MicroRNA alterations in iPSC-derived dopaminergic neurons from Parkinson disease patients

Autor: Raquel Ferrer-Lorente, Mario Ezquerra, María-José Martí, Manel Fernández, Teresa Botta-Orfila, Carles Calatayud, Rubén Fernández-Santiago, Xavier Morató, Antonella Consiglio, Eduard Tolosa, Angel Raya, Carles Gaig
Rok vydání: 2018
Předmět:
Adult
Male
0301 basic medicine
Aging
Induced Pluripotent Stem Cells
Down-Regulation
Gene Expression
Biology
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
microRNA (miRNA)
03 medical and health sciences
Parkinson disease (PD)
Neural Stem Cells
Downregulation and upregulation
Dopaminergic neuron (DAn)
microRNA
Humans
Epigenetics
Induced pluripotent stem cell
Transcription factor
Aged
Transcription factor (TF)
Dopaminergic Neurons
Gene Expression Profiling
General Neuroscience
Dopaminergic
Cell Differentiation
Parkinson Disease
Middle Aged
Up-Regulation
Dopaminergic neuron (DAn)
Leucine-rich repeat kinase 2 (LRRK2)
Parkinson disease (PD)
Transcription factor (TF)
microRNA (miRNA)
MicroRNAs
Leucine-rich repeat kinase 2 (LRRK2)
Female
030104 developmental biology
Cancer research
Neurology (clinical)
Geriatrics and Gerontology
FOXA1
Reprogramming
Developmental Biology
Zdroj: NEUROBIOLOGY OF AGING
r-FSJD: Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
Fundació Sant Joan de Déu
r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname
ISSN: 0197-4580
DOI: 10.1016/j.neurobiolaging.2018.05.032
Popis: MicroRNA (miRNA) misregulation in peripheral blood has been linked to Parkinson disease (PD) but its role in the disease progression remains elusive. We performed an explorative genome-wide study of miRNA expression levels in dopaminergic neurons (DAn) from PD patients generated by somatic cell reprogramming and induced pluripotent stem cells differentiation. We quantified expression levels of 377 miRNAs in DAn from 3 sporadic PD patients (sPD), 3 leucine-rich repeat kinase 2-associated PD patients (L2PD) (total 6 PD), and 4 healthy controls. We identified differential expression of 10 miRNA of which 5 were upregulated in PD (miR-9-5p, miR-135a-5p, miR-135b-5p, miR-449a, and miR-449b-5p) and 5 downregulated (miR-141-3p, miR-199a-5p, miR-299-5p, miR-518e-3p, and miR-519a-3p). Changes were similar in sPD and L2PD. Integrative analysis revealed significant correlations between miRNA/mRNA expression. Moreover, upregulation of miR-9-5p and miR-135b-5p was associated with downregulation of transcription factors related to the DNA hypermethylation of enhancer elements in PD DAn (FOXA1 and NR3C1). In summary, miRNA changes are associated with monogenic L2PD and sPD and co-occur with epigenetic changes in DAn from PD patients.
Databáze: OpenAIRE
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