Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A genome-wide long noncoding RNA CRISPRi screen identifies PRANCR as a novel regulator of epidermal homeostasis

ABSTRACT: Long noncoding RNAs (lncRNAs) are a major component of the noncoding genome, but their functions in human development and disease are still incompletely understood. CRISPR interference screens allow for systematic identification of functional lncRNAs that regulate fundamental biological processes such as tissue development and homeostasis. We identified 2,263 lncRNAs transcribed in human epidermis, and performed a comprehensive CRISPR interference screen against all these elements in primary human epidermal progenitors. Our screen identified 209 lncRNAs controlling epidermal progenitor renewal, with the majority (94%) being positive regulators of proliferation. To validate the results, we performed deeper characterization of a novel lncRNA identified from this screen, PRANCR (LINC01481), using RNA interference-mediated transcript knockdown and phenotype analysis in organotypic human tissue. PRANCR depletion inhibited progenitor proliferation through a G2/M cell cycle arrest, reduced clonogenic potential, and impaired functional epidermal stratification. Transcriptome and computational analysis indicated that PRANCR governs progenitor renewal by controlling the expression of 1,136 genes in trans, in part via the p53-E2F4-CHR pathway. This pathway controls the expression of G2/M cell cycle genes and is a novel mechanism of regulating cell proliferation in epidermal progenitors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE125400 | GEO | 2019/11/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Trincr1 RNA pull down MS in mESC

Project description:Long noncoding RNAs (lncRNAs) have emerged as important components of gene regulatory network in embryonic stem cells (ESCs). However, the function and molecular mechanism of lncRNAs are still largely unknown. Here we identified Trincr1 (TRIM71 interacting long noncoding RNA 1) lncRNA that regulates the FGF/ERK signaling and self-renewal of ESCs. Trincr1 is exported by THOC complex to cytoplasm where it binds and represses TRIM71, leading to the downregulation of SHCBP1 protein. Knocking out Trincr1 leads to the upregulation of phosphorylated ERK and ERK pathway target genes and the decrease of ESC self-renewal, while knocking down Trim71 completely rescues the defects of Trincr1 knockout. Furthermore, ectopic expression of Trincr1 represses FGF/ERK signaling and the self-renewal of neural progenitor cells. Together, this study reveals more regulators in FGF/ERK signaling pathway and highlights lncRNA as an important player in cell signaling network to coordinate cell fate specification.

2019-02-01 | PXD012493 | Pride

Gene expression data of human primary keratinocytes with control or DDX6 knockdown

Project description:Stem and progenitor cells maintain the tissue they reside in for life by regulating the balance between proliferation and differentiation. How this is done is not well understood. Here, we report that DDX6 is necessary for maintaining human epidermal progenitor cell self-renewal. Global gene expression profiling using U133 plus 2.0 arrays were used to deteremine the genes perturbed by knockdown of DDX6.

2015-10-01 | GSE62417 | GEO

Computational prediction and experimental validation identify functionally conserved lncRNAs from zebrafish to human

Project description:Functional studies of long noncoding RNAs (lncRNAs) have long been hindered by a lack of methods to assess their evolution. Here, we present lncHOME (lncRNA Homology Explorer), a computational pipeline that identifies a unique coPARSE-lncRNA class with conserved genomic locations and patterns of RNA binding protein (RBP) binding sites. Remarkably, several hundred human coPARSE-lncRNAs can be evolutionarily traced to zebrafish. Using CRISPR-Cas12a knockout and rescue assays, we found that knocking out many human coPARSE-lncRNAs led to cell proliferation defects that were rescued by predicted zebrafish homologs. Knocking down the coPARSE-lncRNAs in zebrafish embryos caused severe developmental delays that were rescued by human homologs. Moreover, we verified that human, mouse, and zebrafish coPARSE-lncRNA homologs tend to bind similar RBPs with their conserved fuctions relying on specific RBP binding sites. Overall, our study demonstrates a comprehensive approach for studying functional conservation of lncRNAs and implicates numerous lncRNAs in regulating cellular physiology.

2024-01-26 | PXD046452 | Pride

The long non-coding RNA LINC00941 modulates MTA2/NuRD occupancy to suppress premature human epidermal differentiation

Project description:Numerous long non-coding RNAs (lncRNAs) were shown to have functional impact on cellular processes, such as human epidermal homeostasis, but for only a few the mode of action has been elucidated. Here, we report that lncRNA LINC00941 controls keratinocyte differentiation on a global level through association with the MTA2/NuRD complex, one of the major chromatin remodelers in cells. LINC00941 was found to interact with NuRD-associated MTA2, suppressing the expression of the transcription factor EGR3, a regulator of epidermal differentiation. Both LINC00941 and the MTA2/NuRD complex are enriched in non-differentiated keratinocytes and repress the expression of differentiation genes through epigenetic silencing of EGR3, consequentially preventing premature differentiation of human progenitor cells.

2024-04-08 | PXD043838 | Pride

Identification of ETV4-responsive genes in NSCLC cells

Project description:H1703, H1299, and H358T cells treated with or without si-ETV4 were used to screen the global profiling of human long-noncoding RNAs (lncRNAs) and protein-coding transcripts.

2022-12-31 | GSE137475 | GEO

A TRIM71 binding long noncoding RNA Trincr1 represses FGF/ERK signaling in embryonic stem cells

Project description:Long noncoding RNAs (lncRNAs) have emerged as important components of gene regulatory network in embryonic stem cells (ESCs). However, the function and molecular mechanism of lncRNAs are still largely unknown. Here we identified Trincr1 (TRIM71 interacting long noncoding RNA 1) lncRNA that regulates the FGF/ERK signaling and self-renewal of ESCs. Trincr1 is exported by THOC complex to cytoplasm where it binds and represses TRIM71, leading to the downregulation of SHCBP1 protein. Knocking out Trincr1 led to the upregulation of phosphorylated ERK and ERK pathway target genes and the decrease of ESC self-renewal, while knocking down Trim71 completely rescued the defects of Trincr1 knockout. Furthermore, ectopic expression of Trincr1 repressed FGF/ERK signaling and the self-renewal of neural progenitor cells. Together, this study reveals novel regulators in FGF/ERK signaling pathway and highlights lncRNA as an important player in cell signaling network to coordinate cell fate specification.

2019-01-23 | GSE125458 | GEO

Gene expression data of human primary keratinocytes with control, EXOSC9 or EXOSC9+GRHL3 knockdown

Project description:Stem and progenitor cells maintain the tissue they reside in for life by regulating the balance between proliferation and differentiation. How this is done is not well understood. Here, we report that the human exosome maintains progenitor cell function. The expression of several subunits of the exosome were found to be enriched in epidermal progenitor cells, which were required to retain proliferative capacity and to prevent premature differentiation. Loss of PM/Scl-75 also known as EXOSC9, a key subunit of the exosome complex, resulted in loss of cells from the progenitor cell compartment, premature differentiation, and loss of epidermal tissue. EXOSC9 promotes self-renewal and prevents premature differentiation by maintaining transcript levels of a transcription factor necessary for epidermal differentiation, GRHL3, at low levels through mRNA degradation. These data demonstrate that control of differentiation specific transcription factors through mRNA degradation is required for progenitor cell maintenance in mammalian tissue. Refer to publication (Mistry et. Cell Stem Cell 2012) for more detail For gene expression profiling, cultured primary human keratinocytes were knocked down for EXOSC9, EXOSC9 and GRHL3, or control. RNA was harvested from the cells 5 days after knockdown. Microarray analysis using Affymetrix HG-U133 2.0 plus arrays was performed on duplicate samples. Significantly changed genes were identified as previously described(Sen et al., 2010).

2012-04-27 | E-GEOD-37637 | biostudies-arrayexpress

Development of gene expression signatures for NSCLC

Project description:Eight frozen tissues of NSCLCs (4 SCCs and 4 ACs) and paired normal lung tissues were used to screen the global profiling of human long-noncoding RNAs (lncRNAs) and protein-coding transcripts.

2019-09-14 | GSE137445 | GEO

Gene expression data of human primary keratinocytes with control, EXOSC9 or EXOSC9+GRHL3 knockdown

Project description:Stem and progenitor cells maintain the tissue they reside in for life by regulating the balance between proliferation and differentiation. How this is done is not well understood. Here, we report that the human exosome maintains progenitor cell function. The expression of several subunits of the exosome were found to be enriched in epidermal progenitor cells, which were required to retain proliferative capacity and to prevent premature differentiation. Loss of PM/Scl-75 also known as EXOSC9, a key subunit of the exosome complex, resulted in loss of cells from the progenitor cell compartment, premature differentiation, and loss of epidermal tissue. EXOSC9 promotes self-renewal and prevents premature differentiation by maintaining transcript levels of a transcription factor necessary for epidermal differentiation, GRHL3, at low levels through mRNA degradation. These data demonstrate that control of differentiation specific transcription factors through mRNA degradation is required for progenitor cell maintenance in mammalian tissue. Refer to publication (Mistry et. Cell Stem Cell 2012) for more detail

2012-04-28 | GSE37637 | GEO

Suppression of Progenitor Differentiation Requires the Long Non-Coding RNA ANCR [lincRNA 391k Tiling Array V2]

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data