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

Result code in 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>

Alternative codes found

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

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

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

Publication year

2019

Confidentiality

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

Name of the periodical

Journal of Huntington´s Disease

ISSN

1879-6397

e-ISSN

—

Volume of the periodical

8

Issue of the periodical within the volume

1

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

19

Pages from-to

33-51

UT code for WoS article

000458980600004

EID of the result in the Scopus database

2-s2.0-85061922028