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A genome-wide screen identifies genes required for erythroid differentiation

Author

Listed:
  • Greggory Myers

    (University of Michigan)

  • Ann Friedman

    (University of Michigan)

  • Lei Yu

    (University of Michigan)

  • Narges Pourmandi

    (University of Michigan
    University of Michigan)

  • Claire Kerpet

    (University of Michigan)

  • Masaki A. Ito

    (University of Michigan)

  • Rilie Saba

    (University of Michigan)

  • Vi Tang

    (Harvard Medical School)

  • Ayse Bilge Ozel

    (University of Michigan)

  • Ingrid L. Bergin

    (University of Michigan)

  • Craig N. Johnson

    (University of Michigan)

  • Chia-Jui Ku

    (University of Michigan)

  • Yu Wang

    (University of Michigan)

  • Ginette Balbin-Cuesta

    (University of Michigan
    University of Michigan)

  • Kim-Chew Lim

    (University of Michigan)

  • Zesen Lin

    (University of Michigan)

  • Claire Drysdale

    (University of Michigan
    University of Michigan)

  • Beth McGee

    (University of Michigan
    University of Michigan)

  • Ryo Kurita

    (Japanese Red Cross Society)

  • Yukio Nakamura

    (RIKEN BioResource Research Center)

  • Xiaofang Liu

    (University of Michigan)

  • David Siemieniak

    (University of Michigan)

  • Sharon A. Singh

    (University of Michigan)

  • Costas A. Lyssiotis

    (University of Michigan
    University of Michigan
    University of Michigan Rogel Cancer Center)

  • Ivan Maillard

    (Memorial Sloan Kettering Cancer Center)

  • Lois S. Weisman

    (University of Michigan
    University of Michigan)

  • James Douglas Engel

    (University of Michigan
    University of Michigan
    University of Michigan Rogel Cancer Center)

  • Rami Khoriaty

    (University of Michigan
    University of Michigan
    University of Michigan
    University of Michigan Rogel Cancer Center)

Abstract

The complete array of genes required for terminal erythroid differentiation remains unknown. To address this knowledge gap, we perform a genome-scale CRISPR knock-out screen in the human erythroid progenitor cell line HUDEP-2 and validate candidate regulators of erythroid differentiation in a custom secondary screen. Comparison of sgRNA abundance in the CRISPR library, proerythroblasts, and orthochromatic erythroblasts, resulted in the identification of genes that are essential for proerythroblast survival and genes that are required for terminal erythroid differentiation. Among the top genes identified are known regulators of erythropoiesis, underscoring the validity of this screen. Notably, using a Log2 fold change of

Suggested Citation

  • Greggory Myers & Ann Friedman & Lei Yu & Narges Pourmandi & Claire Kerpet & Masaki A. Ito & Rilie Saba & Vi Tang & Ayse Bilge Ozel & Ingrid L. Bergin & Craig N. Johnson & Chia-Jui Ku & Yu Wang & Ginet, 2025. "A genome-wide screen identifies genes required for erythroid differentiation," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58739-w
    DOI: 10.1038/s41467-025-58739-w
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    References listed on IDEAS

    as
    1. Kendall R. Sanson & Ruth E. Hanna & Mudra Hegde & Katherine F. Donovan & Christine Strand & Meagan E. Sullender & Emma W. Vaimberg & Amy Goodale & David E. Root & Federica Piccioni & John G. Doench, 2018. "Optimized libraries for CRISPR-Cas9 genetic screens with multiple modalities," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    2. Clare Pacini & Joshua M. Dempster & Isabella Boyle & Emanuel Gonçalves & Hanna Najgebauer & Emre Karakoc & Dieudonne Meer & Andrew Barthorpe & Howard Lightfoot & Patricia Jaaks & James M. McFarland & , 2021. "Integrated cross-study datasets of genetic dependencies in cancer," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    3. Elisa Laurenti & Berthold Göttgens, 2018. "From haematopoietic stem cells to complex differentiation landscapes," Nature, Nature, vol. 553(7689), pages 418-426, January.
    Full references (including those not matched with items on IDEAS)

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