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SRX21144999: GSM7659473: IKZF_1; Mus musculus; ATAC-seq
2 ILLUMINA (Illumina NovaSeq 6000) runs: 385.2M spots, 47.4G bases, 16Gb downloads

External Id: GSM7659473_r1
Submitted by: Waterfield, Pediatrics, University of California, San Francisco
Study: Ikaros is a principal regulator of Aire+ mTEC homeostasis, thymic mimetic cell diversity, and central tolerance [Ikaros scATAC-seq]
show Abstracthide Abstract
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. Overall design: scATACseq on sorted EPCAM+ mTECs from conditionally deleted Ikzf1 mice
Sample: IKZF_1
SAMN36698917 • SRS18408250 • All experiments • All runs
Organism: Mus musculus
Library:
Name: GSM7659473
Instrument: Illumina NovaSeq 6000
Strategy: ATAC-seq
Source: GENOMIC
Selection: other
Layout: PAIRED
Construction protocol: Freshly sorted EPCAM+Ly51- mTECs were collected in 0.04% BSA in PBS, then lysed following the Chromium Single Cell ATAC Reagent Kit from 10X Genomics Per UCSF Genomics Core Using chromium single cell ATAC workflow (from 10X Genomics) nuclei were transposed and then encapsulated and barcoded. Libraries were sequenced using NovaSeq 6000 (Illumina)
Runs: 2 runs, 385.2M spots, 47.4G bases, 16Gb
Run# of Spots# of BasesSizePublished
SRR25409051198,342,61924.4G8.1Gb2023-10-25
SRR25409052186,821,03823G7.9Gb2023-10-25

ID:
28580317

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