HERV-K(HML-2) transcription in ALS
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ABSTRACT:
PROVIDER: PRJEB23125 | ENA |
REPOSITORIES: ENA
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Project description:The biological function and disease association of human endogenous retroviral (HERV) elements remains largely elusive. We addressed the physiological role of HERV-K(HML-2) in neuronal differentiation by manipulating HERV-K(HML-2) expression levels. We used CRISPR engineering to activate or repress HERV-K(HML-2) and demonstrate that elevated HERV-K(HML-2) transcription is detrimental for development, functionality and growth of cortical neurons. Effects are cell-type specific, as dopaminergic neurons were unaffected. We further show that layer formation is altered during forebrain organoid formation following activation of HERV-K(HML-2) transcription. HERV-K(HML-2) transcriptional activation concurrently elevated Neurotrophic Tyrosine Receptor Kinase 3 (NTRK3) expression along with other neurodegeneration-related genes. Direct transcriptional activation of NTRK3 resembled the HERV-K(HML-2) activation phenotype. Intriguingly, reduction of NTRK3 levels in HERV-K(HML-2)-activated cortical neurons restored differentiated cortical neurons. Hence, our findings unravel a unique cell type-specific mechanism of HERV-K(HML-2) during cortical neuronal differentiation.
2021-03-30 | GSE171101 | GEO
Project description:Elevated transcript expression of the endogenous retrovirus family HERV-K (HML-2) is seen in the majority of breast cancers, although the identity of the individual loci contributing to this expression as well as their mechanism of activation is unclear. Using high-throughput next-generation sequencing techniques optimized for the capture of HML-2 expression, we produced a complete profile of the HML-2 transcriptome before and after human mammary epithelial cell transformation.
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2007-09-26 | E-GEOD-833 | biostudies-arrayexpress
Project description:The purpose of this experiment was to compare the differences in transcript levels between RNA samples collected from fibroblasts from healthy control patients, amyotrophic lateral sclerosis (ALS) patients carrying an expanded GGGGCC repeat mutation in the chromosome 9 open reading frame 72 gene and ALS patients with a mutation in the SOD1 gene.
2013-10-29 | E-MTAB-1926 | biostudies-arrayexpress
Project description:Amyotrophic lateral sclerosis and primary lateral sclerosis are two syndromic variants within the motor neurone disease spectrum. Whilst primary lateral sclerosis is associated with loss of upper motor neurons and a more benign disease course up to 17yrs, amyotrophic lateral sclerosis is caused by loss of both upper and lower motor neurons and has an average disease course of 2-3 years. The majority of cases are sporadic, thereby limiting the availability of cellular models for investigating pathogenic disease mechanisms. The aim of the present study was to evaluate fibroblasts as a cellular model for sporadic amyotrophic lateral sclerosis and primary lateral sclerosis, to establish whether disease-related dysregulated biological processes recapitulate those seen in the central nervous system and to elucidate pathways that distinguish between the two disease phenotypes. We used microarray analysis to determine the differences in gene expression between fibroblasts derived from skin biopsies taken from sporadic amyotrophic lateral sclerosis and primary lateral sclerosis neurologically normal human controls
2014-04-16 | E-GEOD-56808 | biostudies-arrayexpress
Project description:Background: The human genome consists of considerable portions derived from retroviruses inherited for millions of years. So-called human endogenous retroviruses (HERVs) are usually severely mutated, yet some coding-competent HERVs exist. The HERV-K(HML-2) group includes evolutionarily young proviruses that still encode typical retroviral proteins. HERV-K(HML-2) has been implicated in various human diseases because transcription is often upregulated and some of the encoded proteins are known to affect cell biology. HERV-K(HML-2) Protease (Pro) has received little attention so far, although it appears expressed in some disease contexts and other retroviral proteases are known to process cellular proteins. Results: We set out to identify human cellular proteins being substrates of HERV-K(HML-2) Pro employing a modified Terminal Amine Isotopic Labeling of Substrates (TAILS) procedure. Thousands of human proteins were identified as significantly processed by HERV-K(HML-2) Pro. Identified proteins locate to various cellular compartments and participate in diverse, often disease-relevant cellular processes. We verified cleavage of a majority of selected human proteins in vitro and in vivo. Conclusions: Hundreds, if not thousands of cellular proteins are potential substrates of HERV-K(HML-2) Pro. It is conceivable that even low-level expression of HERV-K(HML-2) Pro has a functional impact on cell biology and thus relevance for human diseases. Specific studies will be required to elucidate effects of HERV-K(HML-2) Pro expression regarding human substrate proteins, cell biology and disease. Endogenous retrovirus-encoded Pro activity may also be relevant for disease development in species other than human.
2019-09-02 | PXD013296 | Pride