Bovine articular chondrocytes were grown in micromass culture and were either untreated or treated with 5 ng TGF-b1/ml for 8 hours to identify genes regulated by TGF-b.
Altered responsiveness to TGF-β results in reduced Papss2 expression and alterations in the biomechanical properties of mouse articular cartilage.
Specimen part, Treatment
View SamplesWe used microarrays to study the effect of Chd1 loss of function in mouse ES cells.
Chd1 regulates open chromatin and pluripotency of embryonic stem cells.
Cell line
View SamplesPurpose: Validation of Drosophila A-to-I editing sites Methods: We collected heads of 5 day old male dAdar-/- mutant (y, Adar5G1, w)26 and wild type (w1118) flies. Poly(A)+ RNA was used to prepare RNA-seq libraries which were subsequently sequenced single-end by an Illumina GAII Results:We builded a framework to identify RNA editing events using RNA-seq data alone in Drosophila. To validate whether the identified A-to-G sites were bona fide A-to-I editing events, we performed RNA-seq for the D.melanogaster wild-type strain (w1118) and for the Adar5G1 null mutant that eliminates RNA editing. We found that our method achieved high accuracy; 98.2% of all A-to-G sites showed only adenosine in the Adar5G1 sample Conclusions: We anticipate that our method will be very effective in the future to identify RNA editing events in different species. Overall design: mRNA profiles of heads of 5 day old male dAdar-/- mutant (y, Adar5G1, w)26 and wild type (w1118) flies
Identifying RNA editing sites using RNA sequencing data alone.
Age, Specimen part, Cell line, Subject
View SamplesPluripotent stem cells are being actively studied as a cell source for regenerating damaged liver. For long term survival of engrafting cells in the body, not only do the cells have to execute liverspecific function but also withstand the physical strains and invading pathogens. The cellular innate immune system orchestrated by the interferon (IFN) pathway provides the first line of defense against pathogens. The objective of this study is to assess the innate immune function as well as to systematically profile the IFN-induced genes during hepatic differentiation of pluripotent stem cells. To address this objective, we derived endodermal cells (day 5 postdifferentiation), hepatoblast (day 15) and immature hepatocytes (day 21) from human embryonic stem cells (hESC). Day 5, 15 and 21 cells were stimulated with IFN-a and subjected to IFN pathway analysis. Transcriptome analysis was carried out by RNA sequencing. The results showed that the IFN-a treatment activated STAT-JAK pathway in differentiating cells. Transcriptome analysis indicated stage specific expression of classical and non-classical IFNstimulated genes (ISGs). Subsequent validation confirmed the expression of novel ISGs including RASGRP3, CLMP and TRANK1 by differentiated hepatocytes upon IFN treatment. Hepatitis C virus replication in hESC-derived hepatic cells induced the expression of ISGs – LAMP3, ETV7, RASGRP3, and TRANK1. The hESC-derived hepatic cells contain intact innate system and can recognize invading pathogens. Besides assessing the tissue-specific functions for cell therapy applications, it may also be important to test the innate immune function of engrafting cells to ensure adequate defense against infections and improve graft survival. Overall design: 12 samples total, 4 samples in each time point (day 5, day 15, day 21). Each group of 4 within each time point has 2 control and 2 treatment samples in which the cells were stimulated with human interferon-alpha A (R and D Systems) at a concentration of 5000 IU for 6 hours.
Characterization of type I interferon pathway during hepatic differentiation of human pluripotent stem cells and hepatitis C virus infection.
No sample metadata fields
View SamplesMicroarray analysis on total retinal RNA from 15 day old Sirt6 wild-type (WT) and knock-out (KO) mice.
SIRT6 is required for normal retinal function.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
ACTL6A Is Co-Amplified with p63 in Squamous Cell Carcinoma to Drive YAP Activation, Regenerative Proliferation, and Poor Prognosis.
Cell line, Treatment
View SamplesThe reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) upon overexpression of OCT4, KLF4, SOX2 and c-MYC (OKSM) provides a powerful system to interrogate basic mechanisms of cell fate change. However, iPSC formation with standard methods is typically protracted and inefficient, resulting in heterogeneous cell populations. We show that exposure of OKSM-expressing cells to both ascorbic acid and a GSK3- inhibitor (AGi) facilitates more synchronous and rapid iPSC formation from several mouse cell types. AGi treatment restored the ability of refractory cell populations to yield iPSC colonies, and it attenuated the activation of developmental regulators commonly observed during the reprogramming process. Moreover, AGi supplementation gave rise to chimera-competent iPSCs after as little as 48 h of OKSM expression. Our results offer a simple modification to the reprogramming protocol, facilitating iPSC induction at unparalleled efficiencies and enabling dissection of the underlying mechanisms in more homogeneous cell populations.
Small molecules facilitate rapid and synchronous iPSC generation.
Specimen part, Treatment, Time
View SamplesLoss-of-function mutations in SWI/SNF chromatin remodeling subunit genes are observed in many cancers, but an oncogenic role for SWI/SNF is not well established. Here we reveal that ACTL6A, encoding a SWI/SNF subunit linked to stem and progenitor cell function, is frequently co-amplified and highly expressed together with the p53 family member p63 in head and neck squamous cell carcinoma (HNSCC). ACTL6A and p63 physically interact and cooperatively control a transcriptional program that promotes proliferation and suppresses differentiation, in part through activation of the Hippo-YAP pathway via regulators including WWC1. Consequently, loss of ACTL6A or p63 in tumor cells induces YAP phosphorylation and inactivation, associated with growth arrest and terminal differentiation, all phenocopied by WWC1 overexpression. In vivo, ectopic ACTLC6A/p63 expression promotes tumorigenesis, while ACTL6A expression and YAP activation are highly correlated in primary HNSCC and predict poor patient survival. Thus, ACTL6A and p63 collaborate as oncogenic drivers in HNSCC.
ACTL6A Is Co-Amplified with p63 in Squamous Cell Carcinoma to Drive YAP Activation, Regenerative Proliferation, and Poor Prognosis.
Cell line, Treatment
View SamplesLoss-of-function mutations in SWI/SNF chromatin remodeling subunit genes are observed in many cancers, but an oncogenic role for SWI/SNF is not well established. Here we reveal that ACTL6A, encoding a SWI/SNF subunit linked to stem and progenitor cell function, is frequently co-amplified and highly expressed together with the p53 family member p63 in head and neck squamous cell carcinoma (HNSCC). ACTL6A and p63 physically interact and cooperatively control a transcriptional program that promotes proliferation and suppresses differentiation, in part through activation of the Hippo-YAP pathway via regulators including WWC1. Consequently, loss of ACTL6A or p63 in tumor cells induces YAP phosphorylation and inactivation, associated with growth arrest and terminal differentiation, all phenocopied by WWC1 overexpression. In vivo, ectopic ACTLC6A/p63 expression promotes tumorigenesis, while ACTL6A expression and YAP activation are highly correlated in primary HNSCC and predict poor patient survival. Thus, ACTL6A and p63 collaborate as oncogenic drivers in HNSCC.
ACTL6A Is Co-Amplified with p63 in Squamous Cell Carcinoma to Drive YAP Activation, Regenerative Proliferation, and Poor Prognosis.
Cell line, Treatment
View SamplesLoss-of-function mutations in SWI/SNF chromatin remodeling subunit genes are observed in many cancers, but an oncogenic role for SWI/SNF is not well established. Here we reveal that ACTL6A, encoding a SWI/SNF subunit linked to stem and progenitor cell function, is frequently co-amplified and highly expressed together with the p53 family member p63 in head and neck squamous cell carcinoma (HNSCC). ACTL6A and p63 physically interact and cooperatively control a transcriptional program that promotes proliferation and suppresses differentiation, in part through activation of the Hippo-YAP pathway via regulators including WWC1. Consequently, loss of ACTL6A or p63 in tumor cells induces YAP phosphorylation and inactivation, associated with growth arrest and terminal differentiation, all phenocopied by WWC1 overexpression. In vivo, ectopic ACTLC6A/p63 expression promotes tumorigenesis, while ACTL6A expression and YAP activation are highly correlated in primary HNSCC and predict poor patient survival. Thus, ACTL6A and p63 collaborate as oncogenic drivers in HNSCC.
ACTL6A Is Co-Amplified with p63 in Squamous Cell Carcinoma to Drive YAP Activation, Regenerative Proliferation, and Poor Prognosis.
Cell line, Treatment
View Samples