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Inhibition of farnesyltransferase activity diminishes hematopoietic stem cell ex vivo expansion ability

Newman, C.; Alves, I. M.; Hagen, M. W.; Wellington, R.; Hadland, B. K.; Quintana, A. M.; Termini, C. M.

2025-10-31 cell biology
10.1101/2025.10.30.685582 bioRxiv
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ABSTRACT/SUMMARYThe rationale underlying this work is that elucidating the contribution of farnesyltransferase activity to hematopoietic stem cell expansion ex vivo will provide knowledge needed to better support hematopoietic stem cell expansion techniques for clinical applications that rely on this approach, like hematopoietic cell transplants and gene therapy. We discovered that pharmacological inhibition of farnesyltransferase activity with lonafarnib substantially diminished the ex vivo expansion potential of human and mouse hematopoietic stem cells, highlighting that hematopoietic stem cells rely on isoprenoids for their ex vivo maintenance.

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