As part of my PhD project, we investigated the 3D genome organization of murine T cells, focusing on roles of SATB1 and CTCF. Our work was published @NatureComms and our optimized HiChIP and Hi-C protocol in @MPs_MDPI 🧵👇.1/n.

RT @czexpats: 🚨 Our conference on academic culture is just around the corner! 🚨. What do top researchers need from their institutions? How….

RT @WJGreenleaf: Our work using single-molecule chromatin configurations to link TF binding to gene expression is now out on bioRxiv! Amazi….

RT @anshulkundaje: Great paper. I strongly agree that causal gene regulatory network inference (i.e. where u can actually claim gene A caus….

RT @NatureComms: Researchers @zelenkt @BabiSpilianakis part of @IMBB_FORTH @MSCActions @Mariecurie_alum show SATB1, a predominantly T-cell….

This work was led by Eric Helm and @dorina_avram @MoffittNews . However, it would not be possible without help of our numerous collaborators including Bryceson's lab, Conejo-Garcia's lab, @gatechatl @Zhang_Lab_UFL @akwiatkowski @keselowsky @BSheridanLab and many others. 18/.

Please join my poster presentation P321 on this topic today 5-14-2023 at 2:30pm at #AAI2023 @ImmunologyAAI.17/.

Additionally, several NK receptors, including CD56, CD161 (KLRB1), CD117 and NKP46/NCR1, were upregulated in BCL11B-deficient human Trm-like cells, suggesting a common role of BCL11B in mice and humans. 16/.

Depletion of BCL11B in ex vivo differentiated human Trm-like CD8+ T cells resulted in upregulation of several residency program proteins, including CD69 and CD49a and downregulation of CD62L and CCR7, part of the Trm cell program. 15/.

CRISPR-mediated removal of Ahr and Prdm1 in Trm-like cells indicated that Bcl11b restricts Trm cell differentiation through control of both Ahr and Prdm1. 14/.

Placing mice on Ahr ligand-deficient diet (AIN-76a) to block its activity, we examined the relevance of Ahr elevation in KO Trm precursor cells. Absence of diet derived Ahr ligands normalized KO/WT ratio in the intestine, while the frequencies in the spleen remained unaltered.13/.

We focused on the factor Ahr as an emerging upstream regulator of the effector Trm program. In line with the motif enrichment analysis, Ahr ChIP-seq peaks were enriched at Bcl11b-bound gene promoters and regions with decreased chromatin accessibility in the KO. #Ahr.12/.

The effector genes such as Prdm1 (encoding Blimp1) and granzymes were all upregulated in Bcl11b-dependent manner, together with NK and myeloid genes, which were consistently upregulated in all tested CD8+ T cell subsets. #Prdm1.11/.

Forced expression of Tcf7 rescued the phenotype and normalized the WT/KO ratio of Trm precursor cells within the small intestine. 10/.

The Tcf7 locus itself was highly occupied by Bcl11b suggesting a direct regulation by Bcl11b. However, Bcl11b also bound and possibly positively regulated other targets from the stem-like program such as Id3 and tissue residency program genes including Klf2, S1pr1 and Ccr7. 9/.

Signature transcription factor of the stem-like program Tcf1 was enriched at promoters bound by Bcl11b and at peaks with decreased chromatin accessibility. The latter was also in line with unbiased motif enrichment analysis of differential ATAC-seq and H3K27ac peaks. 8/.

Transcriptional changes were in line with changes in epigenetic status determined by ATAC-seq, H3K27ac ChIP-seq and H3K4me3 CUT&RUN. 7/.

Particularly the Bcl11b-deficient Trm cells had vastly deregulated transcription programs, specifically genes from the stem-like program were mostly downregulated while effector program genes upregulated. #Tcf1 #Tcf7 #stemness #effectorTcells.6/.

Despite the accumulation of Bcl11b-deficient Trm cells in the gut, they were less effective in bacterial clearance following re-infection. 5/.

On the other hand, Bcl11b-deficient Trm cells (CD69+CD103+) accumulated in the small intestine and this deregulation was long-lasting, present even after 90 days post-infection. 4/.