Article
Cell Biology
Qian Zhao, Kun Liu, Lin Zhang, Zheng Li, Liang Wang, Jiani Cao, Youqing Xu, Aihua Zheng, Quan Chen, Tongbiao Zhao
Summary: We discovered that BNIP3-dependent mitophagy protects genomic integrity in mouse ESCs by regulating ROS, ATP, and AMPK levels, affecting self-renewal, homologous recombination, and mutation load. Furthermore, BNIP3-dependent mitophagy also plays a role in reducing mutation accumulation during reprogramming.
CELL DEATH & DISEASE
(2022)
Article
Genetics & Heredity
Foad J. Rouhani, Xueqing Zou, Petr Danecek, Tauanne Dias Amarante, Gene Koh, Qianxin Wu, Yasin Memari, Richard Durbin, Inigo Martincorena, Andrew R. Bassett, Daniel Gaffney, Serena Nik-Zainal
Summary: The study explores human induced pluripotent stem cells derived from different tissues, finding UV-related damage and mutations in skin fibroblast-derived cells, while blood-derived cells show a high prevalence of acquired mutations.
Article
Multidisciplinary Sciences
Md Emon Cevallos, Ricardo Raul Cevallos, Ruowen Zhang, Kejin Hu
Summary: Research has found that the generation of induced pluripotent stem cells (iPSCs) is inefficient and stochastic. The reasons for these deficiencies are not yet clear. It has been shown that the reprogramming factors, OCT4, SOX2, and KLF4, induce significant reprogramming stress, including transcriptional turbulence, stress-response gene deregulation, cell cycle impairment, downregulation of mitotic genes, illegitimate reprogramming, and cytotoxicity. However, the dominant-negative peptides of BET proteins enhance iPSC reprogramming and alleviate these reprogramming stresses. These peptides target a similar set of genes as BET chemical inhibitors, suggesting a distinct approach to targeting BET proteins.
Article
Cell Biology
Raefa Abou Khouzam, Mohak Sharda, Shyama Prasad Rao, Stephanie Maame Kyerewah-Kersi, Nagwa Ahmed Zeinelabdin, Ayda Shah Mahmood, Husam Nawafleh, Munazza Samar Khan, Goutham Hassan Venkatesh, Salem Chouaib
Summary: Hypoxia has a significant impact on the microenvironment of solid tumors, promoting malignancy. In this study, we investigated the effects of long-term hypoxia exposure on transcriptional remodeling, tumor mutational burden (TMB), and genomic instability in cancer cells categorized based on their sensitivity or resistance to hypoxia. Our findings demonstrate that chronic hypoxia leads to metabolic reprogramming, modulation of proliferation, and increased genomic instability in tumor cells. These adaptive responses can be targeted to inhibit the growth and survival of cancer cells in chronically hypoxic tumor areas.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Editorial Material
Multidisciplinary Sciences
Roberto H. Herai, Ryan A. Szeto, Cleber A. Trujillo, Alysson R. Muotri
Summary: Researchers conducted an undisclosed in silico-only whole-exome sequencing analysis of the data, identifying genomic alterations in some clones previously undetected. However, most of these alterations could not be experimentally validated, with only one alteration remaining unconfirmed and having no impact on previous results or data interpretation.
Article
Biochemical Research Methods
Luca Denti, Parsoa Khorsand, Paola Bonizzoni, Fereydoun Hormozdiari, Rayan Chikhi
Summary: Structural variants (SVs) contribute to sequence variability in genomes and are significant in human genomics and precision medicine. However, due to the complexities of the human genome, SV discovery in individuals has been challenging. The introduction of low-error long-read sequencing technologies, such as PacBio HiFi, may provide a solution to these challenges.
Article
Biochemistry & Molecular Biology
David R. Porubsky, Mitchell T. Vollger, William N. Harvey, Allison Rozanski, Peter Ebert, Glenn Hickey, Patrick D. Hasenfeld, Ashley Sanders, Catherine O. Stober, Jan Korbel, Benedict E. Paten, Tobias Marschall, Evan Eichler
Summary: There has been significant progress in phased genome assembly by combining long-read data with parental information or linked-read data. However, the typical phased genome assembly still has over 140 gaps. A detailed analysis of 182 haploid assemblies reveals that the majority of assembly gaps cluster near large and identical repeats, resulting in disrupted protein-coding genes. Misorientations and alignment discontinuities are also identified, highlighting the need for algorithmic development and pangenome representation.
Article
Oncology
Henry de Traux de Wardin, Josephine K. Dermawan, Marie-Sophie Merlin, Leonard H. Wexler, Daniel Orbach, Fabio Vanoli, Gudrun Schleiermacher, Birgit Geoerger, Stelly Ballet, Delphine Guillemot, Eleonore Frouin, Stacy Cyrille, Olivier Delattre, Gaelle Pierron, Cristina R. Antonescu
Summary: This study explores the genomic spectrum of progression in rhabdomyosarcoma (RMS) and evaluates the best genomic approach using liquid biopsy. The results show that FP-RMS have a stable genome, while FN-RMS acquire more new alterations.
NPJ PRECISION ONCOLOGY
(2023)
Article
Biochemical Research Methods
Fei Qin, Xizhi Luo, Guoshuai Cai, Feifei Xiao
Summary: This study explores the correlation structure of whole-exome sequencing (WES) data and introduces a novel correlation-based CNV detection method, CORRseq, which outperforms existing methods in detecting medium and large CNVs. Modeling genomic correlation structure is advantageous for detecting relatively long CNVs.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Oncology
Cody Ashby, Eileen M. Boyle, Michael A. Bauer, Aneta Mikulasova, Christopher P. Wardell, Louis Williams, Ariel Siegel, Patrick Blaney, Marc Braunstein, David Kaminetsky, Jonathan Keats, Francesco Maura, Ola Landgren, Brian A. Walker, Faith E. Davies, Gareth J. Morgan
Summary: Deciphering genomic architecture helps identify disease drivers and understand myeloma initiation and progression mechanisms. This study demonstrates that structural variants occur nonrandomly in the genome, and their frequencies vary in different genetic contexts. The study also reveals the heterogeneity of transcriptional dysregulation caused by both canonical and novel structural variants, as well as the impact of complex rearrangements on clinical outcomes. Chromothripsis, in particular, has a significant negative effect on clinical outcome.
BLOOD CANCER JOURNAL
(2022)
Article
Cell & Tissue Engineering
Salma Alasmar, Jez Huang, Karishma Chopra, Ewa Baumann, Amy Aylsworth, Melissa Hewitt, Jagdeep K. Sandhu, Joseph S. Tauskela, Robert N. Ben, Anna Jezierski
Summary: This study investigated the role of ice recrystallization inhibitors (IRIs) as cryoprotectants for iPSCs and iPSC-derived neurons (iPSC-Ns). The results showed that IRIs, specifically 2FA, increased the post-thaw viability and recovery of iPSCs without affecting pluripotency. Although 2FA supplementation did not significantly improve iPSC-N cell post-thaw viability, 2FA cryopreserved iPSC-Ns exhibited better restoration of neuronal network activity and synaptic function compared to controls. This study highlights the importance of optimizing cryopreservation media formulations with IRIs to improve functional cryopreservation of iPSCs and post-mitotic iPSC-Ns.
Article
Biotechnology & Applied Microbiology
Jonathan R. Belyeu, Murad Chowdhury, Joseph Brown, Brent S. Pedersen, Michael J. Cormier, Aaron R. Quinlan, Ryan M. Layer
Summary: Samplot is a tool for creating images that display read depth and sequence alignments to adjudicate purported SVs, which can be rapidly reviewed to curate large SV call sets. It includes a machine learning package that decreases false positives without human review and is applicable to various biological problems.
Review
Biochemical Research Methods
Mian Umair Ahsan, Qian Liu, Jonathan Elliot Perdomo, Li Fang, Kai Wang
Summary: As long-read sequencing technologies become more popular, various methods have been developed for detecting and analyzing structural variants (SVs) from long reads. These methods are needed to adapt to the unique challenges and opportunities presented by long-read sequencing. This review summarizes more than 50 long-read-based methods for SV detection, genotyping, and visualization, and discusses how new telomere-to-telomere genome assemblies and pangenome efforts can enhance accuracy and drive the development of SV callers in the future.
Article
Oncology
Samuel Terkper Ahuno, Anna-Lisa Doebley, Thomas U. Ahearn, Joel Yarney, Nicholas Titiloye, Nancy Hamel, Ernest Adjei, Joe-Nat Clegg-Lamptey, Lawrence Edusei, Baffour Awuah, Xiaoyu Song, Verna Vanderpuye, Mustapha Abubakar, Maire Duggan, Daniel G. Stover, Kofi Nyarko, John M. S. Bartlett, Francis Aitpillah, Daniel Ansong, Kevin L. Gardner, Felix Andy Boateng, Anne M. Bowcock, Carlos Caldas, William D. Foulkes, Seth Wiafe, Beatrice Wiafe-Addai, Montserrat Garcia-Closas, Alexander Kwarteng, Gavin Ha, Jonine D. Figueroa, Paz Polak
Summary: ctDNA sequencing studies conducted on patients in sub-Saharan Africa revealed the detection of ctDNA in a majority of patients, despite not being selected for tumor grade and subtype. Additionally, breast cancer driver copy number alterations were observed in the majority of patients.
NPJ PRECISION ONCOLOGY
(2021)
Review
Cell Biology
Alexander Keller, Claudia Spits
Summary: Chromosomal abnormalities have a significant impact on the state of human pluripotent stem cells, especially in terms of their potential clinical applications. These abnormalities often exist in a mosaic state in culture, making them difficult to detect using conventional methods.
Article
Neurosciences
Min Ji Han, Won Ji Lee, Joonhyuk Choi, Yean Ju Hong, Sang Jun Uhm, Youngsok Choi, Jeong Tae Do
Summary: Adult stem cells, particularly neural stem cells (NSCs), show decreased differentiation potential with aging during long-term in vitro culture. However, introducing four reprogramming factors can inhibit NSC aging by decreasing the expression of inflammatory and ER stress-related genes. This rejuvenation method could enhance the potential of NSCs for neurological disease treatment.
JOURNAL OF COMPARATIVE NEUROLOGY
(2021)
Article
Environmental Sciences
Hyun-Jung Park, Won-Young Lee, Jeong Tae Do, Chankyu Park, Hyuk Song
Summary: BPA exposure inhibits fetal germ cell growth, disrupts Leydig cell development, and interferes with steroidogenesis in the fetal testis.
Article
Multidisciplinary Sciences
Torrin L. McDonald, Weichen Zhou, Christopher Castro, Camille Mumm, Jessica A. Switzenberg, Ryan E. Mills, Alan P. Boyle
Summary: Mobile element insertions (MEIs) are a source of repetitive genetic variation that can lead to genetic disorders. In this study, Cas9-targeted nanopore sequencing was used to efficiently saturate enrichment for known and non-reference MEIs.
NATURE COMMUNICATIONS
(2021)
Review
Cell Biology
Hyeonwoo La, Hyunjin Yoo, Young Bin Park, Nguyen Xuan Thang, Chanhyeok Park, Seonho Yoo, Hyeonji Lee, Youngsok Choi, Hyuk Song, Jeong Tae Do, Kwonho Hong
Summary: The lymphatic system is crucial for maintaining lipid and interstitial fluid homeostasis, as well as regulating immune cell development and functions. Recent studies have shown that epigenetic regulation plays a critical role in embryonic lymphatic endothelial cell (LEC) development and function. Understanding the epigenetic mechanisms involved in lymphatic development and function is important for managing lymphatic disorders.
Article
Cell & Tissue Engineering
Seong-Min Kim, Eun-Ji Kwon, Yun-Jeong Kim, Young-Hyun Go, Ji-Young Oh, Seokwoo Park, Jeong Tae Do, Keun-Tae Kim, Hyuk-Jin Cha
Summary: This study discovered the differential roles of Shp2 in naive and primed pluripotency and proposed the usage of iShp2 instead of iMek1 for the efficient maintenance and establishment of naive pluripotency.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Biotechnology & Applied Microbiology
Ji-Hye Seo, Si Won Jang, Young-Joo Jeon, So Young Eun, Yean Ju Hong, Jeong Tae Do, Jung-il Chae, Hyun Woo Choi
Summary: In this study, it was demonstrated that Licochalcone D (LCD) can improve the efficiency of induced pluripotent stem cell (iPSC) reprogramming and promote mesenchymal-to-epithelial transition (MET) during the early stages of reprogramming.
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Article
Cell Biology
Jae-Hoon Song, Joonhyuk Choi, Yean-Ju Hong, Hyeonwoo La, Tae-Kyung Hong, Kwonho Hong, Jeong-Tae Do
Summary: This study demonstrates the ability of extended pluripotent stem cells (EPSCs) to transfer their extended pluripotency directly to somatic cells through cell fusion. By fusing EPSCs with neural stem cells (NSCs), researchers observed fused cells with upregulated pluripotency markers and EPSC-specific gene expression, as well as contributions to extraembryonic and embryonic lineages both in vivo and in vitro.
Article
Engineering, Biomedical
Kyeong-Mo Koo, Young-Hyun Go, Seong-Min Kim, Chang-Dae Kim, Jeong Tae Do, Tae-Hyung Kim, Hyuk-Jin Cha
Summary: This study presents an electrochemical method for the label-free and non-destructive detection of naive embryonic stem cells (ESCs) derived from mouse ESCs, based on differences in cellular metabolism. By blocking glycolysis and oxidative phosphorylation, it was found that mitochondrial energy generation is the origin of the strong electrochemical signals of naive ESCs. The developed sensing platform can also sensitively identify mouse PSCs derived from MEFs among other cell types.
Article
Biochemistry & Molecular Biology
Seonho Yoo, Eun Joo Lee, Nguyen Xuan Thang, Hyeonwoo La, Hyeonji Lee, Chanhyeok Park, Dong Wook Han, Sang Jun Uhm, Hyuk Song, Jeong Tae Do, Youngsok Choi, Kwonho Hong
Summary: This study reveals the function of the ATP-dependent chromatin remodeler Ino80 in the cell cycle regulation of embryonic stem cells (ESCs). Loss of Ino80 leads to an extended cell cycle phase and cell apoptosis. Furthermore, the regulatory mechanism of Ino80 differs slightly in differentiating ESCs. This research demonstrates that Ino80 regulates the cell cycle of ESCs through transcriptional regulation, and its function may be universal to other cell types.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Sang Hoon Yoon, Ga Yeon Kim, Gyu Tae Choi, Jeong Tae Do
Summary: Turner syndrome is a genetic disorder characterized by incomplete dosage compensation of X-linked genes. It affects multiple organ systems and leads to various manifestations, including hypogonadotropic hypogonadism, short stature, cardiovascular abnormalities, liver and kidney disease, brain abnormalities, and skeletal problems. Understanding the phenotypic and disease manifestations of Turner syndrome in different organs is important for comprehensive management of patients with this condition.
Article
Biochemistry & Molecular Biology
Bong Jong Seo, Seung Bin Na, Joonhyuk Choi, Byeongyong Ahn, Omer Habib, Chankyu Park, Kwonho Hong, Jeong Tae Do
Summary: Deletion of the mitochondrial fission-related gene Dnml1 affects the differentiation ability of mouse embryonic stem cells (ESCs) and inhibits their pluripotency. This inhibition may be achieved through metabolic shift, G2/M phase arrest, and modulation of gene expression.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Seung Yeon Oh, Seung Bin Na, Yoo Kyung Kang, Jeong Tae Do
Summary: During early mammalian embryonic development, researchers have developed synthetic embryos or embryoids using stem cells as a powerful tool for studying embryogenesis and gastrulation. These synthetic embryos closely resemble early embryos in terms of morphology and gene expression, providing a faithful recapitulation of early embryonic development. This review discusses the progress and various approaches in studying in vitro embryogenesis and gastrulation in mice and humans using stem cells, as well as recent findings and breakthroughs in synthetic embryos and gastruloids. Despite ethical considerations, synthetic embryo models hold promise for understanding mammalian embryonic development and have implications for regenerative medicine and developmental research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell & Tissue Engineering
Yean Ju Hong, So Been Lee, Joonhyuk Choi, Sang Hoon Yoon, Jeong Tae Do
Summary: This study optimized a method to establish cerebral organoids from feeder-free cultured human pluripotent stem cells, focusing on the consistent production of neural progenitor cells and neurons. The researchers propose an optimal protocol applicable to both human embryonic stem cells and human induced pluripotent stem cells. Furthermore, the study established a routine method to generate early cerebral organoids comprising a cortical layer and a neural progenitor zone, and analyzed the morphology of brain organoids through 2D and 3D monitoring methods.
INTERNATIONAL JOURNAL OF STEM CELLS
(2022)
Article
Biotechnology & Applied Microbiology
Eui-Hwan Choi, Seobin Yoon, Young Eun Koh, Tae Kyung Hong, Jeong Tae Do, Bum-Kyu Lee, Yoonsoo Hahn, Keun P. Kim
Summary: The study reveals the functional roles of meiosis-specific cohesin complexes in mitotic chromosomes and their impact on chromosomal organization and the mitotic program in embryonic stem cells. The delicate balance between mitotic and meiotic cohesins is crucial for maintaining proper chromosome structure and function in ESCs.
Article
Biotechnology & Applied Microbiology
Yifan Wang, Taejeong Bae, Jeremy Thorpe, Maxwell A. Sherman, Attila G. Jones, Sean Cho, Kenneth Daily, Yanmei Dou, Javier Ganz, Alon Galor, Irene Lobon, Reenal Pattni, Chaggai Rosenbluh, Simone Tomasi, Livia Tomasini, Xiaoxu Yang, Bo Zhou, Schahram Akbarian, Laurel L. Ball, Sara Bizzotto, Sarah B. Emery, Ryan Doan, Liana Fasching, Yeongjun Jang, David Juan, Esther Lizano, Lovelace J. Luquette, John B. Moldovan, Rujuta Narurkar, Matthew T. Oetjens, Rachel E. Rodin, Shobana Sekar, Joo Heon Shin, Eduardo Soriano, Richard E. Straub, Weichen Zhou, Andrew Chess, Joseph G. Gleeson, Tomas Marques-Bonet, Peter J. Park, Mette A. Peters, Jonathan Pevsner, Christopher A. Walsh, Daniel R. Weinberger, Flora M. Vaccarino, John Moran, Alexander E. Urban, Jeffrey M. Kidd, Ryan E. Mills, Alexej Abyzov
Summary: This study successfully identified 43 somatic SNVs in non-cancerous tissues through a coordinated, multi-institutional research, and developed best practices for calling mosaic SNVs from whole-genome sequencing data that achieve 90% specificity and sensitivity. Furthermore, the results also demonstrate that analyzing multiple DNA samples from a single individual can reconstruct early developmental cell lineage trees.