Irina Neganova

Institute of Cytology

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Majlinda Lako

Newcastle University

Anvar Shukurov

Newcastle University

N. G. Parker

Newcastle University

Laura E Wadkin

Newcastle University

Sirio Orozco-Fuentes

Newcastle University

Olga Krasnova

Institute of Cytology

Lyle Armstrong

Newcastle University

Julia V. Sopova

Institute of Cytology

Vitaly V. Gursky

Ioffe Institute

Rafael A. Barrio

Universidad Nacional Autónoma de México

Cooperative Institutions

Newcastle University

Institute of Cytology

Centre for Life

StemCells (United States)

Russian Academy of Sciences

St Petersburg University

University of Newcastle Australia

Imperial College London

Centro de Investigacion Principe Felipe

Ministry of Health of the Russian Federation

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An introduction to the mathematical modeling of iPSCs

Elsevier eBooks (2021)

Laura E Wadkin Sirio Orozco-Fuentes Irina Neganova Majlinda Lako N. G. Parker

10.1016/b978-0-12-822231-7.00004-7

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Citations (0)

Derivation of hiPSC line (ICADRB2i007-A-3) from an individual with osteoporosis linked to ADRB2: c.46G > A

Human Cell (2025)

Olga Krasnova Polina Semenova Anastasia Kovaleva Julia V. Sopova В. И. Турилова

Line (geometry)

10.1007/s13577-025-01180-4

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The recent advances in the mathematical modelling of human pluripotent stem cells

arXiv (Cornell University) (2019)

Laura E Wadkin Sirio Orozco-Fuentes Irina Neganova Majlinda Lako Anvar Shukurov

Human pluripotent stem cells hold great promise for developments in regenerative medicine and drug design. The mathematical modelling of stem cells and their properties is necessary to understand and quantify key behaviours and develop non-invasive prognostic modelling tools to assist in the optimisation of laboratory experiments. Here, the recent advances in the mathematical modelling of hPSCs are discussed, including cell kinematics, cell proliferation and colony formation, and pluripotency and differentiation.

Regenerative Medicine

10.48550/arxiv.1909.10344

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A role for NANOG in G1 to S transition in human embryonic stem cells through direct binding of CDK6 and CDC25A

The Journal of Cell Biology (2009)

Xin Zhang Irina Neganova Stefan Przyborski Chunbo Yang Michael J. Cooke

In this study, we show that NANOG, a master transcription factor, regulates S-phase entry in human embryonic stem cells (hESCs) via transcriptional regulation of cell cycle regulatory components. Chromatin immunoprecipitation combined with reporter-based transfection assays show that the C-terminal region of NANOG binds to the regulatory regions of CDK6 and CDC25A genes under normal physiological conditions. Decreased CDK6 and CDC25A expression in hESCs suggest that both CDK6 and CDC25A are involved in S-phase regulation. The effects of NANOG overexpression on S-phase regulation are mitigated by the down-regulation of CDK6 or CDC25A alone. Overexpression of CDK6 or CDC25A alone can rescue the impact of NANOG down-regulation on S-phase entry, suggesting that CDK6 and CDC25A are downstream cell cycle effectors of NANOG during the G1 to S transition.

Homeobox protein NANOG

Cyclin-dependent kinase 6

Nanog Homeobox Protein

Chromatin immunoprecipitation

Rex1

10.1083/jcb.200801009

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Citations (185)

Role of G protein-associated membrane receptors in the pathogenesis of osteoporosis

Translational Medicine (2022)

А. П. Домнина Olga Krasnova K. A. Kulakova Julia V. Sopova V. V. Karelkin

Osteoporosis is a chronic disease characterized by a pathological change in bone tissue, excessive fragility and a decrease in bone strength as a result of the predominance of bone resorption processes over the process of bone formation. This disease manifests in the form of low-traumatic fractures occurring in result of falling from a height of one’s height, or with little physical exertion. Osteoporosis could result in the fractures of the vertebral bodies and bones of the peripheral skeleton, causing a high level of disability. Of note, postmenopausal osteoporosis develops in women against the background of the cessation of the menstrual cycle. Here we overview the role of G-protein-associated membrane receptors (GPCR family) in the pathogenesis of this disease and the prospects for finding targets among these receptors for the diagnosis and treatment of osteoporosis. Malformations in the genes encoding GPCR lead to impaired bone tissue remodeling. Exploring the functions of GPCR family members is critical to the search for predisposition markers of bone tissue dysfunction and could improve the early diagnosis of osteoporosis. Studies on a model of osteoblasts differentiated from hIPSCs obtained from patients with osteoporosis associated with mutations in the genes of the GPCR family will allow a deeper understanding of the molecular nature of osteoporosis and the identification of new targets for osteoporosis treatment.

Bone remodeling

Pathogenesis

Bone disease

10.18705/2311-4495-2022-9-4-41-61

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Citations (3)

Dynamics of single human embryonic stem cells and their pairs: a quantitative analysis

Scientific Reports (2017)

Laura E Wadkin L. F. Elliot Irina Neganova N. G. Parker Valeria Chichagova

Abstract Numerous biological approaches are available to characterise the mechanisms which govern the formation of human embryonic stem cell (hESC) colonies. To understand how the kinematics of single and pairs of hESCs impact colony formation, we study their mobility characteristics using time-lapse imaging. We perform a detailed statistical analysis of their speed, survival, directionality, distance travelled and diffusivity. We confirm that single and pairs of cells migrate as a diffusive random walk for at least 7 hours of evolution. We show that the presence of Cell Tracer significantly reduces hESC mobility. Our results open the path to employ the theoretical framework of the diffusive random walk for the prognostic modelling and optimisation of the growth of hESC colonies. Indeed, we employ this random walk model to estimate the seeding density required to minimise the occurrence of hESC colonies arising from more than one founder cell and the minimal cell number needed for successful colony formation. Our prognostic model can be extended to investigate the kinematic behaviour of somatic cells emerging from hESC differentiation and to enable its wide application in phenotyping of pluripotent stem cells for large scale stem cell culture expansion and differentiation platforms.

Dynamics

10.1038/s41598-017-00648-0

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Citations (19)

SNPs in GPCR Genes and Impaired Osteogenic Potency in Osteoporotic Patient Lines-Based Study

International Journal of Molecular Sciences (2024)

Julia V. Sopova Olga Krasnova G. I. Vasilieva Anna S. Zhuk O. M. Lesnyak

G-protein-coupled receptors (GPCRs) have emerged as critical regulators of bone development and remodeling. In this study, we aimed to identify specific GPCR mutations in osteoporotic patients via next-generation sequencing (NGS). We performed NGS sequencing of six genomic DNA samples taken from osteoporotic patients and two genomic DNA samples from healthy donors. Next, we searched for single-nucleotide polymorphisms (SNPs) in GPCR genes that are associated with osteoporosis. For three osteoporotic patients and one healthy donor, bone biopsies were used to generate patient-specific mesenchymal stem cell (MSC) lines, and their ability to undergo osteodifferentiation was analyzed. We found that MSCs derived from osteoporotic patients have a different response to osteoinductive factors and impaired osteogenic differentiation using qPCR and histochemical staining assays. The NGS analysis revealed specific combinations of SNPs in GPCR genes in these patients, where SNPs in ADRB2 (rs1042713), GIPR (rs1800437), CNR2 (rs2501431, rs3003336), and WLS (rs3762371) were associated with impaired osteogenic differentiation capacity. By integrating NGS data with functional assessments of patient-specific cell lines, we linked GPCR mutations to impaired bone formation, providing a foundation for developing personalized therapeutic strategies. SNP analysis is recognized as a proactive approach to osteoporosis management, enabling earlier interventions and targeted preventive measures for individuals at risk. Furthermore, SNP analysis contributes to the development of robust, holistic risk prediction models that enhance the accuracy of risk assessments across the population. This integration of genetic data into public health strategies facilitates healthcare initiatives. This approach could guide treatment decisions tailored to the patient’s genetic profile and provide a foundation for developing personalized therapeutic strategies.

SNP

Pharmacogenomics

10.3390/ijms252413594

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Modulation of Notch Signaling at Early Stages of Differentiation of Human Induced Pluripotent Stem Cells to Dopaminergic Neurons

International Journal of Molecular Sciences (2023)

Nataliia V. Katolikova Aleksandr Khudiakov Daria D. Shafranskaya Andrey D. Prjibelski Alexey E. Masharskiy

Elaboration of protocols for differentiation of human pluripotent stem cells to dopamine neurons is an important issue for development of cell replacement therapy for Parkinson's disease. A number of protocols have been already developed; however, their efficiency and specificity still can be improved. Investigating the role of signaling cascades, important for neurogenesis, can help to solve this problem and to provide a deeper understanding of their role in neuronal development. Notch signaling plays an essential role in development and maintenance of the central nervous system after birth. In our study, we analyzed the effect of Notch activation and inhibition at the early stages of differentiation of human induced pluripotent stem cells to dopaminergic neurons. We found that, during the first seven days of differentiation, the cells were not sensitive to the Notch inhibition. On the contrary, activation of Notch signaling during the same time period led to significant changes and was associated with an increase in expression of genes, specific for caudal parts of the brain, a decrease of expression of genes, specific for forebrain, as well as a decrease of expression of genes, important for the formation of axons and dendrites and microtubule stabilizing proteins.

Forebrain

Hes3 signaling axis

10.3390/ijms24021429

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Citations (5)

LacZ transgene expression as a cell marker to analyse rescue from the 2-cell block in mouse aggregation chimeras

Zygote (1998)

Irina Neganova Martin Augustin Galina G. Sekirina Harald Jockusch

Embryos from certain mouse strains are arrested at the 2-cell stage in cell culture (‘2-cell block’), whereas those from other strains develop to the blastocyst stage under the same conditions. It was previously shown that blocking embryos can be rescued in culture by aggregation with an excess of 2-cell stages of a non-blocking strain such as CBA × C57BL/6 F 2 . Here we have employed a LacZ transgene in a blocking strain (NMRI) to follow the fate of rescued blastomeres up to the blastocyst stage. We found that rescued blastomeres can participate in both inner cell mass and trophoblast formation, thus completely overcoming the 2-cell block.

Blastomere

Inner cell mass

Trophoblast

10.1017/s096719949800015x

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Citations (8)

Expression and functional analysis of G1 to S regulatory components reveals an important role for CDK2 in cell cycle regulation in human embryonic stem cells

Oncogene (2008)

Irina Neganova X Zhang Stuart P. Atkinson Majlinda Lako

Cyclin-dependent kinase 6

Restriction point

Cyclin A

10.1038/onc.2008.358

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Citations (181)