Project description:Foxp3+CD4+ regulatory T cells (Tregs) regulate most types of immune response as well as several processes important for tissue homeostasis – for example, metabolism and repair. Dedicated Treg compartments – with distinct transcriptomes, T-cell-receptor repertoires, and growth/survival factor dependencies – have been identified in several nonlymphoid tissues. These Tregs are specifically adapted to function and operate in their home tissue – when, where and how do they take on their specialized characteristics? We recently reported that a splenic Treg population expressing low levels of the transcription factor, PPARg, contains precursors of Tregs residing in visceral adipose tissue. This finding made sense given that PPARg, the “master-regulator” of adipocyte differentiation, is required for the accumulation and function of Tregs in visceral adipose tissue but not in lymphoid tissues. Here we use single-cell RNA sequencing, single-cell Tcra and Tcrb sequencing, and adoptive-transfer experiments to show that, unexpectedly, the splenic PPARglo Treg population is transcriptionally heterogeneous and engenders Tregs in multiple nonlymphoid tissues beyond visceral adipose tissue, e.g. skin and liver. The existence of a general pool of splenic precursors for nonlymphoid-tissue Tregs opens new possibilities for regulating their emergence experimentally or therapeutically.
Project description:Foxp3+CD4+ regulatory T cells (Tregs) regulate most types of immune response as well as several processes important for tissue homeostasis – for example, metabolism and repair. Dedicated Treg compartments – with distinct transcriptomes, T-cell-receptor repertoires, and growth/survival factor dependencies – have been identified in several nonlymphoid tissues. These Tregs are specifically adapted to function and operate in their home tissue – when, where and how do they take on their specialized characteristics? We recently reported that a splenic Treg population expressing low levels of the transcription factor, PPARg, contains precursors of Tregs residing in visceral adipose tissue. This finding made sense given that PPARg, the “master-regulator” of adipocyte differentiation, is required for the accumulation and function of Tregs in visceral adipose tissue but not in lymphoid tissues. Here we use single-cell RNA sequencing, single-cell Tcra and Tcrb sequencing, and adoptive-transfer experiments to show that, unexpectedly, the splenic PPARglo Treg population is transcriptionally heterogeneous and engenders Tregs in multiple nonlymphoid tissues beyond visceral adipose tissue, e.g. skin and liver. The existence of a general pool of splenic precursors for nonlymphoid-tissue Tregs opens new possibilities for regulating their emergence experimentally or therapeutically.
Project description:Foxp3+CD4+ regulatory T cells (Tregs) regulate most types of immune response as well as several processes important for tissue homeostasis – for example, metabolism and repair. Dedicated Treg compartments – with distinct transcriptomes, T-cell-receptor repertoires, and growth/survival factor dependencies – have been identified in several nonlymphoid tissues. These Tregs are specifically adapted to function and operate in their home tissue – when, where and how do they take on their specialized characteristics? We recently reported that a splenic Treg population expressing low levels of the transcription factor, PPARg, contains precursors of Tregs residing in visceral adipose tissue. This finding made sense given that PPARg, the “master-regulator” of adipocyte differentiation, is required for the accumulation and function of Tregs in visceral adipose tissue but not in lymphoid tissues. Here we use single-cell RNA sequencing, single-cell Tcra and Tcrb sequencing, and adoptive-transfer experiments to show that, unexpectedly, the splenic PPARglo Treg population is transcriptionally heterogeneous and engenders Tregs in multiple nonlymphoid tissues beyond visceral adipose tissue, e.g. skin and liver. The existence of a general pool of splenic precursors for nonlymphoid-tissue Tregs opens new possibilities for regulating their emergence experimentally or therapeutically.
Project description:Robust identification of placental PPARg target genes via mutliple PPARg-dependence criteria. Integration of differential expression data from Pparg-null, Rxra-null, Med1-nul and Ncoa6-null placentas and from WT and Pparg-null Trophoblast stem cells (TSC) differentiated for 2 or 4 days in the presence or absence of the PPARg agonist Rosiglitazone (Rosi).
Project description:Robust identification of placental PPARg target genes via mutliple PPARg-dependence criteria. Integration of differential expression data from Pparg-null, Rxra-null, Med1-nul and Ncoa6-null placentas and from WT and Pparg-null Trophoblast stem cells (TSC) differentiated for 2 or 4 days in the presence or absence of the PPARg agonist Rosiglitazone (Rosi). [Placentas] Three pools of three WT placentas, each vs a litter-matched pool of three Pparg-null placentas Three pools of three WT placentas, each vs a litter-matched pool of three Rxra-null placentas Three pools of three WT placentas, each vs a litter-matched pool of three Med1-null placentas Three pools of three WT placentas, each vs a litter-matched pool of three Ncoa6-null placentas [Trophoblast stem cells (TSC)] Three independent WT TSC lines differentiated for two and four days in the presence or absence of Rosi vs two independent Pparg-null TSC lines differntiated for the same durations in the presence of Rosi