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Unraveling the impact of ZZZ3 on the mTOR/ribosome pathway in human embryonic stem cells homeostasis

2024; Elsevier BV; Volume: 19; Issue: 5 Linguagem: Inglês

10.1016/j.stemcr.2024.04.002

2213-6711

Michela Lo Conte, Valeria Lucchino, Stefania Scalise, Clara Zannino, Desirèe Valente, Giada Rossignoli, Maria Stella Murfuni, Chiara Cicconetti, Luana Scaramuzzino, Danilo Swann Matassa, Anna Procopio, Graziano Martello, Giovanni Cuda, Elvira Immacolata Parrotta,

Renal and related cancers

Embryonic stem cells (ESCs) are defined as stem cells with self-renewing and differentiation capabilities. These unique properties are tightly regulated and controlled by complex genetic and molecular mechanisms, whose understanding is essential for both basic and translational research. A large number of studies have mostly focused on understanding the molecular mechanisms governing pluripotency and differentiation of ESCs, while the regulation of proliferation has received comparably less attention. Here, we investigate the role of ZZZ3 (zinc finger ZZ-type containing 3) in human ESCs homeostasis. We found that knockdown of ZZZ3 negatively impacts ribosome biogenesis, translation, and mTOR signaling, leading to a significant reduction in cell proliferation. This process occurs without affecting pluripotency, suggesting that ZZZ3-depleted ESCs enter a "dormant-like" state and that proliferation and pluripotency can be uncoupled also in human ESCs.