Please use this identifier to cite or link to this item: doi:10.22028/D291-42633
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Title: Activation of HERV-K(HML-2) disrupts cortical patterning and neuronal differentiation by increasing NTRK3
Author(s): Padmanabhan Nair, Vidya
Liu, Hengyuan
Ciceri, Gabriele
Jungverdorben, Johannes
Frishman, Goar
Tchieu, Jason
Cederquist, Gustav Y.
Rothenaigner, Ina
Schorpp, Kenji
Klepper, Lena
Walsh, Ryan M.
Kim, Tae Wan
Cornacchia, Daniela
Ruepp, Andreas
Mayer, Jens
Hadian, Kamyar
Frishman, Dmitrij
Studer, Lorenz
Vincendeau, Michelle
Language: English
Title: Cell Stem Cell
Volume: 28
Issue: 9
Pages: 1566-1581
Publisher/Platform: Cell Press
Year of Publication: 2021
Free key words: HERV
endogenous retrovirus
retrotransposon
CRISPR
influencing cortical neuronal development
Neurotrophic Tyrosine Receptor Kinase 3
NTRK3
forebrain orgnoid
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: The biological function and disease association of human endogenous retroviruses (HERVs) are largely elusive. HERV-K(HML-2) has been associated with neurotoxicity, but there is no clear understanding of its role or mechanistic basis. We addressed the physiological functions of HERV-K(HML-2) in neuronal differentiation using CRISPR engineering to activate or repress its expression levels in a human-pluripotent-stemcell-based system. We found that elevated HERV-K(HML-2) transcription is detrimental for the development and function of cortical neurons. These effects are cell-type-specific, as dopaminergic neurons are unaffected. Moreover, high HERV-K(HML-2) transcription alters cortical layer formation in forebrain organoids. HERV-K(HML-2) transcriptional activation leads to hyperactivation of NTRK3 expression and other neurodegeneration-related genes. Direct activation of NTRK3 phenotypically resembles HERV-K(HML-2) induction, and reducing NTRK3 levels in context of HERV-K(HML-2) induction restores cortical neuron differentiation. Hence, these findings unravel a cell-type-specific role for HERV-K(HML-2) in cortical neuron development.
DOI of the first publication: 10.1016/j.stem.2021.04.009
URL of the first publication: https://doi.org/10.1016/j.stem.2021.04.009
Link to this record: urn:nbn:de:bsz:291--ds-426331
hdl:20.500.11880/38236
http://dx.doi.org/10.22028/D291-42633
ISSN: 1934-5909
Date of registration: 12-Aug-2024
Description of the related object: Supplemental information
Related object: https://ars.els-cdn.com/content/image/1-s2.0-S1934590921001661-mmc1.pdf
https://ars.els-cdn.com/content/image/1-s2.0-S1934590921001661-mmc2.pdf
Faculty: M - Medizinische Fakultät
Department: M - Humangenetik
Professorship: M - Prof. Dr. Eckart Meese
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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