Pluripotent stem cell-based gene therapy approach: human de novo synthesized chromosomes

Sinenko, Sergey; Ponomartsev, Sergey V.; Tomilin, Alexey

doi:10.1007/s00018-020-03653-1

Cited by 14 publications

(13 citation statements)

References 121 publications

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“…Embryonic stem cells (ESCs) originate from the inner cell mass of the mammalian blastocyst and possess the ability to self-renew and differentiate into all cell types of an adult organism. All pluripotent stem cells (PSCs), including ESCs, have an enormous potential of applications in cell therapy and modeling human diseases, thus making investigation on the molecular network regulating their maintenance, including metabolism pathways and redox signaling, of great importance (Murry and Keller, 2008;Yamanaka, 2020;Sinenko et al, 2021). ESCs and other PSCs have a high proliferation rate due to a shortened G1 cell cycle phase, which requires a high supply for anabolic precursors necessary for genome and cell replication.…”

Section: Ros Function In Embryonic Stem Cellsmentioning

confidence: 99%

Physiological Signaling Functions of Reactive Oxygen Species in Stem Cells: From Flies to Man

Sinenko

Starkova

Kuzmin

et al. 2021

Front. Cell Dev. Biol.

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136

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Reactive oxygen species (ROS), superoxide anion and hydrogen peroxide, are generated as byproducts of oxidative phosphorylation in the mitochondria or via cell signaling-induced NADPH oxidases in the cytosol. In the recent two decades, a plethora of studies established that elevated ROS levels generated by oxidative eustress are crucial physiological mediators of many cellular and developmental processes. In this review, we discuss the mechanisms of ROS generation and regulation, current understanding of ROS functions in the maintenance of adult and embryonic stem cells, as well as in the process of cell reprogramming to a pluripotent state. Recently discovered cell-non-autonomous ROS functions mediated by growth factors are crucial for controlling cell differentiation and cellular immune response in Drosophila. Importantly, many physiological functions of ROS discovered in Drosophila may allow for deciphering and understanding analogous processes in human, which could potentially lead to the development of novel therapeutic approaches in ROS-associated diseases treatment.

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Section: Ros Function In Embryonic Stem Cellsmentioning

confidence: 99%

Physiological Signaling Functions of Reactive Oxygen Species in Stem Cells: From Flies to Man

Sinenko

Starkova

Kuzmin

et al. 2021

Front. Cell Dev. Biol.

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136

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“…Второй подход -синтетический, «снизу-вверх» (англ. bottom-up) -позволяет получать линейные или кольцевые ИХЧ посредством синтеза и сборки больших участков прицентромерной альфа-сателлитной ДНК in vitro [13,[17][18][19]. Необходимо отметить, что, несмотря на очевидные преимущества ИХЧ перед другими векторными системами, существует ряд технических ограничений для их активного использования как в научных исследованиях, так и в биомедицинских приложениях.…”

Section: рефератunclassified

“…Клонирование таких последовательностей крайне затруднительно из-за спонтанной рекомбинации [42]. Первая успешная попытка С помощью альфоидных tetO -ИХЧ в клетки-мишени перенесли полноразмерные гены, содержащие свои цис-регуляторные последовательности, а затем показали стабильную экспрессию этих генов [19,[54][55][56]. В проведенных нами исследованиях GFP-экспрессирующие альфоидные tetO -ИХЧ были перенесены в ЭСК мыши.…”

Section: альфоидные ихчunclassified

Human Artificial Chromosomes and Their Transfer to Target Cells

2022

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Human artificial chromosomes (HACs) have been developed as genetic vectors with the capacity to carry large transgenic constructs or entire gene loci. HACs represent either truncated native chromosomes or de novo synthesized genetic constructs. The important features of HACs are their ultra-high capacity and ability to self-maintain as independent genetic elements, without integrating into host chromosomes. In this review, we discuss the development and construction methods, structural and functional features, as well as the areas of application of the main HAC types. Also, we address one of the most technically challenging and time-consuming steps in this technology the transfer of HACs from donor to recipient cells.

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“…Moreover, these cells overcome ethical issues associated with isolating human ESCs from blastocysts. Therefore, iPSCs have revolutionized the field of personalized medical research, including in vitro disease modeling, drug screening, and regenerative cell therapy [ 10 , 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

PAX9 Is Involved in Periodontal Ligament Stem Cell-like Differentiation of Human-Induced Pluripotent Stem Cells by Regulating Extracellular Matrix

et al. 2022

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Periodontal ligament stem cells (PDLSCs) play central roles in periodontal ligament (PDL) tissue homeostasis, repair, and regeneration. Previously, we established a protocol to differentiate human-induced pluripotent stem cell-derived neural crest-like cells (iNCs) into PDLSC-like cells (iPDLSCs) using human PDL cell-derived extracellular matrix (ECM). However, it remained unclear what factors principally regulate the differentiation of iNCs into iPDLSCs. In this study, we aimed to identify the transcription factor regulating production of human PDL cell-derived ECM, which is responsible for the generation of iPDLSCs. We cultured iNCs on ECMs of two human PDL cell lines (HPDLC-3S and HPDLC-3U) and of human dermal fibroblasts (HDF). iNCs cultured on HPDLC-3U demonstrated higher iPDLSC-associated gene expression and mesenchymal differentiation capacity than cells cultured on HDF or HPDLC-3S. The transcription factor PAX9 was highly expressed in HPDLC-3U compared with HDF and HPDLC-3S. iNCs cultured on siPAX9-transfected HPDLC-3U displayed downregulation of iPDLSC-associated marker expression and adipocytic differentiation capacity relative to controls. Our findings suggest that PAX9 is one of the transcription factors regulating ECM production in human PDL cells, which is responsible for the differentiation of iNCs into iPDLSCs.

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Pluripotent stem cell-based gene therapy approach: human de novo synthesized chromosomes

Cited by 14 publications

References 121 publications

Physiological Signaling Functions of Reactive Oxygen Species in Stem Cells: From Flies to Man

Physiological Signaling Functions of Reactive Oxygen Species in Stem Cells: From Flies to Man

Human Artificial Chromosomes and Their Transfer to Target Cells

PAX9 Is Involved in Periodontal Ligament Stem Cell-like Differentiation of Human-Induced Pluripotent Stem Cells by Regulating Extracellular Matrix

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