Special AT-rich Sequence-Binding Protein 1 (SATB1) is a lineage specific transcription regulator
which plays a pivotal role in orchestrating the spatiotemporal development of T cells. Although it
is known that SATB1 deletion is associated with autoimmunity, the precise mechanisms
underlying this phenotype are poorly understood. In this study we investigate the drivers of the
autoimmunity that SATB1 deletion causes and how it is reversed upon simultaneous deletion of
SATB1 and Bach1. We performed single cell transcriptomic analysis, and identified a newly
formed cluster, characterized by the expression of cMaf. Furthermore, using an array of
bioinformatic tools we discovered that this unique cluster exhibits an activated phenotype,
seemingly regulated by cMaf. Additionally, immunofluorescence experiments unveiled disrupted
spleen morphology in SATB1-depleted animals, a disruption absent in animals with combined
SATB1 and Bach1 depletion. Altogether, our findings highlight cMaf a mediator of autoimmunity,
and strengthen the notion that double SATB1 and BACH1 depletion rescues the autoimmune
phenotype.
(EL)
Special AT-rich Sequence-Binding Protein 1 (SATB1) is a lineage specific transcription regulator
which plays a pivotal role in orchestrating the spatiotemporal development of T cells. Although it
is known that SATB1 deletion is associated with autoimmunity, the precise mechanisms
underlying this phenotype are poorly understood. In this study we investigate the drivers of the
autoimmunity that SATB1 deletion causes and how it is reversed upon simultaneous deletion of
SATB1 and Bach1. We performed single cell transcriptomic analysis, and identified a newly
formed cluster, characterized by the expression of cMaf. Furthermore, using an array of
bioinformatic tools we discovered that this unique cluster exhibits an activated phenotype,
seemingly regulated by cMaf. Additionally, immunofluorescence experiments unveiled disrupted
spleen morphology in SATB1-depleted animals, a disruption absent in animals with combined
SATB1 and Bach1 depletion. Altogether, our findings highlight cMaf a mediator of autoimmunity,
and strengthen the notion that double SATB1 and BACH1 depletion rescues the autoimmune
phenotype.
(EN)
University of Crete
