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Parallel functional assessment of m6A sites in human endodermal differentiation with base editor screens

Author

Listed:
  • Weisheng Cheng

    (Sun Yat-sen University
    Sun Yat-sen University)

  • Fang Liu

    (the First Affiliated Hospital of Anhui Medical University
    Sun Yat-sen University)

  • Zhijun Ren

    (Sun Yat-sen University
    Sun Yat-sen University)

  • Wenfang Chen

    (Sun Yat-sen University
    Sun Yat-sen University)

  • Yaxin Chen

    (Sun Yat-sen University
    Sun Yat-sen University)

  • Tianwei Liu

    (Sun Yat-sen University
    Sun Yat-sen University)

  • Yixin Ma

    (Sun Yat-sen University
    Sun Yat-sen University)

  • Nan Cao

    (Sun Yat-sen University
    Sun Yat-sen University)

  • Jinkai Wang

    (Sun Yat-sen University
    Sun Yat-sen University
    Sun Yat-sen University)

Abstract

N6-methyladenosine (m6A) plays important role in lineage specifications of embryonic stem cells. However, it is still difficult to systematically dissect the specific m6A sites that are essential for early lineage differentiation. Here, we develop an adenine base editor-based strategy to systematically identify functional m6A sites that control lineage decisions of human embryonic stem cells. We design 7999 sgRNAs targeting 6048 m6A sites to screen for m6A sites that act as either boosters or barriers to definitive endoderm specification of human embryonic stem cells. We identify 78 sgRNAs enriched in the non-definitive endoderm cells and 137 sgRNAs enriched in the definitive endoderm cells. We successfully validate two definitive endoderm promoting m6A sites on SOX2 and SDHAF1 as well as a definitive endoderm inhibiting m6A site on ADM. Our study provides a functional screening of m6A sites and paves the way for functional studies of m6A at individual m6A site level.

Suggested Citation

  • Weisheng Cheng & Fang Liu & Zhijun Ren & Wenfang Chen & Yaxin Chen & Tianwei Liu & Yixin Ma & Nan Cao & Jinkai Wang, 2022. "Parallel functional assessment of m6A sites in human endodermal differentiation with base editor screens," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28106-0
    DOI: 10.1038/s41467-022-28106-0
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    Cited by:

    1. Hongzhi Zeng & Qichen Yuan & Fei Peng & Dacheng Ma & Ananya Lingineni & Kelly Chee & Peretz Gilberd & Emmanuel C. Osikpa & Zheng Sun & Xue Gao, 2023. "A split and inducible adenine base editor for precise in vivo base editing," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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