Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptomic analysis of the early effects of sex steroid ablation on BM LT-HSCs 2 days post surgery.

ABSTRACT: Analysis of gene-expression alterations in primitive LT-HSCs as early as 2 days post sex steroid ablation. This study aimed to determine potential intrinsic changes occuring in the LT-HSC population associated with sex steroid ablation (SSA) at a timepoint that preceeded the earliest reported functional hematopoietic enhancements occuring at day 7 post SSA. These results are vital in providing insight into the role of LT-HSCs in initiating SSA-mediated immune regeneration. Total RNA obtained from BM-sorted LT-HSC 2 days after sex steroid ablation compared to sham sex steroid ablation controls.

ORGANISM(S): Mus musculus

SUBMITTER: Danika Khong

PROVIDER: E-GEOD-64841 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Although majority of the genes linked to pediatric cataract exhibit lens fiber cell-enriched expression, our understanding of gene regulation in these cells is limited to function of just eight transcription factors and largely in the context of crystallins. Here, we identify small Maf transcription factors MafG and MafK as regulators of several non-crystallin human cataract genes in fiber cells and establish their significance to cataract. We applied a bioinformatics tool for cataract gene discovery iSyTE to identify MafG and its co-regulators in the lens, and generated various null-allelic combinations of MafG:MafK mouse mutants for phenotypic and molecular analysis. By age 4-months, MafG-/-:MafK+/- mutants exhibit lens defects that progressively develop into cataract. High-resolution phenotypic characterization of MafG-/-:MafK+/- lens reveals severe defects in fiber cells, while microarrays-based expression profiling identifies 97 differentially regulated genes (DRGs). Integrative analysis of MafG-/-:MafK+/- lens-DRGs with 1) binding-motifs and genomic targets of small Mafs and their regulatory partners, 2) iSyTE lens-expression data, and 3) interactions between DRGs in the String database, unravels a detailed small Maf regulatory network in the lens, several nodes of which are linked to human cataract. This analysis prioritizes 36 highly promising candidates from the original 97 DRGs. Significantly, 8/36 (22%) DRGs are associated with cataracts in human (GSTO1, MGST1, SC4MOL, UCHL1) or mouse (Aldh3a1, Crygf, Hspb1, Pcbd1), suggesting a multifactorial etiology that includes elevation of oxidative stress. These data identify MafG and MafK as new cataract-associated candidates and define their function in regulating largely non-crystallin genes linked to mouse and human cataract. Microarray comparision of lenses from mixed background (129Sv/J, C57BL/6J, and ICR) control (MafG+/-:MafK+/-; no-cataract) and compound (MafG-/-:MafK+/-; cataract) mouse mutants

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Transcriptomic analysis of the early effects of sex steroid ablation on BM LT-HSCs 2 days post surgery.

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