TY - JOUR

T1 - Generation and Analysis of Human Induced Pluripotent Stem Cell Lines iTAF1-36-H7.1 and iTAF1-36-H7.2 with HAR Deletion in the CNTN6 Locus

AU - Knyazeva, A. S.

AU - Yunusova, A. M.

AU - Smirnov, A. V.

AU - Shnaider, T. A.

N1 - Generation and Analysis of Human Induced Pluripotent Stem Cell Lines iTAF1-36-H7.1 and iTAF1-36-H7.2 with HAR Deletion in the CNTN6 Locus / A. S. Knyazeva, A. M. Yunusova, A. V. Smirnov, T. A. Shnaider // Russian Journal of Developmental Biology. – 2025. – Vol. 56, No. 5. – P. 217-226. – DOI 10.1134/S1062360426700025. – EDN EZLQYL. The study was financially supported by the Russian Science Foundation (RSF), project no. 24-24-00447

PY - 2026/5/13

Y1 - 2026/5/13

N2 - Over the past 6–8 million years, in the evolutionary line leading to modern humans, the brain has undergone significant changes. Its volume has tripled compared to that of other great apes, and the increased structural complexity has been associated with a marked prolongation of developmental stages. The emergence of these specific morphological features is linked to profound alterations in the genetic programs regulating brain development. Changes in regulatory regions of the human genome, which can modify the spatiotemporal patterns of gene expression, have a significant impact on this evolutionary process. One of the drivers of such evolutionary changes is human accelerated regions (HARs), which represent conserved DNA regions in mammals that have acquired specific mutations in humans. The overwhelming majority of these elements are non-coding DNA sequences, localized in intronic and intergenic regions near genes essential for brain development. Genetic variants within HARs have been associated with neurodevelopmental and psychiatric disorders and are known to alter gene expression. One gene whose regulation may be influenced by HARs is CNTN6. Two HARs have been identified within its introns and frequently overlap with CNTN6 copy number variations observed in patients with neurodevelopmental disorders. To further investigate the functional role of one of these elements, HARsv2_1747, in human neurodevelopment, we used the CRISPR/Cas9 system to generate two human induced pluripotent stem cell (iPSC) lines: one with a homozygous deletion and another with a compound heterozygous deletion of this region. Both iPSC lines fulfill the key criteria for pluripotency, as they form colonies with typical pluripotent cell morphology, maintain a normal diploid karyotype, express pluripotency markers, and retain the ability to differentiate into derivatives of all three germ layers.

AB - Over the past 6–8 million years, in the evolutionary line leading to modern humans, the brain has undergone significant changes. Its volume has tripled compared to that of other great apes, and the increased structural complexity has been associated with a marked prolongation of developmental stages. The emergence of these specific morphological features is linked to profound alterations in the genetic programs regulating brain development. Changes in regulatory regions of the human genome, which can modify the spatiotemporal patterns of gene expression, have a significant impact on this evolutionary process. One of the drivers of such evolutionary changes is human accelerated regions (HARs), which represent conserved DNA regions in mammals that have acquired specific mutations in humans. The overwhelming majority of these elements are non-coding DNA sequences, localized in intronic and intergenic regions near genes essential for brain development. Genetic variants within HARs have been associated with neurodevelopmental and psychiatric disorders and are known to alter gene expression. One gene whose regulation may be influenced by HARs is CNTN6. Two HARs have been identified within its introns and frequently overlap with CNTN6 copy number variations observed in patients with neurodevelopmental disorders. To further investigate the functional role of one of these elements, HARsv2_1747, in human neurodevelopment, we used the CRISPR/Cas9 system to generate two human induced pluripotent stem cell (iPSC) lines: one with a homozygous deletion and another with a compound heterozygous deletion of this region. Both iPSC lines fulfill the key criteria for pluripotency, as they form colonies with typical pluripotent cell morphology, maintain a normal diploid karyotype, express pluripotency markers, and retain the ability to differentiate into derivatives of all three germ layers.

KW - индуцированные плюрипотентные стволовые клетки

KW - ускоренные регионы человека

KW - система CRISPR/Cas9

KW - CNTN6

KW - регуляторные последовательности

KW - induced pluripotent stem cells

KW - human accelerated regions

KW - CRISPR/Cas9 system

KW - CNTN6

KW - egulatory sequences

UR - https://www.mendeley.com/catalogue/8319607b-2b16-3998-9782-d666177f0d29/

UR - https://www.elibrary.ru/item.asp?id=90807699

U2 - 10.1134/s1062360426700025

DO - 10.1134/s1062360426700025

M3 - Article

VL - 56

SP - 217

EP - 226

JO - Russian Journal of Developmental Biology

JF - Russian Journal of Developmental Biology

SN - 1062-3604

IS - 5

ER -