scholarly journals Putative Multifunctional Signature of Lung Metastases in Dedifferentiated Chondrosarcoma

Sarcoma ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Sergey Malchenko ◽  
Elisabeth A. Seftor ◽  
Yuri Nikolsky ◽  
Susan L. Hasegawa ◽  
Sean Kuo ◽  
...  

Chondrosarcomas are among the most malignant skeletal tumors. Dedifferentiated chondrosarcoma is a highly aggressive subtype of chondrosarcoma, with lung metastases developing within a few months of diagnosis in 90% of patients. In this paper we performed comparative analyses of the transcriptomes of five individual metastatic lung lesions that were surgically resected from a patient with dedifferentiated chondrosarcoma. We document for the first time a high heterogeneity of gene expression profiles among the individual lung metastases. Moreover, we reveal a signature of “multifunctional” genes that are expressed in all metastatic lung lesions. Also, for the first time, we document the occurrence of massive macrophage infiltration in dedifferentiated chondrosarcoma lung metastases.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bing He ◽  
Ping Chen ◽  
Sonia Zambrano ◽  
Dina Dabaghie ◽  
Yizhou Hu ◽  
...  

AbstractMolecular characterization of the individual cell types in human kidney as well as model organisms are critical in defining organ function and understanding translational aspects of biomedical research. Previous studies have uncovered gene expression profiles of several kidney glomerular cell types, however, important cells, including mesangial (MCs) and glomerular parietal epithelial cells (PECs), are missing or incompletely described, and a systematic comparison between mouse and human kidney is lacking. To this end, we use Smart-seq2 to profile 4332 individual glomerulus-associated cells isolated from human living donor renal biopsies and mouse kidney. The analysis reveals genetic programs for all four glomerular cell types (podocytes, glomerular endothelial cells, MCs and PECs) as well as rare glomerulus-associated macula densa cells. Importantly, we detect heterogeneity in glomerulus-associated Pdgfrb-expressing cells, including bona fide intraglomerular MCs with the functionally active phagocytic molecular machinery, as well as a unique mural cell type located in the central stalk region of the glomerulus tuft. Furthermore, we observe remarkable species differences in the individual gene expression profiles of defined glomerular cell types that highlight translational challenges in the field and provide a guide to design translational studies.


2008 ◽  
Vol 3 ◽  
pp. BMI.S590 ◽  
Author(s):  
Han-Jin Park ◽  
Jung Hwa Oh ◽  
Seokjoo Yoon ◽  
S.V.S. Rana

Benzene is used as a general purpose solvent. Benzene metabolism starts from phenol and ends with p-benzoquinone and o-benzoquinone. Liver injury inducted by benzene still remains a toxicologic problem. Tumor related genes and immune responsive genes have been studied in patients suffering from benzene exposure. However, gene expression profiles and pathways related to its hepatotoxicity are not known. This study reports the results obtained in the liver of BALB/C mice (SLC, Inc., Japan) administered 0.05 ml/100 g body weight of 2% benzene for six days. Serum, ALT, AST and ALP were determined using automated analyzer (Fuji., Japan). Histopathological observations were made to support gene expression data. c-DNA microarray analyses were performed using Affymetrix Gene-chip system. After six days of benzene exposure, twenty five genes were down regulated whereas nineteen genes were up-regulated. These gene expression changes were found to be related to pathways of biotransformation, detoxification, apoptosis, oxidative stress and cell cycle. It has been shown for the first time that genes corresponding to circadian rhythms are affected by benzene. Results suggest that gene expression profile might serve as potential biomarkers of hepatotoxicity during benzene exposure.


2020 ◽  
Vol 21 (3) ◽  
pp. 861 ◽  
Author(s):  
Yingdan Yuan ◽  
Bo Zhang ◽  
Xinggang Tang ◽  
Jinchi Zhang ◽  
Jie Lin

Dendrobium is widely used in traditional Chinese medicine, which contains many kinds of active ingredients. In recent years, many Dendrobium transcriptomes have been sequenced. Hence, weighted gene co-expression network analysis (WGCNA) was used with the gene expression profiles of active ingredients to identify the modules and genes that may associate with particular species and tissues. Three kinds of Dendrobium species and three tissues were sampled for RNA-seq to generate a high-quality, full-length transcriptome database. Based on significant changes in gene expression, we constructed co-expression networks and revealed 19 gene modules. Among them, four modules with properties correlating to active ingredients regulation and biosynthesis, and several hub genes were selected for further functional investigation. This is the first time the WGCNA method has been used to analyze Dendrobium transcriptome data. Further excavation of the gene module information will help us to further study the role and significance of key genes, key signaling pathways, and regulatory mechanisms between genes on the occurrence and development of medicinal components of Dendrobium.


2020 ◽  
Vol 32 (11) ◽  
pp. 709-717 ◽  
Author(s):  
Lukas Amann ◽  
Marco Prinz

Abstract The field of macrophage biology has made enormous progress over recent years. This was triggered by the advent of several new techniques such as the establishment of Cre/loxP-based transgenic mouse models that allowed for the first time delineation of the ontogeny and function of specific macrophage populations across many tissues. In addition, the introduction of new high-throughput technologies like bulk RNA sequencing and later single-cell RNA sequencing as well as advances in epigenetic analysis have helped to establish gene expression profiles, enhancer landscapes and local signaling cues that define and shape the identity of diverse macrophage populations. Nonetheless, some macrophage populations, like the ones residing in the peripheral nervous system (PNS), have not been studied in such detail yet. Here, we discuss recent studies that shed new light on the ontogeny, heterogeneity and gene expression profiles of resident macrophages in peripheral nerves and described differential activation of macrophage subsets during and after acute sciatic nerve injury.


Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 812 ◽  
Author(s):  
Paranita Ferronika ◽  
Joost Hof ◽  
Gursah Kats-Ugurlu ◽  
Rolf H. Sijmons ◽  
Martijn M. Terpstra ◽  
...  

While intratumour genetic heterogeneity of primary clear cell renal cell carcinoma (ccRCC) is well characterized, the genomic profiles of metastatic ccRCCs are seldom studied. We profiled the genomes and transcriptomes of a primary tumour and matched metastases to better understand the evolutionary processes that lead to metastasis. In one ccRCC patient, four regions of the primary tumour, one region of the thrombus in the inferior vena cava, and four lung metastases (including one taken after pegylated (PEG)-interferon therapy) were analysed separately. Each sample was analysed for copy number alterations and somatic mutations by whole exome sequencing. We also evaluated gene expression profiles for this patient and 15 primary tumour and 15 metastasis samples from four additional patients. Copy number profiles of the index patient showed two distinct subgroups: one consisted of three primary tumours with relatively minor copy number changes, the other of a primary tumour, the thrombus, and the lung metastases, all with a similar copy number pattern and tetraploid-like characteristics. Somatic mutation profiles indicated parallel clonal evolution with similar numbers of private mutations in each primary tumour and metastatic sample. Expression profiling of the five patients revealed significantly changed expression levels of 57 genes between primary tumours and metastases, with enrichment in the extracellular matrix cluster. The copy number profiles suggest a punctuated evolution from a subregion of the primary tumour. This process, which differentiated the metastases from the primary tumours, most likely occurred rapidly, possibly even before metastasis formation. The evolutionary patterns we deduced from the genomic alterations were also reflected in the gene expression profiles.


Blood ◽  
2016 ◽  
Vol 127 (15) ◽  
pp. 1896-1906 ◽  
Author(s):  
Bruno Paiva ◽  
Luis A. Corchete ◽  
Maria-Belen Vidriales ◽  
Noemi Puig ◽  
Patricia Maiso ◽  
...  

Key Points We report for the first time the biological features of MRD cells in MM and unravel that clonal selection is already present at the MRD stage. MRD cells show a singular phenotypic signature that may result from persisting clones with different genetic and gene expression profiles.


2014 ◽  
Author(s):  
Simone Ecker ◽  
Vera Pancaldi ◽  
Daniel Rico ◽  
Alfonso Valencia

Background: Chronic Lymphocytic Leukemia (CLL) presents two subtypes which have drastically different clinical outcomes. So far, these two subtypes are not associated to clear differences in gene expression profiles. Interestingly, recent results have highlighted important roles for heterogeneity, both at the genetic and at the epigenetic level in CLL progression. Results: We propose to use gene expression variability across patients to investigate differences between the two CLL subtypes. We find that the most aggressive type of this disease shows higher variability of gene expression across patients and we elaborate on this observation to produce a method that classifies patients into clinical subtypes. Finally, we find that, overall, genes that show higher variability in the aggressive subtype are related to cell cycle, development and inter-cellular communication, probably related to faster progression of this disease subtype. Conclusions: There are strong relations between disease subtype and gene expression variability linking significantly increased expression variability to phenotypes such as aggressiveness and resistance to therapy in CLL.


2014 ◽  
Vol 306 (4) ◽  
pp. G346-G356 ◽  
Author(s):  
Lenka Polidarová ◽  
Lucie Olejníková ◽  
Lucia Paušlyová ◽  
Martin Sládek ◽  
Matúš Soták ◽  
...  

Colonic morphology and function change significantly during ontogenesis. In mammals, many colonic physiological functions are temporally controlled by the circadian clock in the colon, which is entrained by the central circadian clock in the suprachiasmatic nuclei (SCN). The aim of this present study was to ascertain when and how the circadian clock in the colon develops during the perinatal period and whether maternal cues and/or the developing pup SCN may influence the ontogenesis of the colonic clock. Daily profiles of clock genes Per1, Per2, Cry1, Cry2, Rev-erbα, Bmal1, and Clock expression in the colon underwent significant modifications since embryonic day 20 (E20) through postnatal days (P) 2, 10, 20, and 30 via changes in the mutual phasing among the individual clock gene expression rhythms, their relative phasing to the light-dark regime, and their amplitudes. An adult-like state was achieved around P20. The foster study revealed that during the prenatal period, the maternal circadian phase may partially modulate development of the colonic clock. Postnatally, the absence and/or presence of rhythmic maternal care affected the phasing of the clock gene expression profiles in pups at P10 and P20. A reversal in the colonic clock phase between P10 and P20 occurred in the absence of rhythmic signals from the pup SCN. The data demonstrate ontogenetic maturation of the colonic clock and stress the importance of prenatal and postnatal maternal rhythmic signals for its development. These data may contribute to the understanding of colonic function-related diseases in newborn children.


2010 ◽  
Vol 28 (15_suppl) ◽  
pp. e12503-e12503
Author(s):  
D. Dréau ◽  
J. M. Eddy ◽  
K. Thompson ◽  
J. Weller ◽  
J. Dollar ◽  
...  

Author(s):  
Benjamin A. Taylor ◽  
Alessandro Cini ◽  
Christopher D. R. Wyatt ◽  
Max Reuter ◽  
Seirian Sumner

AbstractPhenotypic plasticity, the ability to produce multiple phenotypes from a single genotype, represents an excellent model with which to examine the relationship between gene expression and phenotypes. Despite this, analyses of the molecular bases of plasticity have been limited by the challenges of linking individual phenotypes with individual-level gene expression profiles, especially in the case of complex social phenotypes. Here, we tackle this challenge by analysing the individual-level gene expression profiles of Polistes dominula paper wasps following the loss of a queen, a perturbation that induces some individuals to undergo a significant phenotypic shift and become replacement reproductives. Using a machine learning approach, we find a strong response of caste-associated gene expression to queen loss, wherein individuals’ expression profiles become intermediate between queen and worker states. Importantly, this change occurs even in individuals that appear phenotypically unaffected. Part of this response is explained by individual attributes, most prominently age. These results demonstrate that large changes in gene expression may occur in the absence of detectable phenotypic changes, resulting here in a socially mediated de-differentiation of individuals at the transcriptomic but not the phenotypic level. Our findings also highlight the complexity of the relationship between gene expression and phenotype, where transcriptomes are neither a direct reflection of the genotype nor a proxy for the molecular underpinnings of the external phenotype.


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