Ing4-deficiency enhances HSC quiescence and confers resistance to inflammatory stress [article]

Zanshé Thompson, Georgina A. Anderson, Melanie Rodriguez, Seth Gabriel, Vera Binder, Alison M. Taylor, Katie L. Kathrein
2021 bioRxiv   pre-print
Hematopoiesis is tightly regulated by a network of transcription factors and complexes that are required for the development and maintenance of hematopoietic stem cells (HSCs). We recently identified the tumor suppressor, Ing4, as a critical regulator of HSC homeostasis. Though the Ing4 mechanism of action remains poorly characterized, it has been shown to promote stem-like cell characteristics in malignant cells. This activity is, in part, due to Ing4 mediated regulation of several major
more » ... ing pathways, including NF-kB and c-Myc. In murine hematopoiesis, Ing4 deficiency induces G0 arrest in HSCs, while simultaneously promoting gene expression signatures associated with differentiation. This results in a poised state for Ing4-deficient HSCs. Long term HSCs are unable to overcome this block, but short-term HSCs convert the poised state into regenerative capacity during hematopoietic challenges, including irradiation and transplantation. Overall, our findings suggest that Ing4 plays a crucial role in the regulation of hematopoiesis. Our model provides key tools for further identification and characterization of pathways that control quiescence and differentiation in HSCs.
doi:10.1101/2021.07.14.452366 fatcat:4wm3tgvm7fbp7hjnuh2444je5q