Adipogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells in Pig Transgenic Model Expressing Human Mutant Huntingtin

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F19%3A00504805" target="_blank" >RIV/67985904:_____/19:00504805 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985891:_____/19:00504805 RIV/68407700:21220/19:00334698 RIV/00216208:11110/19:10404114 RIV/00216208:11140/19:10404114 RIV/00216208:11310/19:10404114

Výsledek na webu

<a href="https://asep.lib.cas.cz/arl-cav/cs/csg/?repo=crepo1&key=68175504893" target="_blank" >https://asep.lib.cas.cz/arl-cav/cs/csg/?repo=crepo1&key=68175504893</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3233/JHD-180303" target="_blank" >10.3233/JHD-180303</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Adipogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells in Pig Transgenic Model Expressing Human Mutant Huntingtin

Popis výsledku v původním jazyce

Background: Although the highest expression of mutant huntingtin (mtHtt) was observed in the brain, its negative effects were also apparent in other tissues. Specifically, mtHtt impairs metabolic homeostasis and causes transcriptional dysregulation in adipose tissue. Adipogenic differentiation can be induced by the activation of two transcription factors: CCAAT/enhancer-binding protein alpha (CEBP alpha) and peroxisome proliferator-activated receptor gamma (PPAR gamma). These same transcription factors were found to be compromised in some tissues of Huntington's disease (HD) mouse models and in lymphocytes of HD patients. nObjective: This study investigated the adipogenic potential of mesenchymal stem cells (MSCs) derived from transgenic Huntington's disease (TgHD) minipigs expressing human mtHtt (1-548aa) containing 124 glutamines. Two differentiation conditions were used, employing PPAR gamma agonist rosiglitazone or indomethacin.nMethods: Bone marrow MSCs were isolated from TgHD and WT minipig siblings and compared by their cluster of differentiation using flow cytometry. Their adipogenic potential in vitro was analyzed using quantitative immunofluorescence and western blot analysis of transcription factors and adipogenic markers. nResults: Flow cytometry analysis did not reveal any significant difference between WT and TgHD MSCs. Nevertheless, following differentiation into adipocytes, the expression of CEBP alpha nuclear, PPAR gamma and adipogenic marker FABP4/AP2 were significantly lower in TgHD cells compared to WT cells. In addition, we proved both rosiglitazone and indomethacin to be efficient for adipogenic differentiation of porcine MSCs, with rosiglitazone showing a better adipogenic profile. nConclusions: We demonstrated a negative influence of mtHtt on adipogenic differentiation of porcine MSCs in vitro associated with compromised expression of adipogenic transcription factors.

Název v anglickém jazyce

Adipogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells in Pig Transgenic Model Expressing Human Mutant Huntingtin

Popis výsledku anglicky

Background: Although the highest expression of mutant huntingtin (mtHtt) was observed in the brain, its negative effects were also apparent in other tissues. Specifically, mtHtt impairs metabolic homeostasis and causes transcriptional dysregulation in adipose tissue. Adipogenic differentiation can be induced by the activation of two transcription factors: CCAAT/enhancer-binding protein alpha (CEBP alpha) and peroxisome proliferator-activated receptor gamma (PPAR gamma). These same transcription factors were found to be compromised in some tissues of Huntington's disease (HD) mouse models and in lymphocytes of HD patients. nObjective: This study investigated the adipogenic potential of mesenchymal stem cells (MSCs) derived from transgenic Huntington's disease (TgHD) minipigs expressing human mtHtt (1-548aa) containing 124 glutamines. Two differentiation conditions were used, employing PPAR gamma agonist rosiglitazone or indomethacin.nMethods: Bone marrow MSCs were isolated from TgHD and WT minipig siblings and compared by their cluster of differentiation using flow cytometry. Their adipogenic potential in vitro was analyzed using quantitative immunofluorescence and western blot analysis of transcription factors and adipogenic markers. nResults: Flow cytometry analysis did not reveal any significant difference between WT and TgHD MSCs. Nevertheless, following differentiation into adipocytes, the expression of CEBP alpha nuclear, PPAR gamma and adipogenic marker FABP4/AP2 were significantly lower in TgHD cells compared to WT cells. In addition, we proved both rosiglitazone and indomethacin to be efficient for adipogenic differentiation of porcine MSCs, with rosiglitazone showing a better adipogenic profile. nConclusions: We demonstrated a negative influence of mtHtt on adipogenic differentiation of porcine MSCs in vitro associated with compromised expression of adipogenic transcription factors.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Journal of Huntington´s Disease

ISSN

1879-6397

e-ISSN

—

Svazek periodika

8

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

19

Strana od-do

33-51

Kód UT WoS článku

000458980600004

EID výsledku v databázi Scopus

2-s2.0-85061922028