GFI1 regulates NK cell maturation and function [scMultiome-seq].

However, the transcriptional mechanisms guiding this process remains incompletely defined. Using paired single cell multiomic profiling, we show that the transcriptional repressor GFI1 epigenetically regulates key molecular programs, including EOMES and T-BET balance, to promote NK cell proliferation and transition from immature to terminally differentiated NK stages.

GFI1 was shown to repress FOXO1 chromatin accessibility in mature NK cells, which normally represses NK cell proliferation and maturation. Co-deletion of both GFI1 and FOXO1 largely rescued NK cell differentiation identifying a critical GFI1-FOXO1 axis essential for protection against tumour metastasis. These findings position GFI1 as an important transcriptional node integrating NK cell differentiation, activation, and effector programming.