TY - JOUR

T1 - Identification of specific gene methylation patterns during motor neuron differentiation from spinal muscular atrophy patient-derived iPSC

AU - Maretina, M. A.

AU - Valetdinova, K. R.

AU - Tsyganova, N. A.

AU - Egorova, A. A.

AU - Ovechkina, V. S.

AU - Schiöth, H. B.

AU - Zakian, S. M.

AU - Baranov, V. S.

AU - Kiselev, A. V.

N1 - Funding Information: This work was supported by Russian Foundation for Basic Research grant 18-315-00258 and by Ministry of Science and Higher Education of the Russian Federation , project number AAAA-A19-119021290033-1 . We also acknowledge partial financial support of DNA bisulfite conversion reagents by Saint-Petersburg City Administration grant for young scientists. Marianna A. Maretina is supported by the President of Russian Federation scholarship ( SP-822.2018.4 ). Helgi B. Schiöth is supported by the Swedish Research Council . Publisher Copyright: © 2021 Elsevier B.V.

PY - 2022/2/15

Y1 - 2022/2/15

N2 - Spinal muscular atrophy is a progressive motor neuron disorder caused by deletions or point mutations in the SMN1 gene. It is not known why motor neurons are particularly sensitive to a decrease in SMN protein levels and what factors besides SMN2 underlie the high clinical heterogeneity of the disease. Here we studied the methylation patterns of genes on sequential stages of motor neuron differentiation from induced pluripotent stem cells derived from the patients with SMA type I and II. The genes involved in the regulation of pluripotency, neural differentiation as well as those associated with spinal muscular atrophy development were included. The results show that the PAX6, HB9, CHAT, ARHGAP22, and SMN2 genes are differently methylated in cells derived from SMA patients compared to the cells of healthy individuals. This study clarifies the specificities of the disease pathogenesis and extends the knowledge of pathways involved in the SMA progression.

AB - Spinal muscular atrophy is a progressive motor neuron disorder caused by deletions or point mutations in the SMN1 gene. It is not known why motor neurons are particularly sensitive to a decrease in SMN protein levels and what factors besides SMN2 underlie the high clinical heterogeneity of the disease. Here we studied the methylation patterns of genes on sequential stages of motor neuron differentiation from induced pluripotent stem cells derived from the patients with SMA type I and II. The genes involved in the regulation of pluripotency, neural differentiation as well as those associated with spinal muscular atrophy development were included. The results show that the PAX6, HB9, CHAT, ARHGAP22, and SMN2 genes are differently methylated in cells derived from SMA patients compared to the cells of healthy individuals. This study clarifies the specificities of the disease pathogenesis and extends the knowledge of pathways involved in the SMA progression.

KW - DNA methylation

KW - Genetic modifier

KW - iPSC

KW - Neuronal differentiation

KW - SMN

KW - Spinal muscular atrophy

KW - Humans

KW - Cells, Cultured

KW - Neurogenesis

KW - Induced Pluripotent Stem Cells/physiology

KW - DNA Methylation

KW - Muscular Atrophy, Spinal/genetics

KW - Survival of Motor Neuron 2 Protein/genetics

KW - Gene Expression Regulation, Developmental

KW - GTPase-Activating Proteins/genetics

KW - Motor Neurons/physiology

KW - PAX6 Transcription Factor/genetics

KW - Survival of Motor Neuron 1 Protein/genetics

KW - Cell Differentiation

UR - http://www.scopus.com/inward/record.url?scp=85120678863&partnerID=8YFLogxK

U2 - 10.1016/j.gene.2021.146109

DO - 10.1016/j.gene.2021.146109

M3 - Article

C2 - 34871761

AN - SCOPUS:85120678863

VL - 811

JO - Gene

JF - Gene

SN - 0378-1119

M1 - 146109

ER -