Suppression of Progenitor Differentiation Requires the Long Non-Coding RNA ANCR
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Kun Qu
PROVIDER: E-GEOD-34767 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Long non-coding RNAs (lncRNAs) regulate diverse processes, yet a potential role for lncRNAs in maintaining the undifferentiated state in somatic tissue progenitor cells remains uncharacterized. We used transcriptome sequencing and tiling arrays to compare lncRNA expression in epidermal progenitor populations versus differentiating cells. We identified ANCR (anti differentiation ncRNA) as an 855 bp lncRNA down-regulated during differentiation. Depleting ANCR in progenitor-containing populations, without any other stimuli, led to rapid differentiation gene induction. In epidermis, ANCR loss abolished the normal exclusion of differentiation from the progenitor-containing compartment. The ANCR lncRNA is thus required to enforce the undifferentiated cell state within epidermis. Custom tiling arrays designed to assay the intergenic space corresponding to regions of H3K4me3-H3K36me3 domains (Khalil et al., 2009) were used to assay changes in RNA expression of putative lncRNAs. RNA from progenitor populations and terminally differentiated populations of human keratinocytes, adipocytes, and osteoblasts were hybridized to these arrays and differential expression was assessed.
2012-01-01 | E-GEOD-34766 | biostudies-arrayexpress
Project description:Long non-coding RNAs (lncRNAs) regulate diverse processes, yet a potential role for lncRNAs in maintaining the undifferentiated state in somatic tissue progenitor cells remains uncharacterized. We used transcriptome sequencing and tiling arrays to compare lncRNA expression in epidermal progenitor populations versus differentiating cells. We identified ANCR (anti differentiation ncRNA) as an 855 bp lncRNA down-regulated during differentiation. Depleting ANCR in progenitor-containing populations, without any other stimuli, led to rapid differentiation gene induction. In epidermis, ANCR loss abolished the normal exclusion of differentiation from the progenitor-containing compartment. The ANCR lncRNA is thus required to enforce the undifferentiated cell state within epidermis. Gene expression analysis: To establish the global gene regulatory effects of ANCR depletion, total RNA was isolated in biologic duplicate from cells in different conditions and hybridized to Affymetrix HG-U133 2.0 Plus arrays.
2012-01-01 | E-GEOD-34528 | biostudies-arrayexpress
Project description:The aim of this study was to establish a deeply sequenced transcriptome at multiple timepoints during the differentiation of human epidermal keratinocytes from the progenitor state (d0). These transcriptomes were then assembled in order to discover novel genes and transcriptional events that are dynamically regulated during terminal differentiation of a human somatic tissue. Paired-end RNA sequencing was performed on primary human keratinocytes at three timepoints during calcium-induced epidermal differentiation.
2012-02-02 | E-GEOD-35468 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-06-02 | E-GEOD-58161 | biostudies-arrayexpress
Project description:Progenitor cells maintain self-renewing tissues throughout life by sustaining their capacity for proliferation while suppressing cell cycle exit and terminal differentiation. DNA methylation provides a potential epigenetic mechanism for the cellular memory needed to preserve the somatic progenitor state through repeated cell divisions. DNA methyltransferase 1 (DNMT1) maintains DNA methylation patterns after cellular replication. Although dispensable for embryonic stem cell maintenance, a clear role for DNMT1 in maintaining the progenitor state in constantly replenished somatic tissues, such as mammalian epidermis, is uncharacterized. Here we show that DNMT1 is essential for supporting epidermal progenitor cell function. DNMT1 protein was found enriched in undifferentiated cells, where it was required to retain proliferative stamina and suppress differentiation. In tissue, DNMT1 depletion led to exit from the progenitor cell compartment, premature differentiation and eventual tissue loss. These effects correlated with DNA methylation as genome-wide analysis revealed that a significant portion of epidermal differentiation gene promoters were methylated in self-renewing conditions but were subsequently demethylated during differentiation. Gene expression analysis: To establish a differentiation signature for primary human keratinocytes, total RNA was isolated in biologic duplicate from cells cultured in growth conditions and high calcium differentiation conditions and hybridized to Affymetrix HG-U133 2.0 Plus arrays. This gene signature was also compared to DNMT1 deficient cells cultured in growth conditions. Methylated DNA profiling: To globally characterize DNA methylation in primary human keratinocytes, genomic DNA was immunoprecipitated using a 5-methylcytidine antibody, amplified, and hybridized to NimbleGen HG18 promoter tiling arrays. Profiling was done using DNA isolated in growth conditions as well as differentiation conditions.
2010-06-23 | E-GEOD-18590 | biostudies-arrayexpress
Project description:Somatic progenitors suppress differentiation to maintain tissue self-renewal. While epigenetic regulators of DNA and histone modifications can support such repression, a role for nuclear actin-like proteins is unclear. In epidermis, ACTL6a/BAF53A was found enriched in progenitors and down-regulated during differentiation. Conditional ACTL6a deletion abolished epidermal self-renewal and induced terminal differentiation, whereas ectopically expressed ACTL6a suppressed differentiation. Among known activators of epidermal differentiation, KLF4 was found to control 227 genes also regulated by ACTL6a. ACTL6a loss upregulated KLF4 and its target genes, effects that were blocked by KLF4 depletion. Among multiple ACTL6a-interacting epigenetic regulators, the SWI/SNF complex was required for KLF4 activation and differentiation. In progenitors, ACTL6a loss led to enhanced SWI/SNF binding to the promoters of KLF4 and other differentiation genes. ACTL6a thus maintains the undifferentiated progenitor state, in part by suppressing SWI/SNF complex-enabled induction of KLF4. Gene expression analysis: To identify the gene set controlled by ACTL6a in human keratinocyte. Total RNA was isolated in biologic duplicate from cells with ACTL6a loss as compared to controls, and hybridized to Affymetrix HG-U133 2.0 Plus arrays.
2012-11-30 | E-GEOD-36222 | biostudies-arrayexpress
Project description:Disrupted differentiation is a hallmark of numerous diseases, which in epidermis alone impact >25% of the population. In a search for dominant mediators of differentiation, we defined a requirement for the ZNF750 nuclear protein in terminal epidermal differentiation. ZNF750 controlled genes mutated in numerous human skin diseases, including FLG, LOR, LCE3B, ALOXE3, and SPINK5. ZNF750 potently induced progenitor differentiation via an evolutionarily conserved C2H2 zinc finger motif. The epidermal master regulator, p63, bound the ZNF750 promoter and was necessary for its induction. ZNF750 restored differentiation to p63-deficient tissue, suggesting it acts downstream of p63. A search for functionally important ZNF750 targets via analysis of ZNF750-regulated genes identified KLF4, a transcription factor that activates late epidermal differentiation genes. ZNF750 binds the Klf4 promoter and controls its expression. ZNF750 thus provides a direct link between a tissue-specifying factor, p63, and an effector of terminal differentiation, Klf4, and represents a potential future target for disorders of this process. Gene expression analysis: To establish a differentiation signature for primary human keratinocytes, with ZNF750-depleted, and Klf4-depleted, total RNA was isolated in biologic duplicate from cells in different conditions and hybridized to Affymetrix HG-U133 2.0 Plus arrays.
2012-02-15 | E-GEOD-32685 | biostudies-arrayexpress
Project description:EGFR activation is important in human epithelial malignancies, including cutaneous squamous cell carcinoma, lung, colon, pancreatic and other cancers. Therapies targeting EGFR are currently used to treat such cancers, but one significant drawback to EGFR inhibitor therapies is the associated skin toxicity. This toxicity usually presents as papular or pustular folliculitis, dry skin with pruritus and hair and nails abnormalities. The side effects often limit the usefulness of EGFR inhibitors in cancer treatment. The transcriptional changes caused by EGFR inhibition in epidermal keratinocytes have not been extensively explored. To define the transcriptional changes caused by inhibition of EGFR in primary human epidermal keratinocytes, we treated these cells with Tyrphostin and compared treated and control cultures in parallel, using Affymetrix microarrays. Using metaanalysis approaches, we integrated the observed changes with a large set of already existing data on transcriptional profiling in epidermal keratinocytes. We found that EGFR inhibition suppresses expression of genes associated with keratinocyte proliferation, attachment and motility. Apoptosis is facilitated by both induction of proapoptotic and suppression of antiapoptotic genes. Surprisingly, EGFR inhibition induces expression of markers of epidermal differentiation. Time course of human epidermal keratinocytes treated with Tyrphostin (AG1478) and untreated controls
2012-10-19 | E-GEOD-41680 | biostudies-arrayexpress
Project description:Suppression of progenitor differentiation requires the long noncoding RNA ANCR
| PRJNA251407 | ENA
Project description:The near-normalization of constitutive cytokine and matrix release following rescue by HPS1 transduction of HPM cells suggests that HPS-1 HuMCs may contribute to pulmonary fibrosis and constitute a target for therapeutic intervention. Microarray analysis of HPS-1 HuMCs and non-transduced HPM cells confirmed upregulation of differentially expressed genes involved in fibrogenesis and degranulation. Six HPS-1 patients and five healthy controls were studied following informed consent. One typical HPS-1 HuMC culture at 5-6 weeks was eventually overgrown by a population of smaller, rapidly dividing cells. Analysis of differential gene expression from 8 wk old control and HPS-1 HuMCs and HPM cells was performed using cDNA generated from cultured cells.
2016-07-01 | E-GEOD-83920 | biostudies-arrayexpress