A genome-wide screen identifies genes required for erythroid differentiation

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, Ginette Balbin-Cuesta, Kim-Chew Lim, Zesen Lin, Claire Drysdale, Beth McGee, Ryo Kurita, Yukio Nakamura, Xiaofang Liu, David Siemieniak, Sharon A. Singh, Costas A. Lyssiotis, Ivan Maillard, Lois S. Weisman, James Douglas Engel and Rami Khoriaty ()
Additional contact information
Greggory Myers: University of Michigan
Ann Friedman: University of Michigan
Lei Yu: University of Michigan
Narges Pourmandi: 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
Kim-Chew Lim: University of Michigan
Zesen Lin: University of Michigan
Claire Drysdale: University of Michigan
Beth McGee: 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
Ivan Maillard: Memorial Sloan Kettering Cancer Center
Lois S. Weisman: University of Michigan
James Douglas Engel: University of Michigan
Rami Khoriaty: University of Michigan

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: 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

Date: 2025
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DOI: 10.1038/s41467-025-58739-w

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