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Ikaros is a principal regulator of Aire+ mTEC homeostasis, thymic mimetic cell diversity, and central tolerance [Ikaros scATAC-seq]

ABSTRACT: Ikaros is a principal regulator of Aire+ mTEC homeostasis, thymic mimetic cell diversity, and central tolerance [Ikaros scATAC-seq]

PROVIDER: PRJNA998054 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25409049_1.fastq.gz	Fastqsanger.gz
	SRR25409049_2.fastq.gz	Fastqsanger.gz
	SRR25409050_1.fastq.gz	Fastqsanger.gz
	SRR25409050_2.fastq.gz	Fastqsanger.gz
	SRR25409051_1.fastq.gz	Fastqsanger.gz

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Ikaros is a principal regulator of Aire+ mTEC homeostasis, thymic mimetic cell diversity, and central tolerance [Ikaros scATAC-seq]

Project description:The zinc-finger transcription factor Ikaros (Ikzf1) modulates key gene expression programs important for hematopoietic development, and coding mutations in IKZF1 are found in patients with immunodeficiency, leukemia, and autoimmunity. While Ikaros has a well-established function in hematopoiesis, its role in other cell types is less well defined. Here, we uncover new functions for Ikaros in thymic epithelial lineage development and show that Ikzf1 expression in medullary thymic epithelial cells (mTECs) is required for both Autoimmune Regulator positive (Aire+) mTEC development and tissue-specific antigen (TSA) gene expression. Accordingly, TEC-specific deletion of Ikzf1 in mice results in a profound decrease in Aire+ mTECs, a global loss of TSA gene expression, and the development of autoimmunity. Moreover, Ikaros shapes thymic mimetic cell diversity and its deletion results in a dramatic expansion of thymic tuft cells and muscle-like mTECs and a loss of other Aire-dependent mimetic populations. Single-cell analysis reveals Ikaros modulates core transcriptional programs in TECs that correlate with the observed cellular changes. Our findings highlight a previously undescribed role for Ikaros in regulating epithelial lineage development and function, and suggest that failed thymic central tolerance could contribute to the autoimmunity seen in humans with IKZF1 mutations.

2023-10-25 | GSE238149 | GEO

Ikaros is a principal regulator of Aire+ mTEC homeostasis, thymic mimetic cell diversity, and central tolerance (scRNA seq)

2023-10-25 | GSE241742 | GEO

Ikaros is a principal regulator of Aire+ mTEC homeostasis, thymic mimetic cell diversity, and central tolerance [Pou2f3 RNA-seq]

2023-10-25 | GSE238148 | GEO

Ikaros is a principal regulator of Aire+ mTEC homeostasis, thymic mimetic cell diversity, and central tolerance [Tuft cell RNA-seq]

2023-10-25 | GSE237988 | GEO

Ikaros is a principal regulator of Aire+ mTEC homeostasis, thymic mimetic cell diversity, and central tolerance

Project description:Ikaros is a principal regulator of Aire+ mTEC homeostasis, thymic mimetic cell diversity, and central tolerance

| PRJNA998049 | ENA

Ikaros is a principal regulator of Aire+ mTEC homeostasis, thymic mimetic cell diversity, and central tolerance (scRNA seq)

Project description:Ikaros is a principal regulator of Aire+ mTEC homeostasis, thymic mimetic cell diversity, and central tolerance (scRNA seq)

| PRJNA1009446 | ENA

Ikaros is a principal regulator of Aire+ mTEC homeostasis, thymic mimetic cell diversity, and central tolerance [Pou2f3 RNA-seq]

Project description:Ikaros is a principal regulator of Aire+ mTEC homeostasis, thymic mimetic cell diversity, and central tolerance [Pou2f3 RNA-seq]

| PRJNA998052 | ENA

Ikaros is a principal regulator of Aire+ mTEC homeostasis, thymic mimetic cell diversity, and central tolerance [Tuft cell RNA-seq]

Project description:Ikaros is a principal regulator of Aire+ mTEC homeostasis, thymic mimetic cell diversity, and central tolerance [Tuft cell RNA-seq]

| PRJNA997348 | ENA

RNA-seq of medullary thymic epithelial cell (mTEC) subsets in inducible Aire-lineage tracing mice

Project description:The goal of the study was to sequence mRNA expression from sorted medullary thymic epithelial cell (mTEC) subsets in inducible Aire-CreERT2.R26-Stopfl-tdTomato lineage tracing mice after a pulse chase. Four cell subsets were sorted 7 days after a single 2mg pulse of tamoxifen administered by oral gavage. 4 biological replicates (1,2,3,4) were collected derived from 12 pooled thymi per replicate. From the DAPI-;CD45-;EpCAM+ TEC pool, cells were sorted as: pre-Aire (MHCIIlo;RFP-), early-Aire (MHCIIhi;RFP-), late-Aire (MHCIIhi;RFP+), and post-Aire (MHCIIlo;RFP+). The data were used to identify differentially expressed genes across the four mTEC subsets to examine mTEC heterogeneity and identify novel mTEC subpopulations.

2018-05-19 | GSE114651 | GEO

GIM mTEC Aire silencing

Project description:We used the TriFectaTM (IDT, Integrated DNA Technologies, Coralville, IA, USA) anti-Aire RNAi sequence (GGAUUCUCUUUAAGGACUACAAUCTAGAUUGUAGUCCUUAAAGAGAAUCCUC) in order to silencing Aire mRNA. Confluent cultures of 3.10 mTEC cell line were transfected with 10nM of anti-Aire siRNA using Hiperfect reagent (Qiagen, GmbH, Hilden, Germany) following manufacturerM-^Rs instructions. After transfection, cells were cultured during 24 h in RPMI medium as above mentioned and total RNA was extracted using the mirVana kitM-. (Ambion, Austin, TX, USA), which served as template for cDNA synthesis. Gene knockdown was confirmed by quantitative reverse transcription PCR (qRT-PCR) using the primers 5_-GCAACTCTGGCCTCAAAGAG-3_ forward and 5_-GGTCTGAATTCCGTTTCCAA-3_ reverse, which allowed amplification of a 120 bp PCR product corresponding to a segment of the Aire cDNA. The cDNA samples were prepared using Superscript II reverse transcriptase (Invitrogen Corporation, Carlsbad, CA, USA) enzyme, as recommended. Expression of the above mentioned genes was quantified using a 7500 Real Time PCR System (Applied Biosystems)

2011-08-31 | E-MEXP-3213 | biostudies-arrayexpress

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