Loss of PBAF Promotes Effector Differentiation and Limits CD8+ T Cell Exhaustion in Chronic Viral Infection and Cancer [multiomics]

To gain insights into how PBAF complex regulates dynamic chromatin structure changes in LCMV-specific CD8+ T cells during chronic viral infection and examine the how PBAF-deficiency alters the transcriptional and epigenetic heterogeneity of CD8+ T cells, we performed single cell RNA + ATAC multiomic sequencing on Arid2- and Pbrm1-deficient CD8+ T cells and their wild-type counterpart. Overall design: Naive P14 CD8 T cells isolated from mouse spleens were transfected with CRISPR ribonucleoprotein (RNP) to knock out Pbrm1 (sgPbrm1) or Arid2 (sgArid2). 2500 transfected CD45.1+ P14 T cells were transferred to CD45.1- C57BL/6 mice followed by LCMV Clone 13 infection. P14 T cells were FACS-sorted from spleens on day 21 p.i. and extracted nuclei were used for 10x single cell RNA+ATAC-seq library construction following the 10x protocol.