We report on explant osteoblast cultures from human patients, demonstrating that there are at least three sub-types of non-syndromic craniosynostosis defined by similarity of gene expression profiles. Overall design: Osteoblast growth in culture, 23 craniosynostosis skull samples (7 metopic; 8 coronal; 3 lambdoid; 5 sagittal) and 8 normal (4 cranial bones and 4 long bones)
Characterization of distinct classes of differential gene expression in osteoblast cultures from non-syndromic craniosynostosis bone.
No sample metadata fields
View SamplesRATIONALE: Idiopathic pulmonary fibrosis (IPF) is a fatal disease with overtly scarred peripheral and basilar lung regions and macroscopically unaffected central lung areas. OBJECTIVES: To gain better insight into IPF pathobiology by comparing transcriptomic profiles of normal-appearing and scarred regions of IPF lung. METHODS: Lung tissue samples from macroscopically unaffected (normal-appearing, IPFn) and scarred (IPFs) regions of explanted IPF lungs were analyzed by RNASeq and compared with healthy control (HC) lung tissues. RT-qPCR and immunohistochemistry were used to confirm selected findings. MEASUREMENTS AND RESULTS: Numerous previously reported IPF-associated gene expression disturbances as well as additional differentially expressed mRNAs were observed. There were profound transcriptomic changes in IPFn compared with HC tissues, which included elevated expression of extracellular matrix-, immunity- and inflammation-related mRNAs. The magnitude and statistical significance of these changes were comparable or greater than those in the IPFs-to-HC comparison. When directly compared with IPFn, IPFs tissues demonstrated elevated expression of epithelial mucociliary mRNAs. Compared with HC, both IPFn and IPFs tissues demonstrated reduced expression of mRNAs related to solute carrier membrane transport and metabolic processes. Primary fibroblast cultures from IPFn and IPFs tissues were transcriptomically identical. CONCLUSIONS: Macroscopically normal-appearing IPF tissues demonstrate profound disease activity and substantially similar transcriptomic profiles to scarred areas. Differences between these tissues are due to cell types other than fibroblasts and notably include enhanced expression of mucociliary genes in scarred areas. Deranged epithelial homeostasis or possibly non-transcriptomic factors may thus explain the marked architectural differences between normal-appearing and terminally scarred lung in end-stage IPF. Overall design: RNASeq of 26 lung tissue samples from patients with IPF, including affected and unaffected areas of the lung, and from healthy controls
Transcriptomic evidence of immune activation in macroscopically normal-appearing and scarred lung tissues in idiopathic pulmonary fibrosis.
Specimen part, Disease, Subject
View SamplesThe SCL and LMO1 oncogenic transcription factors reprogram thymocytes into self-renewing pre-leukemic stem cells (pre-LSCs). Here we report that SCL directly interacts with LMO1 to activate the transcription of a self-renewal program coordinated by LYL1.
SCL, LMO1 and Notch1 reprogram thymocytes into self-renewing cells.
Age, Specimen part
View SamplesWe have recently demonstrated that mycobacterial ligands engage Toll like receptor 2 (TLR2) on CD4+ T cells and up-regulate T-cell receptor (TCR) triggered- Th1 responses in vitro and in vivo.
Toll like Receptor 2 engagement on CD4<sup>+</sup> T cells promotes TH9 differentiation and function.
No sample metadata fields
View SamplesMHC-I overexpression in muscle biopsies is a hallmark of inflammatory myopathies.However the mechanisms of MHC-I overexpression in each disease is not well understood. Microarray analysis from MHC-I-microdissected myofibers showed a differential expression signature in each inflammatory myopathy. Innate immunity and IFN-I pathways are upregulated vs healthy controls, specifically in dermatomyositis (DM).
Altered RIG-I/DDX58-mediated innate immunity in dermatomyositis.
Specimen part, Disease
View SamplesThe second heart field (SHF) comprises a population of mesodermal progenitor cells that are added to the nascent linear heart to give rise to the majority of the right ventricle, interventricular septum, and outflow tract of mammals and birds. The zinc finger transcription factor GATA4 functions as an integral member of the cardiac transcription factor network in the SHF and its derivatives. In addition to its role in cardiac differentiation, GATA4 is also required for cardiomyocyte replication, although the transcriptional targets of GATA4 required for proliferation have not been previously identified. In the present study, we disrupted Gata4 function exclusively in the SHF and its derivatives. Gata4 SHF knockout mice die by embryonic day 13.5 and exhibit hypoplasia of the right ventricular myocardium and interventricular septum and display profound ventricular septal defects. Loss of Gata4 function in the SHF results in decreased myocyte proliferation in the right ventricle, and we identify numerous cell cycle genes that are dependent on Gata4 by microarray analysis. We show that Gata4 is required for Cyclin D2 expression in the right ventricle and that the Cyclin D2 promoter is bound and activated by GATA4 via three consensus GATA binding sites. These findings establish Cyclin D2 as a direct transcriptional target of GATA4 and support a model in which GATA4 controls cardiomyocyte proliferation by coordinately regulating numerous cell cycle genes.
GATA4 is a direct transcriptional activator of cyclin D2 and Cdk4 and is required for cardiomyocyte proliferation in anterior heart field-derived myocardium.
No sample metadata fields
View SamplesThe implantation process begins with attachment of the trophectoderm (TE) of the blastocyst to the maternal endometrial epithelium. Herein we have investigated the transcriptome of mural TE cells from 13 human blastocysts and compared these with those of human embryonic stem cell (hESC)-derived-TE (hESCtroph). The transcriptomes of hESFtroph at days 8, 10, and 12 had the greatest consistency with TE. Among genes coding for secreted proteins of the TE of human blastocysts and of hESCtroph are several molecules known to be involved in the implantation process as well as novel ones, such as CXCL12, HBEGF, inhibin A, DKK3, Wnt 5A, follistatin. The similarities between the two lineages underscore some of the known mechanisms and offer discovery of new mechanisms and players in the process of the very early stages of human implantation. We propose that the hESCtroph is a viable functional model of human trophoblasts to study trophoblast-endometrial interactions. Furthermore, the data derived herein offer the promise of novel diagnostics and therapeutics aimed at practical challenges in human infertility and pregnancy disorders associated with abnormal embryonic implantation.
Comparative transcriptome analysis of human trophectoderm and embryonic stem cell-derived trophoblasts reveal key participants in early implantation.
No sample metadata fields
View SamplesProgenitors in human vasculature expanded in-vitro were differentiated with adipogenic cocktail for 12 days, following which they were stimulated with forskolin for 7 days
Human 'brite/beige' adipocytes develop from capillary networks, and their implantation improves metabolic homeostasis in mice.
Specimen part, Treatment
View SamplesIn this experiment, we sought to determine how PRDM14 and CBFA2T2 regulate the transcriptome of mouse embryonic stem cells Overall design: 3 KO mESC lines with 3 biological replicates for each (wild type (3), PRDM14-KO (3), CBFA2T2 (3))
Co-repressor CBFA2T2 regulates pluripotency and germline development.
No sample metadata fields
View SamplesWe have performed conditional inactivation of mef2c in the anterior heart field (AHF) of mice and observed a phenotypic spectrum of outflow tract anomalies in the conditional mutant hearts. In an effort to identify misregulated genes in the outflow tracts of the mutants, we have performed RNA-Seq on outflow tract samples dissected from E10.5 mutant and wild-type embryos. Overall design: There are four wild-type samples and four mutant samples.
MEF2C regulates outflow tract alignment and transcriptional control of Tdgf1.
No sample metadata fields
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