scholarly journals B-Cell and Monocyte Contribution to Systemic Lupus Erythematosus Identified by Cell-Type-Specific Differential Expression Analysis in RNA-Seq Data

2015 ◽  
Vol 9s3 ◽  
pp. BBI.S29470 ◽  
Author(s):  
Mikhail G. Dozmorov ◽  
Nicolas Dominguez ◽  
Krista Bean ◽  
Susan R. Macwana ◽  
Virginia Roberts ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Differential Expression ◽  
Expression Analysis ◽  
Lupus Erythematosus ◽  
Differential Expression Analysis ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Gene Expression ◽  
Cell Type Specific

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by complex interplay among immune cell types. SLE activity is experimentally assessed by several blood tests, including gene expression profiling of heterogeneous populations of cells in peripheral blood. To better understand the contribution of different cell types in SLE pathogenesis, we applied the two methods in cell-type-specific differential expression analysis, csSAM and DSection, to identify cell-type-specific gene expression differences in heterogeneous gene expression measures obtained using RNA-seq technology. We identified B-cell-, monocyte-, and neutrophil-specific gene expression differences. Immunoglobulin-coding gene expression was altered in B-cells, while a ribosomal signature was prominent in monocytes. On the contrary, genes differentially expressed in the heterogeneous mixture of cells did not show any functional enrichment. Our results identify antigen binding and structural constituents of ribosomes as functions altered by B-cell- and monocyte-specific gene expression differences, respectively. Finally, these results position both csSAM and DSection methods as viable techniques for cell-type-specific differential expression analysis, which may help uncover pathogenic, cell-type-specific processes in SLE.

scholarly journals Cell type specific gene expression analysis of prostate needle biopsies resolves tumor tissue heterogeneity

Oncotarget ◽  
2014 ◽  
Vol 6 (2) ◽  
pp. 1302-1314 ◽  
Author(s):  
Malte Krönig ◽  
Max Walter ◽  
Vanessa Drendel ◽  
Martin Werner ◽  
Cordula A. Jilg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Tumor Tissue ◽  
Specific Gene ◽  
Cell Type ◽  
Tissue Heterogeneity ◽  
Specific Gene Expression ◽  
Cell Type Specific

scholarly journals Srf destabilizes cellular identity by suppressing cell-type-specific gene expression programs

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Takashi Ikeda ◽  
Takafusa Hikichi ◽  
Hisashi Miura ◽  
Hirofumi Shibata ◽  
Kanae Mitsunaga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Gene Expression ◽  
Cell Type Specific ◽  
Cellular Identity

scholarly journals Distinct CoREST complexes act in a cell-type-specific manner

2019 ◽  
Author(s):  
Igor Mačinković ◽  
Ina Theofel ◽  
Tim Hundertmark ◽  
Kristina Kovač ◽  
Stephan Awe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Germ Line ◽  
Protein Complexes ◽  
Specific Gene ◽  
S2 Cells ◽  
Cell Type ◽  
Specific Gene Expression ◽  
Genome Wide ◽  
A Cell ◽  
Cell Type Specific

Abstract CoREST has been identified as a subunit of several protein complexes that generate transcriptionally repressive chromatin structures during development. However, a comprehensive analysis of the CoREST interactome has not been carried out. We use proteomic approaches to define the interactomes of two dCoREST isoforms, dCoREST-L and dCoREST-M, in Drosophila. We identify three distinct histone deacetylase complexes built around a common dCoREST/dRPD3 core: A dLSD1/dCoREST complex, the LINT complex and a dG9a/dCoREST complex. The latter two complexes can incorporate both dCoREST isoforms. By contrast, the dLSD1/dCoREST complex exclusively assembles with the dCoREST-L isoform. Genome-wide studies show that the three dCoREST complexes associate with chromatin predominantly at promoters. Transcriptome analyses in S2 cells and testes reveal that different cell lineages utilize distinct dCoREST complexes to maintain cell-type-specific gene expression programmes: In macrophage-like S2 cells, LINT represses germ line-related genes whereas other dCoREST complexes are largely dispensable. By contrast, in testes, the dLSD1/dCoREST complex prevents transcription of germ line-inappropriate genes and is essential for spermatogenesis and fertility, whereas depletion of other dCoREST complexes has no effect. Our study uncovers three distinct dCoREST complexes that function in a lineage-restricted fashion to repress specific sets of genes thereby maintaining cell-type-specific gene expression programmes.

scholarly journals Dynamic changes in cis-regulatory occupancy by Six1 and its cooperative interactions with distinct cofactors drive lineage-specific gene expression programs during progressive differentiation of the auditory sensory epithelium

2020 ◽  
Vol 48 (6) ◽  
pp. 2880-2896 ◽  
Author(s):  
Jun Li ◽  
Ting Zhang ◽  
Aarthi Ramakrishnan ◽  
Bernd Fritzsch ◽  
Jinshu Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Elements ◽  
Sensory Epithelium ◽  
Hair Bundle ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Gene Expression ◽  
Wide Range ◽  
Cell Type Specific ◽  
Lineage Specific Gene

Abstract The transcription factor Six1 is essential for induction of sensory cell fate and formation of auditory sensory epithelium, but how it activates gene expression programs to generate distinct cell-types remains unknown. Here, we perform genome-wide characterization of Six1 binding at different stages of auditory sensory epithelium development and find that Six1-binding to cis-regulatory elements changes dramatically at cell-state transitions. Intriguingly, Six1 pre-occupies enhancers of cell-type-specific regulators and effectors before their expression. We demonstrate in-vivo cell-type-specific activity of Six1-bound novel enhancers of Pbx1, Fgf8, Dusp6, Vangl2, the hair-cell master regulator Atoh1 and a cascade of Atoh1’s downstream factors, including Pou4f3 and Gfi1. A subset of Six1-bound sites carry consensus-sequences for its downstream factors, including Atoh1, Gfi1, Pou4f3, Gata3 and Pbx1, all of which physically interact with Six1. Motif analysis identifies RFX/X-box as one of the most significantly enriched motifs in Six1-bound sites, and we demonstrate that Six1-RFX proteins cooperatively regulate gene expression through binding to SIX:RFX-motifs. Six1 targets a wide range of hair-bundle regulators and late Six1 deletion disrupts hair-bundle polarity. This study provides a mechanistic understanding of how Six1 cooperates with distinct cofactors in feedforward loops to control lineage-specific gene expression programs during progressive differentiation of the auditory sensory epithelium.

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