A PBX1 transcriptional network controls dopaminergic neuron development and is impaired in Parkinson’s disease

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F16%3A00090372" target="_blank" >RIV/00216224:14310/16:00090372 - isvavai.cz</a>

Výsledek na webu

<a href="http://emboj.embopress.org/content/embojnl/early/2016/06/28/embj.201593725.full.pdf" target="_blank" >http://emboj.embopress.org/content/embojnl/early/2016/06/28/embj.201593725.full.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.15252/embj.201593725" target="_blank" >10.15252/embj.201593725</a>

Jazyk výsledku

angličtina

Název v původním jazyce

A PBX1 transcriptional network controls dopaminergic neuron development and is impaired in Parkinson’s disease

Popis výsledku v původním jazyce

Pre-B-cell leukemia homeobox (PBX) transcription factors are known to regulate organogenesis, but their molecular targets and function in midbrain dopaminergic neurons (mDAn) as well as their role in neurodegenerative diseases are unknown. Here, we show that PBX1 controls a novel transcriptional network required for mDAn specification and survival, which is sufficient to generate mDAn from human stem cells. Mechanistically, PBX1 plays a dual role in transcription by directly repressing or activating genes, such as Onecut2 to inhibit lateral fates during embryogenesis, Pitx3 to promote mDAn development, and Nfe2l1 to protect from oxidative stress. Notably, PBX1 and NFE2L1 levels are severely reduced in dopaminergic neurons of the substantia nigra of Parkinson’s disease (PD) patients and decreased NFE2L1 levels increases damage by oxidative stress in human midbrain cells.

Název v anglickém jazyce

A PBX1 transcriptional network controls dopaminergic neuron development and is impaired in Parkinson’s disease

Popis výsledku anglicky

Pre-B-cell leukemia homeobox (PBX) transcription factors are known to regulate organogenesis, but their molecular targets and function in midbrain dopaminergic neurons (mDAn) as well as their role in neurodegenerative diseases are unknown. Here, we show that PBX1 controls a novel transcriptional network required for mDAn specification and survival, which is sufficient to generate mDAn from human stem cells. Mechanistically, PBX1 plays a dual role in transcription by directly repressing or activating genes, such as Onecut2 to inhibit lateral fates during embryogenesis, Pitx3 to promote mDAn development, and Nfe2l1 to protect from oxidative stress. Notably, PBX1 and NFE2L1 levels are severely reduced in dopaminergic neurons of the substantia nigra of Parkinson’s disease (PD) patients and decreased NFE2L1 levels increases damage by oxidative stress in human midbrain cells.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EC - Imunologie

OECD FORD obor

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Projekt

<a href="/cs/project/EE2.3.20.0180" target="_blank" >EE2.3.20.0180: Spolupráce mezi Masarykovou univerzitou a Karolinska Institutet, Stockholm na poli biomedicíny</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

The EMBO Journal

ISSN

0261-4189

e-ISSN

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Svazek periodika

35

Číslo periodika v rámci svazku

18

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

16

Strana od-do

1963-1978

Kód UT WoS článku

000384084900003

EID výsledku v databázi Scopus

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