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      Endogenous retroviral ERVH48-1 promotes human urine cell reprogramming

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          Abstract

          Endogenous retroviruses (ERVs), once thought to be mere remnants of ancient viral integrations in the mammalian genome, are now recognized for their critical roles in various physiological processes, including embryonic development, innate immunity, and tumorigenesis. Their impact on host organisms is significant driver of evolutionary changes, offering insight into evolutionary mechanisms. In our study, we explored the functionality of ERVs by examining single-cell transcriptomic profiles from human embryonic stem cells and urine cells. This led to the discovery of a unique ERVH48-1 expression pattern between these cell types. Additionally, somatic cell reprogramming efficacy was enhanced when ERVH48-1 was overexpressed in a urine cell-reprogramming system. Induced pluripotent stem cells (iPSCs) generated with ERVH48-1 overexpression recapitulated the traits of those produced by traditional reprogramming approaches, and the resulting iPSCs demonstrated the capability to differentiate into all three germ layers in vitro. Our research elucidated the role of ERVs in somatic cell reprogramming.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13619-024-00200-2.

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          Most cited references42

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          Induced pluripotent stem cell lines derived from human somatic cells.

          Somatic cell nuclear transfer allows trans-acting factors present in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state. We show that four factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells. These induced pluripotent human stem cells have normal karyotypes, express telomerase activity, express cell surface markers and genes that characterize human ES cells, and maintain the developmental potential to differentiate into advanced derivatives of all three primary germ layers. Such induced pluripotent human cell lines should be useful in the production of new disease models and in drug development, as well as for applications in transplantation medicine, once technical limitations (for example, mutation through viral integration) are eliminated.
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            Initial sequencing and comparative analysis of the mouse genome.

            The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.
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              Pioneer transcription factors target partial DNA motifs on nucleosomes to initiate reprogramming.

              Pioneer transcription factors (TFs) access silent chromatin and initiate cell-fate changes, using diverse types of DNA binding domains (DBDs). FoxA, the paradigm pioneer TF, has a winged helix DBD that resembles linker histone and thereby binds its target sites on nucleosomes and in compacted chromatin. Herein, we compare the nucleosome and chromatin targeting activities of Oct4 (POU DBD), Sox2 (HMG box DBD), Klf4 (zinc finger DBD), and c-Myc (bHLH DBD), which together reprogram somatic cells to pluripotency. Purified Oct4, Sox2, and Klf4 proteins can bind nucleosomes in vitro, and in vivo they preferentially target silent sites enriched for nucleosomes. Pioneer activity relates simply to the ability of a given DBD to target partial motifs displayed on the nucleosome surface. Such partial motif recognition can occur by coordinate binding between factors. Our findings provide insight into how pioneer factors can target naive chromatin sites.

                Author and article information

                Contributors
                lidongwei@gzhmu.edu.cn
                Journal
                Cell Regen
                Cell Regen
                Cell Regeneration
                Springer Nature Singapore (Singapore )
                2045-9769
                13 September 2024
                13 September 2024
                December 2024
                : 13
                : 17
                Affiliations
                [1 ]Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, ( https://ror.org/00z0j0d77) Guangzhou, 510799 China
                [2 ]GRID grid.508040.9, ISNI 0000 0004 9415 435X, Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), ; Guangzhou, 510005 China
                [3 ]GRID grid.428926.3, ISNI 0000 0004 1798 2725, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Institutes of Biomedicine and Health, , GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, Hong Kong Institute of Science & Innovation, Guangzhou, ; Guangzhou, Guangdong 510530 China
                [4 ]State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, ( https://ror.org/01r4q9n85) Macao, China
                [5 ]Guangzhou National Laboratory, Guangzhou, China
                [6 ]Laboratory of Cell Fate Control, School of Life Sciences, Westlake University, ( https://ror.org/05hfa4n20) Hangzhou, 310024 China
                [7 ]GuangDong Engineering Technology Research Center of Biological Targeting Diagnosis, Therapy and Rehabilitation, The Fifth Affiliated Hospital, Guangzhou Medical University, ( https://ror.org/00zat6v61) Guangzhou, China
                [8 ]Guangdong Engineering Research Center of Early Clinical Trials of Biotechnology Drugs, The Fifth Affiliated Hospital, Guangzhou Medical University, ( https://ror.org/00zat6v61) Guangzhou, China
                Author information
                http://orcid.org/0000-0001-7777-4045
                Article
                200
                10.1186/s13619-024-00200-2
                11399365
                39269631
                d4626d3e-d893-4a8f-81ba-869af5dfd6b9
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 7 May 2024
                : 1 September 2024
                Categories
                Research Article
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                © Chinese Society for Cell Biology 2024

                endogenous retroviruses,ervh48-1,human embryonic stem cells,induced pluripotent stem cells,urine cell integration-free reprogramming system

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