Neural differentiation of patient-specific induced pluripotent stem cells from patients with a hereditary form of spinal muscular atrophy



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Abstract

Induced pluripotent stem cells (iPSCs) give the possibility for disease modeling, drug and toxicology screening and development of the new therapeutic approaches. Directed differentiation of iPSCs into specialized cell types represents a unique tool in order to study and model certain diseases, which affects specific type of cells, in vitro. One of the typical example of such diseases is spinal muscular atrophy, which is caused by mutations in the SMN1 gene (survival motor neuron 1 gene), leading to selective death of motor neurons. Patient-specific iPSCs were derived from the patient with a hereditary form of spinal muscular atrophy I type and expressed the markers of pluripotency (NANOG, TRA-1-60, SSEA4, OCT4, KLF4, MYC, REX1, and others). Spontaneous differentiation of the obtained cells resulted in the appearance of derivatives of the three germ layers: ecto-, meso- and endoderm. Neural differentiation showed the appearance of the early neural markers (PAX6, SOX2, NESTIN, TuJ1, PSA-NCAM), the late mature neural markers (MAP2, NF200, GFAP), and the mature motor neurons' markers (ISL1 and CHAT). Neurons derived from patient-specific iPSCs are perspective model for studying the features of the cells, which are altered in spinal muscular atrophy.

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About the authors

E. V Grigor'eva

Federal Research Center Institute of Cytology and Genetics, the Siberian Branch of the Russian Academy of Sciences; Institute of Chemical Biology and Fundamental Medicine, the Siberian Branch of the Russian Academy of Sciences; State Research Institute of Circulation Pathology, Ministry of Healthcare of the Russian Federation

Novosibirsk, Russia

K. R Valetdinova

Federal Research Center Institute of Cytology and Genetics, the Siberian Branch of the Russian Academy of Sciences; Institute of Chemical Biology and Fundamental Medicine, the Siberian Branch of the Russian Academy of Sciences; State Research Institute of Circulation Pathology, Ministry of Healthcare of the Russian Federation

Novosibirsk, Russia

E. I Ustyantseva

Federal Research Center Institute of Cytology and Genetics, the Siberian Branch of the Russian Academy of Sciences; Institute of Chemical Biology and Fundamental Medicine, the Siberian Branch of the Russian Academy of Sciences; State Research Institute of Circulation Pathology, Ministry of Healthcare of the Russian Federation

Novosibirsk, Russia

A. I Shevchenko

Federal Research Center Institute of Cytology and Genetics, the Siberian Branch of the Russian Academy of Sciences; Institute of Chemical Biology and Fundamental Medicine, the Siberian Branch of the Russian Academy of Sciences; State Research Institute of Circulation Pathology, Ministry of Healthcare of the Russian Federation

Novosibirsk, Russia

S. P Medvedev

Federal Research Center Institute of Cytology and Genetics, the Siberian Branch of the Russian Academy of Sciences; Institute of Chemical Biology and Fundamental Medicine, the Siberian Branch of the Russian Academy of Sciences; State Research Institute of Circulation Pathology, Ministry of Healthcare of the Russian Federation; National Research University Novosibirsk State University

Novosibirsk, Russia

N. A Mazurok

Federal Research Center Institute of Cytology and Genetics, the Siberian Branch of the Russian Academy of Sciences; Institute of Chemical Biology and Fundamental Medicine, the Siberian Branch of the Russian Academy of Sciences; State Research Institute of Circulation Pathology, Ministry of Healthcare of the Russian Federation

Novosibirsk, Russia

M. A Maretina

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott; Saint-Petersburg State University

Saint-Petersburg, Russia

M. L Kuranova

Institute of Cytology of the Russian Academy of Science

Saint-Petersburg, Russia

A. V Kiselev

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Saint-Petersburg, Russia

V. S Baranov

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott; Saint-Petersburg State University

Saint-Petersburg, Russia

S. M Zakian

Federal Research Center Institute of Cytology and Genetics, the Siberian Branch of the Russian Academy of Sciences; Institute of Chemical Biology and Fundamental Medicine, the Siberian Branch of the Russian Academy of Sciences; State Research Institute of Circulation Pathology, Ministry of Healthcare of the Russian Federation; National Research University Novosibirsk State University

Email: zakian@bionet.nsc.ru
Novosibirsk, Russia

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