Differentiation Stage-Specific Use of Cap-Independent and Cap-Dependent Translation Initiation in Hematopoiesis

September 2025

Michael Mazzola, Ting Zhao, Anna Kiem, Trine Kristiansen, Karin Gustafsson, Lai Ping Wong, Emily Scott-Solomon, Marissa Fahlberg, Sarah Forward, Emane Rose Assita, Giulia Schiroli, Maris Handley, Youmna Kfoury, Tsuyoshi Fukushima, Samuel D. Keyes, Azeem Sharda, Jelena Milosevic, Hiroki Kato, Pavel Ivanov, David B. Sykes, Sheldon J. J. Kwok, Ruslan I. Sadreyev, Vijay G. Sankaran, Ya‐Chieh Hsu, David T Scadden

cap-independent translation cap-dependent translation IRES-mediated translation hair follicles hematopoiesis epithelial differentiation PTBP1 RNA processing protein

TLDR Low IRES/Cap translation is linked to higher stem cell potential.

The study investigates the role of cap-independent, IRES-mediated translation initiation relative to cap-dependent translation (IRES/Cap) in hematopoiesis and epithelial differentiation, including hair follicles. Using an IRES/Cap reporter mouse, researchers found that caloric stress increased IRES/Cap translation across differentiation states. Surprisingly, IRES/Cap also increased during normal differentiation in hematopoietic and epithelial cells, independent of protein output or cell cycle. Cells with lower IRES utilization exhibited higher multipotent capability in vivo, indicating that low IRES/Cap is associated with high stemness. The RNA processing protein PTBP1 mediates this translation initiation preference, suggesting that modulation of translation initiation is involved in cell differentiation.

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Differentiation Stage-Specific Use of Cap-Independent and Cap-Dependent Translation Initiation in Hematopoiesis

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research Emerging Roles of Transit-Amplifying Cells in Tissue Regeneration and Cancer

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