcription start sites are enriched for an active promoter modification, H3K4me3. Moreover, we generate a more complete and precise transcriptome by combining long-read and short-read data during early embryogenesis. Based on this approach, we identify a previously undescribed isoform of Kdm4dl with a modified mRNA reading frame and a novel noncoding gene designated XLOC_004958. Depletion of Kdm4dl or XLOC_004958 led to abnormal blastocyst development. Thus, our data provide a high-resolution and more precise transcriptome during preimplantation mouse embryogenesis.

Date: 2020
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DOI: 10.1038/s41467-020-16444-w

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