Article
Cell & Tissue Engineering
Xiaotong Wang, Mengyuan Qu, Zili Li, Yuting Long, Kai Hong, Honggang Li
Summary: The study developed a protocol to induce spermatogonial stem cell-like cells (SSCLCs) from human pluripotent stem cells, revealing that a combination of low concentrations of VPA and VC was most effective in inducing SSCLCs expressing spermatogonial genes. RNA-seq analysis showed upregulated genes in the Wnt signaling pathway during SSCLC induction. Additionally, hiPSC lines from non-obstructive azoospermia (NOA) patients exhibited decreased SSCLC induction efficiency and reduced expression of genes in the Wnt signaling pathway. The study suggests that the inactivation of the Wnt signaling pathway may be associated with SSC depletion in azoospermia testes.
STEM CELL RESEARCH & THERAPY
(2021)
Review
Endocrinology & Metabolism
Ila Tewari Jasra, Nerea Cuesta-Gomez, Kevin Verhoeff, Braulio A. Marfil-Garza, Nidheesh Dadheech, A. M. James Shapiro
Summary: This review summarizes the roles and mechanisms of mitochondria in somatic cell reprogramming to iPSCs and the metabolic shift associated with directed differentiation into pancreatic beta-like cells.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Genetics & Heredity
Riccardo M. Betto, Linda Diamante, Valentina Perrera, Matteo Audano, Stefania Rapelli, Andrea Lauria, Danny Incarnato, Mattia Arboit, Silvia Pedretti, Giovanni Rigoni, Vincent Guerineau, David Touboul, Giuliano Giuseppe Stirparo, Tim Lohoff, Thorsten Boroviak, Paolo Grumati, Maria E. Soriano, Jennifer Nichols, Nico Mitro, Salvatore Oliviero, Graziano Martello
Summary: This study reveals that LIF-Stat3 signaling induces genomic hypomethylation through metabolic reconfiguration, impacting the developmental plasticity of cells. Genome methylation is dynamically controlled via regulation of alpha-ketoglutarate availability or Stat3 activation. The transcription factor Otx2 is linked to DNA methylation through alpha-ketoglutarate, affecting the epigenome.
Article
Chemistry, Multidisciplinary
Deogil Kim, Byung-Hyun Cha, Jinsung Ahn, Yoshie Arai, Bogyu Choi, Soo-Hong Lee
Summary: Understanding the biophysical relationships between stem cells and applied biomaterials is crucial in controlling stem cell functions. This study highlights the significant role of 3D microenvironment, particularly methacrylated hyaluronic acid (HA) hydrogel, in improving cellular reprogramming into iPSCs. The incorporation of cues from the 3D microenvironment accelerates the reprogramming process, offering potential advantages for translational applications.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Multidisciplinary Sciences
Jingyang Guan, Guan Wang, Jinlin Wang, Zhengyuan Zhang, Yao Fu, Lin Cheng, Gaofan Meng, Yulin Lyu, Jialiang Zhu, Yanqin Li, Yanglu Wang, Shijia Liuyang, Bei Liu, Zirun Yang, Huanjing He, Xinxing Zhong, Qijing Chen, Xu Zhang, Shicheng Sun, Weifeng Lai, Yan Shi, Lulu Liu, Lipeng Wang, Cheng Li, Shichun Lu, Hongkui Deng
Summary: This study demonstrates the chemical reprogramming of human somatic cells to human chemically induced pluripotent stem cells, which exhibit key features of embryonic stem cells. The induction of an intermediate plastic state and inhibition of the JNK pathway are crucial for successful chemical reprogramming.
Article
Cell Biology
Yuhan Chen, Jiansen Lu, Yanwen Xu, Yaping Huang, Dazhuang Wang, Peiling Liang, Shaofang Ren, Xuesong Hu, Yewen Qin, Wei Ke, Ralf Jauch, Andrew Paul Hutchins, Mei Wang, Fuchou Tang, Xiao-Yang Zhao
Summary: Although chemical induced pluripotent stem cells (CiPSCs) have been generated from somatic cells using pure chemicals, their authenticity as pluripotent stem cells has never been confirmed through tetraploid complementation assay. However, in this study, researchers successfully reprogrammed spermatogonial stem cells (SSCs) using a five-chemical combination, resulting in the production of chemically induced germline-derived PSCs (5C-gPSCs) with authentic pluripotency. The reprogramming process involved a unique regulatory network and exhibited expression signatures and DNA methylation dynamics similar to in vivo germ cell development. The findings provide insights into cell-fate decision and epigenetic-related disorders in regenerative medicine.
Article
Cell Biology
Sitong Liu, Rui Wei, Hongyang Liu, Ruiqi Liu, Pengxiao Li, Xiaoyu Zhang, Wei Wei, Xiaodong Zhao, Xiaomeng Li, Yang Yang, Xueqi Fu, Kang Zou
Summary: This study demonstrates the connection between p53 and pluripotency-associated factors in the transformation of SSCs, with SMAD3 identified as a key factor. However, an unknown event is required to activate SMAD3, serving as a prerequisite for SSCs reprogramming in long-term culture.
CELL PROLIFERATION
(2022)
Article
Oncology
A. Pham, C. Selenou, E. Giabicani, V. Fontaine, S. Marteau, F. Brioude, L. David, D. Mitanchez, M. L. Sobrier, I. Netchine
Summary: This study extensively analyzed the methylation levels of imprinted control regions (ICRs) in iPSCs and found abnormal hypermethylation at certain ICRs, resulting in loss of parental imprinting (LOI) and biallelic expression of imprinted genes. They also discovered that the epiPS (TM) culture medium and culturing iPSCs under hypoxic conditions prevented hypermethylation at ICRs while preserving the properties of iPSCs. This suggests that human iPSCs are a promising cellular model to study the physiopathology of imprinting disorders (IDs) and test therapeutic strategies.
CLINICAL EPIGENETICS
(2022)
Review
Immunology
Niclas Flosdorf, Martin Zenke
Summary: Novel methods of generating dendritic cells (DC) through reprogramming somatic cells have opened up exciting avenues for research and clinical applications. Induced pluripotent stem cells (iPS cells) and direct reprogramming of cells can both be used to generate DC.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Cell & Tissue Engineering
Yukyeong Lee, Seung-Won Lee, Dahee Jeong, Hye Jeong Lee, Na Young Choi, Jin Seok Bang, Seokbeom Ham, Kinarm Ko
Summary: The study found that the use of epigenetic modulators can enhance the self-reprogramming efficiency of SSCs, which is significant for inducing pluripotency in somatic cells.
INTERNATIONAL JOURNAL OF STEM CELLS
(2022)
Article
Biology
Joao C. Sabino, Madalena R. de Almeida, Patricia L. Abreu, Ana M. Ferreira, Paulo Caldas, Marco M. Domingues, Nuno C. Santos, Claus M. Azzalin, Ana Rita Grosso, Sergio Fernandes de Almeida
Summary: The activity of TET enzymes promotes the formation of R-loops, revealing new mechanisms of gene expression regulation.
Article
Cell & Tissue Engineering
Kazuto Kimura, Masaya Tsukamoto, Miyuu Tanaka, Mitsuru Kuwamura, Manami Ohtaka, Ken Nishimura, Mahito Nakanishi, Kikuya Sugiura, Shingo Hatoya
Summary: This study developed an efficient strategy to generate ciPSCs from canine PBMCs by adding small-molecule compounds in the medium. The generated ciPSCs demonstrated pluripotency characteristics, maintained a normal karyotype, and could differentiate into cells from three germ layers. This method provides a potential tool for disease modeling and regenerative medicine in veterinary field.
STEM CELLS AND DEVELOPMENT
(2021)
Article
Cell Biology
Olga A. Krasnova, Karina A. Kulakova, Julia V. Sopova, Evgenyi Y. Smirnov, Sergey A. Silonov, Ekaterina V. Lomert, Olga A. Bystrova, Marina G. Martynova, Irina E. Neganova
Summary: G-protein-coupled receptors (GPCRs) are the largest family of cell surface receptors and play important roles in diverse developmental processes. However, their role in pluripotency maintenance and acquisition during reprogramming towards hiPSCs has been overlooked. Through RNA interference screening, adhesion GPCR GPR123 was identified as a potential reprogramming effector. Suppression of GPR123 leads to loss of pluripotency and differentiation in hPSCs, suggesting its essential role in maintaining and acquiring pluripotency.
Article
Cell & Tissue Engineering
Sandhya Sriram, Nam-Young Kang, Subha Subramanian, Tannistha Nandi, Samydurai Sudhagar, Qiaorui Xing, Gerine Jin-Ling Tong, Allen Kuan-Liang Chen, Thekkeparambil Chandrabose Srijaya, Patrick Tan, Yuin-Han Loh, Young-Tae Chang, Shigeki Sugii
Summary: In this study, a novel BODIPY-derived fluorescent probe, BDL-E5, was identified to detect live human iPS cells at the early reprogramming stage, enabling early identification of reprogramming cells and improving the efficiency of iPS cell generation. RNA sequencing analysis revealed early reprogramming gene expression patterns, particularly involving CREB1, which was found to significantly impact reprogramming efficiency when overexpressed or knocked down. Overall, BDL-E5 provides a valuable tool for studying the early reprogramming pathway and enhancing the production of human iPS cells for clinical applications.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Medicine, General & Internal
Chao-Yu Liu, Ming-Cheng Lee, Heng-Fu Lin, Yi-Ying Lin, Wei-Yi Lai, Yueh Chien, Teh-Ia Huo, Wen-Liang Lo, Yuan-Tzu Lan, Yi-Wei Chen, Pin- Huang, Yong-Yang Liu, Meng-Yin Yang
Summary: This study utilized nanodiamond as a gene delivery vehicle to carry microRNA (miR-181a) into induced pluripotent stem cells (iPS) to promote cardiomyocyte-lineage differentiation. The miR-181a targeted Hox-A11, leading to elevated MyoD expression and enhanced cardiomyocyte differentiation.
JOURNAL OF THE CHINESE MEDICAL ASSOCIATION
(2021)
Article
Developmental Biology
Priscila Ramos-Ibeas, Leopoldo Gonzalez-Brusi, Maria Torres Used, Maria Jesus Cocero, Pilar Marigorta, Ramiro Alberio, Pablo Bermejo-Alvarez
Summary: Developmental failures occurring after blastocyst hatching from the zona pellucida are a major cause of pregnancy losses in both humans and farm ungulates. Current culture systems cannot support ungulate embryo development beyond hatching, limiting our understanding of key processes for embryo survival. This study reports a culture system that recapitulates most developmental landmarks of gastrulating ovine embryos, providing a valuable platform for studying pregnancy failures during the second week of gestation.
Article
Oncology
Cristian Garcia-Ruiz, Cristina Martinez-Valiente, Lourdes Cordon, Alessandro Liquori, Raul Fernandez-Gonzalez, Eva Pericuesta, Juan Sandoval, Jose Cervera, Alfonso Gutierrez-Adan, Alejandra Sanjuan-Pla
Summary: RNA splicing and epigenetic gene mutations are frequent genetic lesions in MDS patients. Mutations in ZRSR2 and TET2 are commonly found together and can initiate MDS in mice. Understanding this interaction will be important for finding new therapeutic targets.
Article
Agriculture, Dairy & Animal Science
Claudia Lima Verde Leal, Karina Canon-Beltran, Yulia N. Cajas, Meriem Hamdi, Aracelli Yaryes, Maria Gemma Millan de la Blanca, Paula Beltran-Brena, Rosane Mazzarella, Juliano Coelho da Silveira, Alfonso Gutierrez-Adan, Encina M. Gonzalez, Dimitrios Rizos
Summary: This study aimed to evaluate the effect of extracellular vesicles (EVs) isolated from oviductal fluid (OF) and uterine fluid (UF) on the development and quality of bovine embryos in vitro. The results showed that the use of EVs improved blastocyst quality, including survival rate after vitrification/warming, total cell number, lipid content, and the expression of lipid metabolism-related genes. Additionally, the miRNA contents in EVs may contribute to these observed effects.
JOURNAL OF ANIMAL SCIENCE AND BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Itishree Jali, Venkata Krishna Vanamamalai, Priyanka Garg, Paula Navarrete, Alfonso Gutierrez-Adan, Shailesh Sharma
Summary: This study analyzed RNA-seq data from bovine genital ridges of early embryonic stages and identified a large number of lncRNA transcripts. The study also investigated the co-expression between lncRNAs and the XIST gene, revealing a potential important role of differentially expressed lncRNAs during embryo development in bovine.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Reproductive Biology
Beatriz Galiano-Cogolludo, Pilar Marigorta, Victor Yus Giron, Pablo Bermejo-Alvarez, Priscila Ramos-Ibeas
Summary: The development failures occurring between blastocyst hatching and implantation in farm ungulates contribute significantly to pregnancy losses. The study focused on the post-hatching developmental period of the ovine embryo and investigated the impact of TGF13 inhibition on hypoblast and epiblast development. The findings revealed the negative effect of TGF13 inhibition, which could be partially reversed by ROCK inhibitor Y-27632, providing insights into the molecular networks regulating embryo development and the causes of early pregnancy losses in farm ungulates.
Article
Agriculture, Dairy & Animal Science
Sara Ruiz-Diaz, Rosane Mazzarella, Paula Navarrete-Lopez, Raul Fernandez-Gonzalez, Celia de Frutos, Maria Maroto, Claudia Cucala, Paula Beltran-Brena, Marta Lombo, Dimitrios Rizos, Alfonso Gutierrez-Adan
Summary: This study aimed to analyze if bull spermatozoa could be selected by thermotaxis and to assess their quality in terms of SDF as well as determine the presence of a specific sperm subpopulation based on sperm morphometry and assess their fertilizing capacity by ICSI. The results showed that thermotactic sperm selection led to higher DNA integrity, small and elongated head size parameters, and a different sperm subpopulation structure.
JOURNAL OF ANIMAL SCIENCE AND BIOTECHNOLOGY
(2023)
Article
Developmental Biology
Paula Navarrete-Lopez, Marta Lombo, Maria Maroto, Eva Pericuesta, Raul Fernandez-Gonzalez, Priscila Ramos-Ibeas, Maria Teresa Parra, Alberto Viera, Jose Angel Suja, Alfonso Gutierrez-Adan
Summary: In this study, the role of the testis-specific IQ motif-containing H gene (Iqch) in the regulation of alternative splicing during spermatogenesis was characterized using a mutant mouse model. The findings suggested that Iqch is essential for the specific expression of RNA isoforms and interacts with other proteins to regulate alternative splicing events. The study also revealed the downregulation of testis-specific lncRNAs and protein-coding genes, as well as alterations in alternative splicing patterns, resulting in male infertility.
Article
Reproductive Biology
Karina Canon-Beltran, Yulia N. Cajas, Encina Gonzalez, Raul Fernandez-Gonzalez, Natacha Fierro, Pedro L. Lorenzo, Maria Arias-Alvarez, Rosa M. Garcia-Garcia, Alfonso Gutierrez-Adan, Dimitrios Rizos
Summary: Guinea pig in vitro fertilization (IVF) is underdeveloped due to limited oocyte accessibility and lack of efficient sperm capacitation methods. In this study, we evaluated different capacitation protocols and validated them through sperm analysis and heterologous IVF with bovine oocytes. Protocols C and D showed higher viability, motility, and acrosome reaction of spermatozoa compared to protocols A and B. Further analysis revealed that protocol D achieved higher pro-nuclear formation and cleavage rate in heterologous IVF, suggesting its suitability for guinea pig IVF.
Article
Immunology
Miguel Rodriguez-Pulido, Eva Calvo-Pinilla, Miryam Polo, Juan-Carlos Saiz, Raul Fernandez-Gonzalez, Eva Pericuesta, Alfonso Gutierrez-Adan, Francisco Sobrino, Miguel A. Martin-Acebes, Margarita Saiz
Summary: We evaluated the antiviral activity of synthetic RNAs mimicking specific domains in the non-coding regions of the foot-and-mouth disease virus (FMDV) genome (ncRNAs), which have shown broad-spectrum antiviral activity. The ncRNAs exhibited potent antiviral activity against SARS-CoV-2 in human intestinal and lung epithelium cells. In vivo efficacy studies using K18-hACE2 mice showed that administration of naked ncRNA before SARS-CoV-2 infection significantly reduced viral load and pro-inflammatory cytokines in the lungs. Furthermore, the ncRNAs were highly effective against other coronaviruses in human and swine cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Paula Navarrete-Lopez, Maria Maroto, Eva Pericuesta, Raul Fernandez-Gonzalez, Marta Lombo, Priscila Ramos-Ibeas, Alfonso Gutierrez-Adan
Summary: Kpna2 plays a crucial role in spermatogenesis. Knockout male mice lacking Kpna2 displayed reduced body size, decreased sperm motility, increased sperm abnormalities, dysregulated testis gene expression, and ultimately infertility. The impaired mRNA expression mainly affected gene clusters expressed in spermatids and spermatocytes, including genes involved in cell adhesion and extracellular matrix organization.
Article
Food Science & Technology
Ana Ruiz de la Bastida, Susana Langa, Angela Peiroten, Raul Fernandez-Gonzalez, Abel Sanchez-Jimenez, Maria Maroto, Jose Antonio Curiel, Eva Guillamon, Juan Luis Arques, Alfonso Gutierrez-Adan, Jose Maria Landetea
Summary: This study evaluated the health effects of two soy beverages, non-fermented and fermented, on aged female mice as a model of menopause and premenopause. The fermented soy beverage showed better outcomes in lipid profile and fertility, possibly due to the production of more bioavailable and bioactive compounds through the fermentation process.
FOOD RESEARCH INTERNATIONAL
(2023)
Article
Reproductive Biology
P. Ramos-Ibeas, A. Perez-Gomez, L. Gonzalez-Brusi, A. C. Quiroga, P. Bermejo-Alvares
Summary: Ungulate embryos undergo critical cell differentiation and proliferation events around and after blastocyst hatching. Failures in these processes lead to early pregnancy losses. Conventional embryo culture media are unable to support embryo development beyond hatching, while N2B27 medium supports early post-hatching development. The study found that culturing bovine embryos in N2B27 from day 7 onwards improves subsequent post-hatching development, providing a useful in vitro system for studying cell differentiation mechanisms and early pregnancy failures.
Meeting Abstract
Agriculture, Dairy & Animal Science
M. Maroto, P. Navarrete-Lopez, E. Pericuesta, S. Huin, M. Fons-Contreras, R. Fernandez-Gonzalez, A. Gutierrez-Adan
REPRODUCTION IN DOMESTIC ANIMALS
(2022)
Meeting Abstract
Agriculture, Dairy & Animal Science
P. Navarrete-Lopez, M. Lombo, M. Maroto, R. Fernandez-Gonzalez, E. Pericuesta, P. Ramos-Ibeas, A. Gutierrez-Adan
REPRODUCTION IN DOMESTIC ANIMALS
(2022)
