Activation of Embryonic Gene Transcription in Neural Precursor Cells Derived from the Induced Pluripotent Stem Cells of the Patients with Parkinson's Disease

被引:0
作者
Fedoseyeva, Viya B. [1 ]
Novosadova, Ekaterina V. [1 ]
Nenasheva, Valentina V. [1 ]
Novosadova, Lyudmila V. [1 ]
Grivennikov, Igor A. [1 ]
Tarantul, Vyacheslav Z. [1 ]
机构
[1] Natl Res Ctr Kurchatov Inst, Moscow 123182, Russia
基金
俄罗斯科学基金会;
关键词
Parkinson's disease; induced pluripotent stem cells; neural precursors; RNA-seq; differential gene expression; PCR; bioinformatic analysis; RETINOIC ACID; SYSTEM-DEVELOPMENT; EXPRESSION; MIDBRAIN; DIFFERENTIATION; HINDBRAIN; MIGRATION; NEURONS; BINDING; ASCL1;
D O I
10.1134/S0006297923040077
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Parkinson's disease (PD) is one of the most common neurodegenerative diseases in the world. Despite numerous studies, the causes of this pathology remain completely unknown. This is, among other things, due to the difficulty of obtaining biological material for analysis. Neural cell cultures derived from the induced pluripotent stem cells (IPSCs) provide a great potential for studying molecular events underlying the pathogenesis of PD. This paper presents the results of bioinformatic analysis of the data obtained using RNA-seq technology in the study of neural precursors (NP) derived from IPSCs of the healthy donors and patients with PD carrying various mutations that are commonly associated with familial PD. This analysis showed that the level of transcription of multiple genes actively expressed in the nervous system at the embryonic stage of development was significantly increased in the NP cells obtained from the patients with PD, unlike in the case of healthy donors. Bioinformatic data have been, in general, confirmed using real-time PCR. The obtained data suggest that one of the causes of PD may be the shift of the gene expression pattern in neuronal cells towards embryonic gene expression pattern (termed dematuration).
引用
收藏
页码:515 / 525
页数:11
相关论文
共 69 条
[1]   Genetic and physical interaction of Meis2, Pax3 and Pax7 during dorsal midbrain development [J].
Agoston, Zsuzsa ;
Li, Naixin ;
Haslinger, Anja ;
Wizenmann, Andrea ;
Schulte, Dorothea .
BMC DEVELOPMENTAL BIOLOGY, 2012, 12
[2]   Meis2 competes with the Groucho co-repressor Tle4 for binding to Otx2 and specifies tectal fate without induction of a secondary midbrain-hindbrain boundary organizer [J].
Agoston, Zsuzsa ;
Schulte, Dorothea .
DEVELOPMENT, 2009, 136 (19) :3311-3322
[3]   Comprehensive transcriptome analysis of differentiation of embryonic stem cells into midbrain and hindbrain neurons [J].
Ahn, JI ;
Lee, KH ;
Shin, DM ;
Shim, JW ;
Lee, JS ;
Chang, SY ;
Lee, YS ;
Brownstein, MJ ;
Lee, SH ;
Lee, YS .
DEVELOPMENTAL BIOLOGY, 2004, 265 (02) :491-501
[4]   Gene expression profile of brain regions reflecting aberrations in nervous system development targeting the process of neurite extension of rat offspring exposed developmentally to glycidol [J].
Akane, Hirotoshi ;
Saito, Fumiyo ;
Shiraki, Ayako ;
Imatanaka, Nobuya ;
Akahori, Yumi ;
Itahashi, Megu ;
Wang, Liyun ;
Shibutani, Makoto .
JOURNAL OF APPLIED TOXICOLOGY, 2014, 34 (12) :1389-1399
[5]  
Ang SL, 2009, ADV EXP MED BIOL, V651, P58
[7]   ASCL1 is a lineage oncogene providing therapeutic targets for high-grade neuroendocrine lung cancers [J].
Augustyn, Alexander ;
Borromeo, Mark ;
Wang, Tao ;
Fujimoto, Junya ;
Shao, Chunli ;
Dospoy, Patrick D. ;
Lee, Victoria ;
Tan, Christopher ;
Sullivan, James P. ;
Larsen, Jill E. ;
Girard, Luc ;
Behrens, Carmen ;
Wistuba, Ignacio I. ;
Xie, Yang ;
Cobb, Melanie H. ;
Gazdar, Adi F. ;
Johnson, Jane E. ;
Minna, John D. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (41) :14788-14793
[8]   Modelling Parkinson's Disease: iPSCs towards Better Understanding of Human Pathology [J].
Avazzadeh, Sahar ;
Baena, Jara Maria ;
Keighron, Cameron ;
Feller-Sanchez, Yajaira ;
Quinlan, Leo R. .
BRAIN SCIENCES, 2021, 11 (03)
[9]   Hes5 regulates the transition timing of neurogenesis and gliogenesis in mammalian neocortical development [J].
Bansod, Shama ;
Kageyama, Ryoichiro ;
Ohtsuka, Toshiyuki .
DEVELOPMENT, 2017, 144 (17) :3156-3167
[10]   LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6 [J].
Berwick, Daniel C. ;
Harvey, Kirsten .
HUMAN MOLECULAR GENETICS, 2012, 21 (22) :4966-4979