Article
Biochemistry & Molecular Biology
Sun Woo Lim, Xianying Fang, Sheng Cui, Hanbi Lee, Yoo Jin Shin, Eun Jeong Ko, Kang In Lee, Jae Young Lee, Byung Ha Chung, Chul Woo Yang
Summary: The aim of this study was to use human-induced pluripotent stem cell (hiPSC)-derived kidney organoids to model Gitelman's disease (GIT) and investigate the potential of CRISPR/Cas9 gene correction to rescue the disease phenotype. The researchers generated a hiPSC line (CMC-GIT-001) from GIT patients with SLC12A3 gene mutation and used the CRISPR-Cas9 system to correct the mutations, generating a corrected hiPSC line (CMC-GIT-001(corr)). The study demonstrated that kidney organoids derived from CMC-GIT-001(corr) showed improved maturity and increased sodium chloride cotransporter (NCCT) expression compared to CMC-GIT-001, indicating successful rescue of the GIT phenotype using gene correction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell & Tissue Engineering
Yuanxiu Song, Tianwei Guo, Youxu Jiang, Min Zhu, Hongyue Wang, Wenjing Lu, Mengqi Jiang, Man Qi, Feng Lan, Ming Cui
Summary: In this study, a human cardiomyocyte (CM) model with KCNQ1 deficiency and mutation was established by knocking out the KCNQ1 gene in human embryonic stem cells (hESCs) using the CRISPR/cas9 system. By performing high-throughput microelectrode array (MEA) analysis and drug intervention, the electrophysiological characteristics of KCNQ1-deficient and KCNQ1-mutant CMs were determined.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Biochemical Research Methods
Delilah Hendriks, Benedetta Artegiani, Huili Hu, Susana Chuva de Sousa Lopes, Hans Clevers
Summary: This protocol provides detailed culture conditions for long-term expansion of human fetal hepatocytes as organoids and introduces methods for gene editing using CRISPR-Cas9. These approaches are valuable for disease modeling, gene function studies, as well as research on cellular differentiation and cell division processes.
Article
Virology
Anna Z. Mykytyn, Tim I. Breugem, Maarten H. Geurts, Joep Beumer, Debby Schipper, Romy van Acker, Petra B. van den Doel, Martin E. van Royen, Jingshu Zhang, Hans Clevers, Bart L. Haagmans, Mart M. Lamers
Summary: Coronavirus entry relies on host proteases that activate the viral fusion protein, spike. These proteases determine the viral entry route, tropism, host range, and can be attractive drug targets. Our study found that the protease usage of SARS-CoV-2 has not changed in human airway and intestinal organoid models, contrary to earlier studies using cell lines. This suggests that host TTSP inhibition is still a viable prophylactic or therapeutic antiviral strategy against current SARS-CoV-2 variants and highlights the importance of relevant human in vitro cell models.
JOURNAL OF VIROLOGY
(2023)
Article
Medicine, Research & Experimental
Victor Tiroille, Adrien Krug, Emma Bokobza, Michel Kahi, Mattijs Bulcaen, Marjolein M. Ensinck, Maarten H. Geurts, Delilah Hendriks, Francois Vermeulen, Frederic Larbret, Alejandra Gutierrez-Guerrero, Yu Chen, Indra Van Zundert, Susana Rocha, Anne C. Rios, Louise Medaer, Rik Gijsbers, Philippe E. Mangeot, Hans Clevers, Marianne S. Carlon, Frederic Bost, Els Verhoeyan
Summary: The use of CRISPR/Cas9 gene editing system in synthetic organs called 'organoids' is still inefficient. This study introduces the 'nanoblade' technology, which achieves high-level gene editing with little toxicity in murine and human tissue-derived organoids. The nanoblades allow rapid and simplified genome editing with stable gene knock-out in just four weeks.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Cell Biology
Yuting Fu, Fangyuan Liu, Shuo Cao, Jia Zhang, Huizhi Wang, Baojiang Wu, Yongli Song, Shuguang Duo, Xihe Li, Siqin Bao
Summary: This study reveals that Bdh2 deficiency has no impact on pluripotency and self-renewal of ESCs, but promotes endoderm differentiation and is essential for maintaining DNA methylation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Virology
Myung-Ju Lee, Jisu Lee, Su-Kyung Kang, Dagmar Wirth, Seung-Min Yoo, Changhoon Park, Myung-Shin Lee
Summary: This study investigated the role of cytokines in KSHV-infected endothelial cells by manipulating target genes using the CRISPR/Cas9 system. CXCL1 was found to be highly upregulated following KSHV infection and its knockout resulted in increased cell death and suppressed phosphorylation of STAT3. These findings suggest that CXCL1 production is essential for the survival of KSHV-infected endothelial cells.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Emanuel Goncalves, Mark Thomas, Fiona M. Behan, Gabriele Picco, Clare Pacini, Felicity Allen, Alessandro Vinceti, Mamta Sharma, David A. Jackson, Stacey Price, Charlotte M. Beaver, Oliver Dovey, David Parry-Smith, Francesco Iorio, Leopold Parts, Kosuke Yusa, Mathew J. Garnett
Summary: MinLibCas9 is an optimized human genome-wide CRISPR-Cas9 library that reduces the size by over 42% compared to other libraries, while maintaining high sensitivity and specificity. This design increases the dynamic range of CRISPR-Cas9 screens, allowing for its application in complex models and assays. MinLibCas9 is also backward compatible with existing datasets.
Article
Developmental Biology
Akaljot Singh, Holly M. Poling, Praneet Chaturvedi, Konrad Thorner, Nambirajan Sundaram, Daniel O. Kechele, Charlie J. Childs, Heather A. McCauley, Garrett W. Fisher, Nicole E. Brown, Jason R. Spence, James M. Wells, Michael A. Helmrath
Summary: The in vitro differentiation of pluripotent stem cells into human intestinal organoids (HIOs) is an effective method for creating complex three-dimensional intestinal structures. This study analyzed the developmental stages of HIO engraftment and found that HIO maturation closely resembles fetal human intestinal development. The use of single-nuclear RNA sequencing further validated these findings and solidified the value of transplanted HIOs as a human intestinal model system.
Article
Biochemical Research Methods
Jens Puschhof, Cayetano Pleguezuelos-Manzano, Adriana Martinez-Silgado, Ninouk Akkerman, Aurelia Saftien, Charelle Boot, Amy de Waal, Joep Beumer, Devanjali Dutta, Inha Heo, Hans Clevers
Summary: This protocol outlines methods for co-culturing human small intestinal and colon organoids with microbes, including microinjection and exposure to bacteria. It provides detailed protocols for assessing cell viability and growth kinetics, as well as spatial relationships using microscopy techniques. Considerations for evaluating the impact of bacteria on gene expression and mutations through sequencing are also discussed.
Article
Multidisciplinary Sciences
Rodrigo M. Florentino, Kazutoyo Morita, Nils Haep, Takashi Motomura, Ricardo Diaz-Aragon, Lanuza A. P. Faccioli, Alexandra Collin de l'Hortet, Zeliha Cetin, Carla Frau, Lawrence Vernetti, Anna-Klara Amler, Alexander Thomas, Tobias Lam, Lutz Kloke, Kazuki Takeishi, D. Lansing Taylor, Ira J. Fox, Alejandro Soto-Gutierrez
Summary: Advancements in cellular engineering and gene therapy allow for the production of human tissues with programmable genetically enhanced functions to model and treat specific diseases. This study successfully fabricated synthetic human liver tissues with programmable functions using CRISPR-Cas9 to control gene expression. The engineered liver tissues demonstrated enhanced functions compared to primary liver cells.
Article
Cell Biology
Shivohum Bahuguna, Siamak Redhai, Jun Zhou, Tianyu Wang, Fillip Port, Michael Boutros
Summary: The study evaluated the ability of the CRISPR-Cas9 system in inducing stem cell-derived tumors in the intestine of Drosophila. Perturbing Notch and BMP signaling increased proliferation of ISCs/EBs and led to tumor formation with different efficiencies. Continuous high expression of Cas9 in ISCs/EBs blocked age-dependent proliferation and prevented tumorigenesis when combined with specific gRNAs.
Review
Genetics & Heredity
Haruna Takeda
Summary: This review discusses the platform for functionally validating colorectal cancer driver genes using CRISPR-Cas9 in mouse intestinal tumor organoids. It highlights the application of mouse organoids in CRC research and the validation of CRC genes.
FRONTIERS IN GENETICS
(2021)
Article
Cell & Tissue Engineering
Xiaodan Wu, Xiantao Wang
Summary: Researchers have established a TBX20-knockout human embryonic stem cell line that retains stem cell-like features, pluripotency, a normal karyotype, and the ability to differentiate into all three germ layers in vivo. This cell line could be a valuable tool for studying the role of TBX20 in human development and its potential applications in regenerative medicine and disease modeling.
STEM CELL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Loretta Laszlo, Hedi Maczelka, Tamas Takacs, Anita Kurilla, Almos Tilajka, Laszlo Buday, Virag Vas, Agota Apati
Summary: This study established an embryonic stem cell model to investigate the role of Tks4 protein in different cell lineages. The loss of Tks4 was found to cause FTHS and alter cell lineage differentiation and maturation processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Ecology
Tae Young Ryu, Kwangho Kim, Tae-Su Han, Mi-Ok Lee, Jinkwon Lee, Jinhyeon Choi, Kwang Bo Jung, Eun-Jeong Jeong, Da Mi An, Cho-Rok Jung, Jung Hwa Lim, Jaeeun Jung, Kunhyang Park, Moo-Seung Lee, Mi-Young Kim, Soo Jin Oh, Keun Hur, Ryuji Hamamoto, Doo-Sang Park, Dae-Soo Kim, Mi-Young Son, Hyun-Soo Cho
Summary: The human microbiome has been found to play a crucial role in regulating colorectal cancer growth through the modulation of EHMT2 protein levels and TNFAIP1 gene expression. This study suggests that propionate and EHMT2 inhibitors may serve as therapeutic targets for colon cancer treatment, and there may be synergistic effects between EHMT2 inhibitors and the microbiome in CRC treatment.
Article
Oncology
Kunhyang Park, Kwangho Kim, Tae Young Ryu, Jinkwon Lee, Moo-Seung Lee, Mi-Young Son, Seon-Jin Lee, Young-Jun Park, Hyun-Soo Cho, Dae-Soo Kim
Summary: The present study used Gene Ontology analysis to investigate the biological responses of lung epithelial cells and fibroblasts following exposure to PM. The results suggested that PM may affect cell condition and may be associated with several human diseases.
MOLECULAR MEDICINE REPORTS
(2022)
Article
Cell Biology
Jung Hwa Lim, Dae Hun Kim, Kyung Hee Noh, Cho-Rok Jung, Hyun Mi Kang
Summary: This study identified epidermal progenitor cells that possess unlimited proliferation and multipotent differentiation capacity. These cells can form organotypic skin models and mimic the morphologic and biochemical processes of human epidermis. The proliferation and differentiation of these cells rely on the expression of Integrin beta 1 (ITGB1). Furthermore, the in vitro and in vivo wound healing capacity of these cells was examined.
CELL PROLIFERATION
(2022)
Article
Biochemistry & Molecular Biology
Hyun Mi Kang, Dae Hun Kim, Mijin Kim, Yoohong Min, Bohyeon Jeong, Kyung Hee Noh, Da Yong Lee, Hyun-Soo Cho, Nam-Soon Kim, Cho-Rok Jung, Jung Hwa Lim
Summary: This study discovered that the FBXL17-SPAST pathway is involved in the pathogenicity of hereditary spastic paraplegia (HSP) through loss of function and quantitative regulation. Targeting FBXL17 could provide new insights into HSP therapeutics.
CELL AND BIOSCIENCE
(2022)
Article
Engineering, Biomedical
Seul-Gi Lee, Ye-Ji Kim, Mi-Young Son, Min-Seok Oh, Jin Kim, Bokyeong Ryu, Kyu-Ree Kang, Jieun Baek, Gujin Chung, Dong Ho Woo, C-Yoon Kim, Hyung Min Chung
Summary: In response to the growing demand for 3D culture, we studied heart organoids. By creating self-organized HOs using human iPSCs, we demonstrated their ability to mimic cardiac structures and verified their mechanical/electrophysiological features through multiple analyses. The cardiovascular characteristics of HOs were maintained after in vivo transplantation.
Article
Multidisciplinary Sciences
Jeongmin Ha, Bum Suk Kim, Byungkuk Min, Juhyeon Nam, Jae-Geun Lee, Minhyung Lee, Byoung-Ha Yoon, Yoon Ha Choi, Ilkyun Im, Jung Sun Park, Hyosun Choi, Areum Baek, Sang Mi Cho, Mi-Ok Lee, Ki-Hoan Nam, Ji Young Mun, Mirang Kim, Seon-Young Kim, Mi Young Son, Yong-Kook Kang, Jeong-Soo Lee, Jong Kyoung Kim, Janghwan Kim
Summary: The cytoskeletal linker protein desmoplakin (Dsp) plays a crucial role in both in vitro cellular reprogramming and tissue regeneration. Knockdown of Dsp impairs the formation of intermediate cells during cellular reprogramming and tissue regeneration. This study suggests a potential evolutionary link mediated by Dsp between cellular reprogramming in mammals and tissue regeneration in lower vertebrates, and the intermediate cells may provide alternative approaches for mammalian regenerative therapy.
Article
Gastroenterology & Hepatology
Hana Lee, Kwang Bo Jung, Ohman Kwon, Ye Seul Son, Eunho Choi, Won Dong Yu, Naeun Son, Jun Hyoung Jeon, Hana Jo, Haneol Yang, Yeong Rak Son, Chan-Seok Yun, Hyun-Soo Cho, Sang Kyu Kim, Dae-Soo Kim, Doo-Sang Park, Mi-Young Son
Summary: This study investigates the modulatory capacity of a newly isolated probiotic strain (DS0384) on early intestinal development. They found that DS0384 accelerated the maturation of fetal intestines and promoted intestinal stem cell proliferation by secreting a specific metabolite (NCG). The results suggest that DS0384 has potential probiotic properties and therapeutic applications for early gut development disorders.
Article
Biochemistry & Molecular Biology
Hae-Ri Lee, Soo Kim, Sungho Shin, Seon-Yeong Jeong, Dae-Won Lee, Sun-Ung Lim, Ji Yeon Kang, Mi-Young Son, Cheolju Lee, Kyung-Rok Yu, Myungshin Kim, Il-Hoan Oh
Summary: In this study, the transition from primary MSCs to iMSCs was characterized by increased proliferative activity and variations in differentiation potential. iMSCs exhibited unique gene and protein expression patterns, resembling pericyte-like cells, and showed enhanced self-renewal and immune suppression capabilities.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Ilkyu Park, Nakyoung Kim, Sugi Lee, Kunhyang Park, Mi-Young Son, Hyun-Soo Cho, Dae-Soo Kim
Summary: The timely diagnosis of different stages in NAFLD is crucial for disease treatment and reversal. In this study, we identified differentially expressed genes in NAFLD patients compared to healthy controls and determined their predictive power. We also found significant differential expression of candidate genes in liver cancer that may influence patient survival.
Article
Engineering, Biomedical
Hyunah Ahn, Younghak Cho, Geun-Tae Yun, Kwang Bo Jung, Wonji Jeong, Yesol Kim, Mi-Young Son, Eunjung Lee, Sung Gap Im, Hee-Tae Jung
Summary: This study presents a hierarchical structure composed of nano-pillars on micro-wrinkles for enhancing cardiomyocyte maturation. The responses of cardiomyocytes on hierarchical topography are systematically investigated. The combination of nano-pillars and micro-wrinkles significantly enhances the maturation of cardiomyocytes.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Kwangho Kim, Tae Young Ryu, Jinkwon Lee, Mi-Young Son, Dae-Soo Kim, Sang Kyum Kim, Hyun-Soo Cho
Summary: This study identified EHMT1 as an overexpressed gene in colorectal cancer (CRC) and demonstrated that knocking down EHMT1 expression suppressed cell growth and induced apoptosis in CRC cell lines. Further analysis revealed that EHMT1 regulates cell apoptosis through the CHOP gene. These findings suggest EHMT1 as a potential therapeutic target for CRC treatment.
MOLECULES AND CELLS
(2022)
Article
Biochemistry & Molecular Biology
Seung-Ho Park, Sung-Jin Yoon, Song Choi, Jaeeun Jung, Jun-Young Park, Young-Ho Park, Jinho Seo, Jungwoon Lee, Moo-Seung Lee, Seon-Jin Lee, Mi-Young Son, Young-Lai Cho, Jang-Seong Kim, Hyo Jin Lee, Jinyoung Jeong, Dae-Soo Kim, Young-Jun Park
Summary: The study reveals that exposure to particulate matter pollutants can induce immune cells to secrete HBEGF, leading to a more invasive state in cancer cells. This finding helps uncover the mechanism by which PM promotes cancer metastasis.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Jongjin Park, Dong Gwang Lee, Na Geum Lee, Min-Gi Kwon, Yeon Sung Son, Mi-Young Son, Kwang-Hee Bae, Jangwook Lee, Jong-Gil Park, Nam-Kyung Lee, Jeong-Ki Min
Summary: In this study, researchers developed a monoclonal antibody K312 that can distinguish undifferentiated pluripotent stem cells (PSCs) from differentiated PSC progeny. By targeting with K312, pluripotent cells can be depleted from differentiated PSC progeny, effectively preventing teratoma formation.
Article
Cell & Tissue Engineering
Ohman Kwon, Won Dong Yu, Ye Seul Son, Kwang Bo Jung, Hana Lee, Mi-Young Son
Summary: This study develops a reliable culture method for 3D intestinal spheroids (InSexp) that can expand and maintain human intestinal stem cells (ISCs). By activating the WNT pathway, the InSexp can rapidly expand and be passaged. These findings contribute to the development of scalable culture systems for studying ISC biology.
INTERNATIONAL JOURNAL OF STEM CELLS
(2022)