{"title":"Rejuvenation to the Heart: Overcoming Age-Related Metabolic Barriers in Direct Cardiac Reprogramming.","authors":"Pedro P Cunha, Mariana Lopes","doi":"10.1089/cell.2025.0009","DOIUrl":"https://doi.org/10.1089/cell.2025.0009","url":null,"abstract":"<p><p>By dissecting metabolic and epigenetic features imposed by ageing in cardiomyocyte conversion from fetal and adult mouse fibroblasts, Santos et al. describe that metabolic modulation can enhance direct cardiac reprogramming.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076169","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}
Giulia Redi, Filomena Del Piano, Sara Cappellini, Martina Paladino, Anne den Breejen, Marcel H A M Fens, Massimiliano Caiazzo
{"title":"Delivery Systems in Neuronal Direct Cell Reprogramming.","authors":"Giulia Redi, Filomena Del Piano, Sara Cappellini, Martina Paladino, Anne den Breejen, Marcel H A M Fens, Massimiliano Caiazzo","doi":"10.1089/cell.2025.0008","DOIUrl":"https://doi.org/10.1089/cell.2025.0008","url":null,"abstract":"<p><p>Neuronal direct cell reprogramming approach allows direct conversion of somatic cells into neurons via forced expression of neuronal cell-lineage transcription factors (TFs). These so-called induced neuronal cells have significant potential as research tools and for therapeutic applications, such as in cell replacement therapy. However, the optimization of TF delivery strategies is crucial to reach clinical practice. In this review, we outlined the currently explored delivery technologies in neuronal direct cell reprogramming and their limitations and advantages. The first employed delivery strategies were mainly integrating viral systems, such as lentiviruses that exert consistently high transgene expression in most cell types. On the other hand, viral systems cause major safety concerns, including the risk for insertional mutagenesis and inflammation. More recently, several safer nonviral delivery systems have been investigated as well; however, these systems generally exert inferior reprogramming efficiency compared with viral systems. Emerging delivery technologies could provide new opportunities in the achievement of safe and effective delivery for neuronal direct cell reprogramming.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076162","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}
{"title":"Novel Insights into the Phospholipase C Delta 3 and Its Implications in Neoplastic Diseases.","authors":"Lindi Xu, Zhenli Li, Shuaishuai Zhu, Xingshun Qi, Wei Zhang, Yufu Tang","doi":"10.1089/cell.2025.0004","DOIUrl":"https://doi.org/10.1089/cell.2025.0004","url":null,"abstract":"<p><p>The phospholipase C (PLC) family plays a crucial role in the construction of biomembranes, cell growth, and signal transduction. PLC regulates multiple cellular processes by generating bioactive molecules such as inositol-1,4,5-triphosphate (IP<sub>3</sub>) and diacylglycerol (DAG). These products propagate and regulate cellular signaling via calcium (Ca<sup>2+</sup>) mobilization and activation of protein kinase C (PKC), other kinases, and ion channels. Recently, the function of PLC delta 3 (<i>PLCδ3</i>) has been arousing great interests in the basic research of neoplastic diseases. It is demonstrated to affect multiple parts of tumor progression and promote glycolysis reprogramming. However, currently there are no conclusive reports regarding the mechanism of <i>PLCδ3</i>-mediated tumor progression and its importance as a prognostic biomarker in specific neoplastic diseases. Therefore, the present article aimed to illustrate (1) the correlation between the function of phospholipases in PLC family and tumor progression; (2) the <i>PLCδ3</i>-mediated tumor progression, mainly focusing on the signal transduction and regulation; and (3) its potential mechanism and vital targets involved in multiple malignancies.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971201","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}
Alice E Lord, Leo J Dudley, Lynette Graver, Gabriella Ficz
{"title":"Old Habits Die Hard: DNA Methylation Patterns Persist in Experimental Transdifferentiation.","authors":"Alice E Lord, Leo J Dudley, Lynette Graver, Gabriella Ficz","doi":"10.1089/cell.2025.0020","DOIUrl":"https://doi.org/10.1089/cell.2025.0020","url":null,"abstract":"<p><p>The reprogramming of somatic cells into different lineages by transdifferentiation holds great promise for regenerative medicine and replacement therapies. However, a recent report by Radwan et al. (PNAS, 2024) finds that transdifferentiated cells fail to fully adopt the DNA methylation profiles of their new lineage. This has important implications regarding the viability of transdifferentiation as a strategy for cell replacement therapy.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954138","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}
{"title":"Menstrual Blood-Derived Mesenchymal Stem Cells Improve Endometrial Receptivity in a Mouse Model of Embryonic Implantation Dysfunction.","authors":"Chao Ma, Yue Yi, Changji Guan","doi":"10.1089/cell.2024.0071","DOIUrl":"https://doi.org/10.1089/cell.2024.0071","url":null,"abstract":"<p><p>The decrease of endometrial receptivity leads to repeated implantation failure (RIF) during in vitro fertilization and embryo transfer. To explore the therapeutic potential of menstrual blood-derived mesenchymal stem cells (MenSCs) in addressing RIF, we established a murine model of embryonic implantation dysfunction using mifepristone. Subsequently, we administered MenSCs to these mice via tail vein injection and assessed their impact on the implantation and pregnancy rates of the affected mice. Furthermore, we conducted immunohistochemical staining on uterine tissues from these mice to examine the expression of endometrial receptivity markers, specifically vascular endothelial growth factor (VEGF)-A, HAND2, and HOXA10 following MenSCs transplantation. In parallel, we conducted in vitro studies to elucidate the molecular mechanisms of cell therapy by measuring the expression levels of VEGF-A, HAND2, and HOXA10 in endometrial stromal cells using real-time PCR and western blotting. In our mifepristone-induced mouse models, we observed a reduction in both pregnancy rates and implantation sites; however, these parameters were significantly improved after MenSCs transplantation. Similarly, the expression levels of VEGF-A, HAND2, and HOXA10 in the uterine tissues of the mifepristone group were diminished, but these levels were restored following MenSCs therapy. In vitro, after mifepristone treating, the expression of VEGF-A, HAND2, and HOXA10 decreased in endometrial stromal cells, but their expression increased after MenSCs coculture supernatant. In conclusion, these results demonstrated that MenSCs transplantation could increase endometrial receptivity by upregulating VEGF-A, HAND2, and HOXA10 expression. This study suggests MenSCs as a novel stem cell candidate in the treatment of RIF.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976256","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}
Cellular reprogrammingPub Date : 2025-04-01Epub Date: 2025-03-20DOI: 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":"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":"75-85"},"PeriodicalIF":1.2,"publicationDate":"2025-04-01","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}
Cellular reprogrammingPub Date : 2025-04-01Epub Date: 2025-03-11DOI: 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":"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":"56-74"},"PeriodicalIF":1.2,"publicationDate":"2025-04-01","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}
Cellular reprogrammingPub Date : 2025-04-01Epub Date: 2025-03-24DOI: 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":"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":"86-93"},"PeriodicalIF":1.2,"publicationDate":"2025-04-01","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}
Cellular reprogrammingPub Date : 2025-04-01Epub Date: 2025-03-20DOI: 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":"10.1089/cell.2025.0014","url":null,"abstract":"","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":"47-52"},"PeriodicalIF":1.2,"publicationDate":"2025-04-01","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}
Cellular reprogrammingPub Date : 2025-04-01Epub Date: 2025-03-24DOI: 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":"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":"53-55"},"PeriodicalIF":1.2,"publicationDate":"2025-04-01","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}