Histone crotonylation specifically marks the haploid male germ cell gene expression program

BioEssays ◽  
2011 ◽  
Vol 34 (3) ◽  
pp. 187-193 ◽  
Author(s):  
Emilie Montellier ◽  
Sophie Rousseaux ◽  
Yingming Zhao ◽  
Saadi Khochbin
2019 ◽  
Author(s):  
Anuja Sathe ◽  
Sue Grimes ◽  
Billy T. Lau ◽  
Jiamin Chen ◽  
Carlos Suarez ◽  
...  

ABSTRACTPurposeThe tumor microenvironment (TME) consists of a heterogenous cellular milieu that can influence cancer cell behavior. The characteristics of the cellular TME have a dramatic impact on treatments such as immunotherapy. These features can be revealed with single-cell RNA sequencing (scRNA-seq). We hypothesized that single cell gene expression studies of gastric cancer (GC) together with paired normal tissue and peripheral blood mononuclear cells (PBMCs) would identify critical elements of cellular dysregulation not apparent with other approaches.MethodsSingle cell gene expression studies were conducted on seven patients with GC and one patient with intestinal metaplasia. We sequenced 56,167 cells comprising GC (32,407 cells), paired normal tissue (18,657 cells) and PBMCs (5,103 cells). Protein expression of genes of interest was validated by multiplex immunofluorescence.ResultsTumor epithelium had copy number alterations and a distinct gene expression program compared to normal with intra-tumor heterogeneity. The GC TME was significantly enriched for stromal cells, macrophages, dendritic cells (DCs) and Tregs. TME-exclusive stromal cells expressed extracellular matrix components distinct from normal tissue. Macrophages were transcriptionally heterogenous and did not conform to a binary M1/M2 paradigm. Gene expression program of tumor DCs was unique from PBMC DCs. TME-specific cytotoxic T cells comprised of two exhausted heterogenous subsets. Helper, cytotoxic T, Treg and NK cells expressed multiple immune checkpoint or costimulatory molecules. Receptor-ligand analysis revealed TME-exclusive inter-cellular communication.ConclusionsSingle cell gene expression studies revealed widespread reprogramming across multiple cellular elements in the milieu of the GC TME. Cellular remodeling was delineated by changes in cell numbers, transcriptional states and inter-cellular interactions. This characterization facilitates understanding of tumor biology and enables the identification of novel molecular targets including for cancer immunotherapy.STATEMENT OF TRANSLATIONAL RELEVANCEWe leveraged the power of single-cell genomics to characterize the heterogenous cell types and states in the tumor microenvironment (TME). By profiling thousands of single cells from surgical resections of gastric cancer together with paired normal mucosa and peripheral blood mononuclear cells (PBMCs), we determined the deviations in the TME from physiological conditions. Our analysis revealed a cellular reprogramming of the TME compared to normal mucosa in immune and stromal lineages. We detected transcriptional heterogeneity within macrophages and a TME-specific gene expression program in dendritic cells. Cytotoxic T cells in the TME had heterogenous profiles of exhaustion and expression of multiple immune checkpoint and costimulatory molecules. We constructed a receptor-ligand based inter-cellular communications network that was exclusive to tumor tissue. These discoveries provide information at a highly granular cellular resolution enabling advances in cancer biology, biomarker discovery and identification of treatment targets such as for immunotherapy.


Immunity ◽  
2002 ◽  
Vol 17 (1) ◽  
pp. 51-62 ◽  
Author(s):  
A.L. Shaffer ◽  
Kuo-I Lin ◽  
Tracy C. Kuo ◽  
Xin Yu ◽  
Elaine M. Hurt ◽  
...  

2010 ◽  
Vol 40 (8) ◽  
pp. 2143-2154 ◽  
Author(s):  
Philippe Kastner ◽  
Susan Chan ◽  
Walter K. Vogel ◽  
Ling-Juan Zhang ◽  
Acharawan Topark-Ngarm ◽  
...  

Leukemia ◽  
2018 ◽  
Vol 32 (8) ◽  
pp. 1865-1868 ◽  
Author(s):  
Csaba Mahotka ◽  
Sanil Bhatia ◽  
Jutta Kollet ◽  
Edgar Grinstein

2018 ◽  
Vol 20 (4) ◽  
pp. 245-255 ◽  
Author(s):  
Maryam Gholamitabar Tabari ◽  
Seyed Gholam Ali Jorsaraei ◽  
Mohammad Ghasemzadeh-Hasankolaei ◽  
Ali Asghar Ahmadi ◽  
Mehdi Amirikia

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Jenny N. Poynter ◽  
Jessica R. B. M. Bestrashniy ◽  
Kevin A. T. Silverstein ◽  
Anthony J. Hooten ◽  
Christopher Lees ◽  
...  

2019 ◽  
Vol 5 (8) ◽  
pp. eaaw0706 ◽  
Author(s):  
Syed Nurul Hasan ◽  
Amit Sharma ◽  
Sayantani Ghosh ◽  
Sung-Wook Hong ◽  
Sinchita Roy-Chowdhuri ◽  
...  

Foxp3 and its protein partners establish a regulatory T (Treg) cell transcription profile and promote immunological tolerance. However, molecular features contributing to a Treg-specific gene expression program are still incompletely understood. We find that the transcription factor Bcl11b is a prominent Foxp3 cofactor with multifaceted functions in Treg biology. Optimal genomic recruitment of Foxp3 and Bcl11b is critically interdependent. Genome-wide occupancy studies coupled with gene expression profiling reveal that Bcl11b, in association with Foxp3, is primarily responsible in establishing a Treg-specific gene activation program. Furthermore, Bcl11b restricts misdirected recruitment of Foxp3 to sites, which would otherwise result in an altered Treg transcriptome profile. Consequently, Treg-specific ablation of Bcl11b results in marked breakdown of immune tolerance, leading to aggressive systemic autoimmunity. Our study provides previously underappreciated mechanistic insights into molecular events contributing to basic aspects of Treg function. Furthermore, it establishes a therapeutic target with potential implications in autoimmunity and cancer.


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