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Locking the Fate: How PROX1 Represses Plasticity and Liver Cancer.
IF 1.2 4区 医学
Cellular reprogramming Pub Date : 2025-03-26 DOI: 10.1089/cell.2025.0013
Seung-Won Lee, Jungsun Kim
{"title":"Locking the Fate: How PROX1 Represses Plasticity and Liver Cancer.","authors":"Seung-Won Lee, Jungsun Kim","doi":"10.1089/cell.2025.0013","DOIUrl":"https://doi.org/10.1089/cell.2025.0013","url":null,"abstract":"<p><p>A Transcriptional Ridge in the Waddington Landscape. The Waddington landscape model, proposed in 1957, provides a powerful framework for understanding cell fate determination (Waddington, 1957). As development progresses, cells become restricted to distinct fates, separated by high \"ridges\" that prevent identity switching. A recent study in Nature Genetics uncovers such a ridge in hepatocyte lineage specification (Lim et al., 2025). Lim et al. report that prospero homeobox protein 1 (PROX1) acts as a hepatocyte-specific safeguard repressor, ensuring lineage stability by actively suppressing alternative cell fates and preventing cholangiocarcinoma development.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Editing the CYP19 Gene in Goat Embryos Using CRISPR/Cas9 and Somatic Cell Nuclear Transfer Techniques.
IF 1.2 4区 医学
Cellular reprogramming Pub Date : 2025-03-24 DOI: 10.1089/cell.2024.0109
Ahmad Pirali, Farnoosh Jafarpour, Mehdi Hajian, Seyed Hossein Hosseini Moghaddam, Reza Moradi, Nima Tanhaie-Vash, Mohsen Rahimi Andani, Tayebeh Izadi, Hanieh Shiralian-Esfahani, Zahra Safaeinejad, Wilfried Kues, Mohammad-Hossein Nasr-Esfahani, Shahin Eghbalsaied
{"title":"Editing the CYP19 Gene in Goat Embryos Using CRISPR/Cas9 and Somatic Cell Nuclear Transfer Techniques.","authors":"Ahmad Pirali, Farnoosh Jafarpour, Mehdi Hajian, Seyed Hossein Hosseini Moghaddam, Reza Moradi, Nima Tanhaie-Vash, Mohsen Rahimi Andani, Tayebeh Izadi, Hanieh Shiralian-Esfahani, Zahra Safaeinejad, Wilfried Kues, Mohammad-Hossein Nasr-Esfahani, Shahin Eghbalsaied","doi":"10.1089/cell.2024.0109","DOIUrl":"https://doi.org/10.1089/cell.2024.0109","url":null,"abstract":"<p><p>The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9) system is revolutionizing genome engineering and is expected to bring significant advancements in livestock traits, including the treatment of genetic diseases. This study focuses on CRISPR/Cas9-mediated modifications of the CYP19 gene, which encodes aromatase, an enzyme crucial for converting testosterone to estrogen and essential for steroid metabolism. Guide RNAs (gRNAs) were designed to target the CYP19 gene and cloned into the pX459 vector. The recombinant plasmid was then electrotransfected into fibroblast cells from a Lori-Bakhtiari buck, and these transfected cells were used for embryo production via somatic cell nuclear transfer (SCNT). The cloned embryos were evaluated for their progression through embryonic stages, showing no significant difference in blastocyst development between knock-out and unedited groups. The knockout efficiency was 78.4% in cells and 68.9% in goat blastocysts, demonstrating the successful depletion of CYP19. We successfully achieved a high rate of CYP19 gene-edited embryos through the combined application of cell electrotransfection and SCNT technologies, while maintaining the normal developmental rate of the embryos. These embryos can be used for transfer to generate knock-out goats, providing a foundation for further studies on CYP19's role in male fertility and production traits.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sox as a Functionally Conserved Link Between Unicellular Ancestors and Human Stem Cell Control.
IF 1.2 4区 医学
Cellular reprogramming Pub Date : 2025-03-24 DOI: 10.1089/cell.2025.0011
Emma U Hammarlund
{"title":"Sox as a Functionally Conserved Link Between Unicellular Ancestors and Human Stem Cell Control.","authors":"Emma U Hammarlund","doi":"10.1089/cell.2025.0011","DOIUrl":"https://doi.org/10.1089/cell.2025.0011","url":null,"abstract":"<p><p>Stem cells are key to human tissue maintenance. Because tissue maintenance allows us to live and reproduce, stem cell control is fundamental for animal life and evolution. A team of researchers set out to explore the origins of transcription factors at the core of the induction and the maintenance of stemnss. They focus on the conservation of the Sry-related box 2 (Sox2) and the octamer-binding transcriptor factor 4 (Oct4) in the Pit-Oct-Unc (POU) family. While these have been thought as animal-specific, the authors identified SOX and POU in pre-animal organisms. In particular, the SOX protein from a very simple unicellular organism was functionally conserved enough to reprogram somatic mouse cells to induce pluripotent stem cells. To ponder on the importance of their findings, we first need to step back a couple of hundred million years.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Proliferation Potential of Differentiated and Undifferentiated Spermatogonial Stem Cells on Diverse Feeder Layers.
IF 1.2 4区 医学
Cellular reprogramming Pub Date : 2025-03-20 DOI: 10.1089/cell.2024.0066
Kiana Sojoudi, Hossein Azizi, Maryam Solaimani
{"title":"The Proliferation Potential of Differentiated and Undifferentiated Spermatogonial Stem Cells on Diverse Feeder Layers.","authors":"Kiana Sojoudi, Hossein Azizi, Maryam Solaimani","doi":"10.1089/cell.2024.0066","DOIUrl":"https://doi.org/10.1089/cell.2024.0066","url":null,"abstract":"<p><p>Spermatogonial stem cells (SSCs) play an essential role in the transfer of genetic information through generations, making studying their cellular and molecular mechanisms critical. However, since SSCs are few in mice, directly studying them is limited, requiring specialized <i>in vitro</i> cultivation. Feeder layers such as mouse embryonic fibroblasts (MEFs), SNL, neonate, and adult mouse testicular stromal feeder cells (TSCs) support <i>in vitro</i> survival and growth. To understand the effectiveness of these feeder layers on SSC proliferation, we compared MEF, SNL, neonatal, and adult TSCs. Furthermore, we identified hub genes and potential pathways in spermatogenesis. Two populations of differentiated and undifferentiated SSCs were compared for mouse SSC colony formation and proliferation effectiveness. Additionally, Cytoscape and STRING databases were employed for protein-protein interaction networks and functional gene enrichment. The expression of three hub genes, including <i>Dazl</i>, <i>Zbtb16</i>, and <i>Stra8</i>, was analyzed using dynamic array chips (Fluidigm) followed by statistical analysis. Our results indicated that undifferentiated SSCs favored MEF feeders, while differentiated SSCs thrived on SNL and primary TSC feeders for long-term culture. Functional enrichment results demonstrated hub genes involvement in cell differentiation, meiosis, regulation of meiotic nuclear division, cell development, and spermatogenesis. Furthermore, mRNA expression levels of <i>Stra8</i>, <i>Zbtb16</i>, and <i>Dazl</i> genes show different patterns among feeder layers and SSC differentiation phases.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reprogramming Stars #21: RNA Regulatory Mechanisms That Instruct Cell Identity-An Interview with Dr. Bruno Di Stefano.
IF 1.2 4区 医学
Cellular reprogramming Pub Date : 2025-03-20 DOI: 10.1089/cell.2025.0014
Bruno Di Stefano, Mariana Lopes, Carlos-Filipe Pereira
{"title":"Reprogramming Stars #21: RNA Regulatory Mechanisms That Instruct Cell Identity-An Interview with Dr. Bruno Di Stefano.","authors":"Bruno Di Stefano, Mariana Lopes, Carlos-Filipe Pereira","doi":"10.1089/cell.2025.0014","DOIUrl":"https://doi.org/10.1089/cell.2025.0014","url":null,"abstract":"","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nearly a Century of Nuclear Transfer Research: Milestones, Applications, and Challenges.
IF 1.2 4区 医学
Cellular reprogramming Pub Date : 2025-03-11 DOI: 10.1089/cell.2024.0089
Yiren Qin
{"title":"Nearly a Century of Nuclear Transfer Research: Milestones, Applications, and Challenges.","authors":"Yiren Qin","doi":"10.1089/cell.2024.0089","DOIUrl":"https://doi.org/10.1089/cell.2024.0089","url":null,"abstract":"<p><p>From the first cloning of animals-salamanders-to the cloning of primates-monkeys-nuclear transfer research has spanned an extensive 96-year history. Over the course of nearly a century, it has addressed fundamental scientific questions and found applications across a wide range of practical fields. This review provides a comprehensive overview of the key milestones in its development, its practical applications, and the challenges it continues to face.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reprogramming Stars #20: Attenuating Cancer Cell Memory and Discovering Cancer Biomarkers with Cellular Reprogramming-An Interview with Dr. Jungsun Kim.
IF 1.2 4区 医学
Cellular reprogramming Pub Date : 2025-02-01 Epub Date: 2025-01-29 DOI: 10.1089/cell.2025.0007
Jungsun Kim, Mariana Lopes, Carlos-Filipe Pereira
{"title":"Reprogramming Stars #20: Attenuating Cancer Cell Memory and Discovering Cancer Biomarkers with Cellular Reprogramming-An Interview with Dr. Jungsun Kim.","authors":"Jungsun Kim, Mariana Lopes, Carlos-Filipe Pereira","doi":"10.1089/cell.2025.0007","DOIUrl":"10.1089/cell.2025.0007","url":null,"abstract":"","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":"1-6"},"PeriodicalIF":1.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bidirectional Prime Editing: Combining Precision with Versatility for Genome Editing. 双向启动编辑：基因组编辑的精确性与多功能性相结合。
IF 1.2 4区 医学
Cellular reprogramming Pub Date : 2025-02-01 Epub Date: 2024-12-17 DOI: 10.1089/cell.2024.0075
Mahmood S Choudhery, Taqdees Arif, Ruhma Mahmood
{"title":"Bidirectional Prime Editing: Combining Precision with Versatility for Genome Editing.","authors":"Mahmood S Choudhery, Taqdees Arif, Ruhma Mahmood","doi":"10.1089/cell.2024.0075","DOIUrl":"10.1089/cell.2024.0075","url":null,"abstract":"<p><p>Genome editing techniques have potential to revolutionize the field of life sciences. Several limitations associated with traditional gene editing techniques have been resolved with the development of prime editors that precisely edit the DNA without double-strand breaks (DSBs). To further improve the efficiency, several modified versions of prime editing (PE) system have been introduced. Bi-directional PE (Bi-PE), for example, uses two PE guide RNAs enabling broad and improved editing efficiency. It has the potential to alter, delete, integrate, and replace larger genome sequences and edit multiple bases at the same time. This review aims to discuss the typical gene editing methods that offer DSB-mediated repair mechanisms, followed by the latest advances in genome editing technologies with non-DSB-mediated repair. The review specifically focuses on Bi-PE being an efficient tool to edit the human genome. In addition, the review discusses the applications, limitations, and future perspectives of Bi-PE for gene editing.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":"10-23"},"PeriodicalIF":1.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular Mechanisms and Strategies for Inducing Neuronal Differentiation in Glioblastoma Cells.
IF 1.2 4区 医学
Cellular reprogramming Pub Date : 2025-02-01 Epub Date: 2025-01-30 DOI: 10.1089/cell.2024.0087
Zhao-Qi Tang, Yan-Rong Ye, Yun Shen
{"title":"Molecular Mechanisms and Strategies for Inducing Neuronal Differentiation in Glioblastoma Cells.","authors":"Zhao-Qi Tang, Yan-Rong Ye, Yun Shen","doi":"10.1089/cell.2024.0087","DOIUrl":"10.1089/cell.2024.0087","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is a highly invasive brain tumor, and traditional treatments combining surgery with radiochemotherapy have limited effects, with tumor recurrence being almost inevitable. Given the lack of proliferative capacity in neurons, inducing terminal differentiation of GBM cells or glioma stem cells (GSCs) into neuron-like cells has emerged as a promising strategy. This approach aims to suppress their proliferation and self-renewal capabilities through differentiation. This review summarizes the methods involved in recent research on the neuronal differentiation of GBM cells or GSCs, including the regulation of transcription factors, signaling pathways, miRNA, and the use of small molecule drugs, among various strategies. It also outlines the interconnections between the mechanisms studied, hoping to provide ideas for exploring new therapeutic avenues for GBM and the development of differentiation-inducing drugs for GBM.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":"24-32"},"PeriodicalIF":1.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protective Effect and Molecular Mechanism of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Diabetic Foot Ulcers. 间充质干细胞来源的细胞外囊泡对糖尿病足溃疡的保护作用及其分子机制。
IF 1.2 4区 医学
Cellular reprogramming Pub Date : 2025-02-01 Epub Date: 2024-11-29 DOI: 10.1089/cell.2024.0062
Jian Zhao, Yan Gu, Peng Hou
{"title":"Protective Effect and Molecular Mechanism of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Diabetic Foot Ulcers.","authors":"Jian Zhao, Yan Gu, Peng Hou","doi":"10.1089/cell.2024.0062","DOIUrl":"10.1089/cell.2024.0062","url":null,"abstract":"<p><p>This study explores the protective mechanism of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in diabetic foot ulcer (DFU). Human umbilical cord MSCs (HucMSCs) were identified via osteogenesis and adipogenic differentiation, as well as flow cytometry. EVs were isolated from HucMSCs and characterized using transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. Fluorescence microscopy revealed the uptake of PKH67-labeled EVs and Cy3-labeled microRNA-21-5p (miR-21-5p) by human skin fibroblasts (HSFs). EVs were cocultured with HSFs, and cell proliferation and migration were assessed using Cell Counting Kit-8, colony formation, scratch, and Transwell assays. miR-21-5p overexpression in EVs was evaluated for its role in promoting HSF functions. The expression levels of miR-21-5p, Krüppel-like factor 6 (KLF6), α-smooth muscle actin, and collagen type I alpha 1 chain were analyzed via quantitative real-time PCR and Western blotting. The interaction between miR-21-5p and KLF6 was confirmed through a dual-luciferase reporter gene assay. HucMSC-derived EVs enhanced the proliferation and migration of HSFs under high glucose by delivering miR-21-5p, which targeted and inhibited KLF6. Overexpression of KLF6 counteracted the pro-proliferative and migratory effects of EVs carrying miR-21-5p. Overall, these findings suggest that HucMSC-EVs promote HSF proliferation and migration by downregulating KLF6 via miR-21-5p delivery, offering a potential therapeutic strategy for DFU.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":"33-44"},"PeriodicalIF":1.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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