by Pristyazhnyuk Inna | Shnaider Tatyana | Khabarova Anna | Morozova Kseniya | Kiseleva Elena |
Vladimirova Elena | Chechetkina Sophia | Chvileva Anastasia | Smirnova Anna | Larina D. | Institute of
Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS,
Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of
Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS,
Novosibirsk, Russia | Novosibirsk State University, Novosibirsk, Russia | Novosibirsk State University,
Novosibirsk, Russia | Novosibirsk State University, Novosibirsk, Russia | Laboratory of clinical genomics
and bioinformatics, Research and Clinical Institute for Pediatrics named after Academician Yuri
Veltischev, Moscow | Laboratory of clinical genomics and bioinformatics, Research and Clinical Institute
for Pediatrics named after Academician Yuri Veltischev, Moscow
Cohen’s syndrome (CS) is an autosomal recessive disorder caused by mutations in the COH1
(VPS13B) gene. CS is characterized by growth and mental retardation, microcephaly, and
the development of autism spectrum disorders.
The COH1 protein is one of the key participants of the intracellular membrane transport
system, the central part of which is the Golgi apparatus (GA). Recent studies have shown
that mutations affecting GA proteins also result in the postnatal microcephaly associated
diseases. GA is extremely important for the differentiation and functioning of postmitotic
neurons. It plays a major role in determining and creating the cellular polarity necessary for
the formation of highly specialized neurites – axons and dendrites.
The product of the COH1 gene is a peripheral membrane protein localized in GA and
contributes to the structural maintenance and functioning of this complex. The supposed
function of the COH1 protein is the regulation of vesicular transport and intracellular
protein sorting.
We have obtained the iPSC cell lines from the biopsy material of two patients with
compound heterozygous mutations in the COH1 gene. The iPSC lines from both patients
have morphology of pluripotent cell, normal karyotype (46,XX), express pluripotency
markers (OCT4, NANOG), and surface markers SSEA-1 and TRA-1-60. During differentiation
in embryoid bodies, they contribute to three germ layers (ectoderm, mesoderm, and
endoderm). These iPSC lines will serve as the basis for studying the pathology of cortical
neurons formation in CS patients.
There using will allow us to study the later stages of neurogenesis, in particular neuritogenesis, axons and dendrites formation, as well as the features of the structural
organization of the GA and vesicular transport in the cell. By studying the effect of
mutations in the COH1 gene that cause CS, we will be able to establish the role of this gene
in the process of normal human neurogenesis