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

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作者
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
Wenjie Shu
机构
[1] Guangzhou University,Precise Genome Engineering Center, School of Life Sciences
[2] Beijing Institute of Radiation Medicine,Department of Biotechnology
[3] ShanghaiTech University,School of Life Science and Technology
[4] University of Chinese Academy of Sciences,Institute of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology
[5] Chinese Academy of Sciences,Institute of Geriatrics & National Clinical Research Center of Geriatrics Disease
[6] 2nd Medical Center of Chinese PLA General Hospital,Computer School
[7] University of South China,undefined
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摘要
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.
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