Article
Oncology
Jae-Il Choi, Sung Ill Jang, Jaehyun Hong, Chul Hoon Kim, Soon Sung Kwon, Joon Seong Park, Jong-Baeck Lim
Summary: In this study, it was demonstrated that CD44(+), CD24(+) and EpCAM(+) cancer-initiating cells (CICs) were enriched in patient-derived organoids of PDAC. CD44-expressing CICs formed lumen structures within the organoids. Additionally, CD44(-) cancer cells from the organoids could re-form organoids and be re-programed as CD44-expressing CICs. The study also showed that the maintenance of CICs in PDAC organoids was mediated by interactions with endothelial cells through Wnt and Notch signaling pathways.
Review
Toxicology
Atsushi Masui, Toyohiro Hirai, Shimpei Gotoh
Summary: The absence of in vitro platforms for human pulmonary toxicology studies is a growing concern. Recent advances in culture methods, specifically human pluripotent stem cell-derived lung epithelial organoid culture systems, have provided potential solutions. These advancements have allowed for the in vitro recapitulation of genetic lung diseases and the evaluation of the effectiveness and toxicity of therapeutic agents, bridging the gap between bench and bedside.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Biochemical Research Methods
Julia Vallverdu, Raquel A. Martinez Garcia de la Torre, Inge Mannaerts, Stefaan Verhulst, Ayla Smout, Mar Coll, Silvia Arino, Teresa Rubio-Tomas, Beatriz Aguilar-Bravo, Celia Martinez-Sanchez, Delia Blaya, Catherine M. Verfaillie, Leo A. van Grunsven, Pau Sancho-Bru
Summary: Human iPSCs are differentiated into HSCs with growth factors for in vitro modeling. The protocol yields iPSC-HSCs with phenotypic and functional characteristics of primary HSCs, suitable for high-throughput in vitro studies. Coculturing iPSC-HSCs with hepatocytes allows for the formation of 3D hepatic spheroids, enabling modeling and drug screening studies.
Article
Cell Biology
Jin Wook Hwang, Christophe Desterke, Julien Loisel-Duwattez, Frank Griscelli, Annelise Bennaceur-Griscelli, Ali G. Turhan
Summary: Cells expressing HSC transcriptome were found in the human fetal kidney, and similar expression features were observed in iPSC-derived kidney organoids. These findings support the presence of HSC markers in the human kidney. Further investigation is needed to understand the mechanisms behind the appearance of these cells with similar transcriptional features.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Medicine, General & Internal
Chang Liu, Xing Feng, Guoping Li, Priyanka Gokulnath, Junjie Xiao
Summary: Human pluripotent stem cell (hPSC) technology provides abundant opportunities for disease modeling. Cardiomyocytes derived from hPSCs are efficient tools for studying cardiac diseases, drug screening, and pathological mechanisms. This review discusses the advantages and limitations of the 2D hPSC-cardiomyocyte system and introduces recent developments in 3D culture platforms derived from hPSCs.
Article
Biology
Mei-Ling Gao, Xiao Zhang, Fang Han, Jia Xu, Si-Jian Yu, Kangxin Jin, Zi-Bing Jin
Summary: Researchers have successfully differentiated human pluripotent stem cells into brain-induced microglia-like cells and derived resident retinal microglia in vitro. This study provides a new source of human retinal microglia for developmental and disease studies and regenerative therapeutics.
SCIENCE CHINA-LIFE SCIENCES
(2022)
Article
Gastroenterology & Hepatology
Tadahiro Shinozawa, Masaki Kimura, Yuqi Cai, Norikazu Saiki, Yosuke Yoneyama, Rie Ouchi, Hiroyuki Koike, Mari Maezawa, Ran-Ran Zhang, Andrew Dunn, Autumn Ferguson, Shodai Togo, Kyle Lewis, Wendy L. Thompson, Akihiro Asai, Takanori Takebe
Summary: This study established a screening model based on human liver organoids (HLO) for analyzing drug-induced liver injury (DILI) pathology, providing unique advantages at the organoid resolution. Through this model, a multi-readout organoid analysis was successfully developed to measure viability, cholestatic and/or mitochondrial toxicity, showing high predictive values for marketed drugs.
Article
Oncology
Lei Du, Qi Cheng, Hao Zheng, Jinming Liu, Lei Liu, Quan Chen
Summary: This review provides an overview of current progress in colorectal cancer stem cell (CCSC) studies, including specific surface markers, intrinsic signaling pathways, and tumor organoid models. The review highlights the potential of targeting CCSCs through monoclonal antibodies, natural or synthetic compounds, or immunotherapy. Combinatory approaches targeting the stemness network may be important for eradicating cancer, considering the heterogeneity and plasticity of CSCs.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Po-Yu Liang, Yun Chang, Gyuhyung Jin, Xiaojun Lian, Xiaoping Bao
Summary: Heart diseases are the leading cause of death worldwide. Researchers have found that by manipulating signaling pathways, more mature cardiac organoids can be generated for studying cardiovascular development and diseases.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Review
Cell & Tissue Engineering
Yuqin Liang, Xihao Sun, Chunwen Duan, Shibo Tang, Jiansu Chen
Summary: This paper focuses on the status of patient-derived iPSCs and organoids in modeling and exploring inherited retinal diseases (IRDs), as well as the challenges of translating laboratory research to clinical application. The importance of human iPSCs and organoids in combination with emerging technologies is highlighted.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Ha-Rim Seo, Hyeong-Jun Han, Youngsun Lee, Young-Woock Noh, Seung-Ju Cho, Jung-Hyun Kim
Summary: This study successfully generated alveolar organoids containing functional macrophages using biomimetic strategies. These improved organoids exhibit higher levels of inflammatory factors and can produce chemotactic factor IL-8, making them a valuable tool for studying inflammatory pulmonary diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Engineering, Biomedical
Hyemin Kim, Ilkyun Im, Jang Su Jeon, Eun-Hye Kang, Hyang-Ae Lee, Seongyea Jo, Ji-Woo Kim, Dong-Hun Woo, Young Jae Choi, Hyo Jin Kim, Ji-Seok Han, Byoung-Seok Lee, Jong-Hoon Kim, Sang Kyum Kim, Han-Jin Park
Summary: This study aims to generate liver organoids with high drug metabolic ability using human pluripotent stem cells. The fully differentiated organoids exhibit cellular polarity, hepatobiliary structures, and remarkable drug metabolic function. They can also successfully model Wilson's disease and provide an advanced tool for studying hepatic drug metabolism and diseases.
Article
Chemistry, Multidisciplinary
Chia-Lin Chen, Juan Carlos Hernandez, Dinesh Babu Uthaya Kumar, Tatsuya Machida, Stanley M. Tahara, Anthony El-Khoueiry, Meng Li, Vasu Punj, Suresh Kumar Swaminathan, Ameya Kirtane, Yibu Chen, Jayanth Panyam, Keigo Machida
Summary: The improvement of drug selectivity, toxicity, and reduced recurrence of tumors from tumor-initiating stem-like cells is essential for effective cancer therapy. Through high-throughput screens, a combination of histone deacetylase (HDAC) inhibitor(s) and all-trans retinoic acid (ATRA) has been found to effectively inhibit TIC growth. This combined treatment reduces Toll-like receptors (TLR) and stemness genes, leading to loss of self-renewal property of TICs.
Editorial Material
Cell Biology
Justin A. Powers, Iok In Christine Chio
Summary: In a recent study, researchers found a connection between ECM stiffness and the redox response of disseminated tumor cells. Soft ECM was found to promote DRP1-mediated mitochondrial fission and an NRF2-dependent antioxidant response.
NATURE CELL BIOLOGY
(2022)
Article
Cell Biology
Neus Bota-Rabassedas, Priyam Banerjee, Yichi Niu, Wenjian Cao, Jiayi Luo, Yuanxin Xi, Xiaochao Tan, Kuanwei Sheng, Young-Ho Ahn, Sieun Lee, Edwin Roger Parra, Jaime Rodriguez-Canales, Jacob Albritton, Michael Weiger, Xin Liu, Hou-Fu Guo, Jiang Yu, B. Leticia Rodriguez, Joshua J. A. Firestone, Barbara Mino, Chad J. Creighton, Luisa M. Solis, Pamela Villalobos, Maria Gabriela Raso, Daniel W. Sazer, Don L. Gibbons, William K. Russell, Gregory D. Longmore, Ignacio I. Wistuba, Jing Wang, Harold A. Chapman, Jordan S. Miller, Chenghang Zong, Jonathan M. Kurie
Summary: Cancer cells alter cancer-associated fibroblasts through specific secretory programs and repulsion processes, promoting cancer cell metastasis and sensitivity to pro-metastatic signals from fibroblasts.
Article
Biochemistry & Molecular Biology
Johanna Theruvath, Marie Menard, Benjamin A. H. Smith, Miles H. Linde, Garry L. Coles, Guillermo Nicolas Dalton, Wei Wu, Louise Kiru, Alberto Delaidelli, Elena Sotillo, John L. Silberstein, Anna C. Geraghty, Allison Banuelos, Molly Thomas Radosevich, Shaurya Dhingra, Sabine Heitzeneder, Aidan Tousley, John Lattin, Peng Xu, Jing Huang, Nicole Nasholm, Andy He, Tracy C. Kuo, Emma R. B. Sangalang, Jaume Pons, Amira Barkal, Rachel E. Brewer, Kristopher D. Marjon, Jose G. Vilches-Moure, Payton L. Marshall, Ricardo Fernandes, Michelle Monje, Jennifer R. Cochran, Poul H. Sorensen, Heike E. Daldrup-Link, Irving L. Weissman, Julien Sage, Ravindra Majeti, Carolyn R. Bertozzi, William A. Weiss, Crystal L. Mackall, Robbie G. Majzner
Summary: The combination of anti-GD2 and CD47 blockade demonstrates robust anti-tumor activity in mouse models, particularly effective against neuroblastoma, osteosarcoma, and small-cell lung cancer.
Article
Multidisciplinary Sciences
Yu-Chen Lo, Timothy J. Keyes, Astraea Jager, Jolanda Sarno, Pablo Domizi, Ravindra Majeti, Kathleen M. Sakamoto, Norman Lacayo, Charles G. Mullighan, Jeffrey Waters, Bita Sahaf, Sean C. Bendall, Kara L. Davis
Summary: The authors present CytofIn, a data integration strategy that can integrate mass cytometry datasets from the public domain, enabling the analysis and comparison of immune features associated with oncology across multiple cancer datasets.
NATURE COMMUNICATIONS
(2022)
Review
Hematology
Asiri Ediriwickrema, Andrew J. Gentles, Ravindra Majeti
Summary: The era of genomic medicine has advanced AML research, but AML remains a lethal cancer due to its complex and plastic cellular architecture. Single-cell genomics has the potential to address the challenges posed by cellular heterogeneity and provide unique opportunities in AML research.
Letter
Hematology
Maximilian Stahl, Omar Abdel-Wahab, Andrew H. Wei, Michael R. Savona, Mina L. Xu, Zhuoer Xie, Justin Taylor, Daniel Starczynowski, Guillermo F. Sanz, David A. Sallman, Valeria Santini, Gail J. Roboz, Mrinal M. Patnaik, Eric Padron, Olatoyosi Odenike, Aziz Nazha, Stephen D. Nimer, Ravindra Majeti, Richard F. Little, Steven Gore, Alan F. List, Vijay Kutchroo, Rami S. Komrokji, Tae Kon Kim, Nina Kim, Christopher S. Hourigan, Robert P. Hasserjian, Stephanie Halene, Elizabeth A. Griffiths, Peter L. Greenberg, Maria Figueroa, Pierre Fenaux, Fabio Efficace, Amy E. DeZern, Matteo G. Della Porta, Naval G. Daver, Jane E. Churpek, Hetty E. Carraway, Andrew M. Brunner, Uma Borate, John M. Bennett, Rafael Bejar, Jacqueline Boultwood, Sanam Loghavi, Jan Philipp Bewersdorf, Uwe Platzbecker, David P. Steensma, Mikkael A. Sekeres, Rena J. Buckstein, Amer M. Zeidan
Article
Oncology
Daniel Thomas, Manhong Wu, Yusuke Nakauchi, Ming Zheng, Chloe A. L. Thompson-Peach, Kelly Lim, Niklas Landberg, Thomas Koehnke, Nirmal Robinson, Satinder Kaur, Monika Kutyna, Melissa Stafford, Devendra Hiwase, Andreas Reinisch, Gary Peltz, Ravindra Majeti
Summary: Isocitrate dehydrogenase 1 and 2 (IDH) mutations drive the production of (R)-2-hydroxyglutarate (2HG) in multiple cancers. A lipid synthesis enzyme, acetyl CoA carboxylase 1 (ACC1), was identified as a synthetic lethal target in mutant IDH1 (mIDH1) cancers. mIDH1 AML exhibits specific metabolic alterations, such as reduced fatty acids and a switch to fatty acid oxidation. Targeting ACC1 inhibits the growth of mIDH1 cancers and improves the sensitivity of mIDH1 AML to venetoclax.
Article
Oncology
Miles H. Linde, Amy C. Fan, Thomas Koehnke, Aaron C. Trotman-Grant, Sarah F. Gurev, Paul Phan, Feifei Zhao, Naomi L. Haddock, Kevin A. Nuno, Eric J. Gars, Melissa Stafford, Payton L. Marshall, Christopher G. Dove, Ian L. Linde, Niklas Landberg, Lindsay P. Miller, Robbie G. Majzner, Tian Yi Zhang, Ravindra Majeti
Summary: Therapeutic cancer vaccination aims to activate tumor-reactive T cells for recognizing tumor-associated antigens (TAA) and eliminating malignant cells. The study proposes a cancer vaccination approach using myeloid-lineage reprogramming to convert cancer cells into tumor-reprogrammed antigen-presenting cells (TR-APC). The results demonstrate the effectiveness of TR-APCs in inducing clonal expansion of cancer-specific T cells, establishing immune memory, and promoting leukemia eradication.
Article
Oncology
Andriana G. Kotini, Saul Carcamo, Nataly Cruz-Rodriguez, Malgorzata Olszewska, Tiansu Wang, Deniz Demircioglu, Chan-Jung Chang, Elsa Bernard, Mark P. Chao, Ravindra Majeti, Hanzhi Luo, Michael G. Kharas, Dan Hasson, Eirini P. Papapetrou
Summary: A reprogramming method tailored to cancer cells was developed to generate iPSCs from AML patients, and the resulting iPSC-derived leukemias faithfully mimicked the primary patient-matched xenografts.
BLOOD CANCER DISCOVERY
(2023)
Article
Medicine, Research & Experimental
Amy C. Fan, Yusuke Nakauchi, Lawrence Bai, Armon Azizi, Kevin A. Nuno, Feifei Zhao, Thomas Koehnke, Daiki Karigane, David Cruz-Hernandez, Andreas Reinisch, Purvesh Khatri, Ravindra Majeti
Summary: This study reveals the dependence of RUNX1-mutant leukemias on IL-3/JAK/STAT signaling, which can potentially be targeted using JAK inhibitors.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Meeting Abstract
Oncology
James Chen, Lisa Johnson, Kelly McKenna, Timothy Choi, Jiaqi Duan, Dongdong Feng, Jonathan Tsai, Natalia Garcia-Martin, Kavitha Sompalli, Roy Maute, Paresh Vyas, Ravindra Majeti, Chris Takimoto, Jie Liu, Giridharan Ramsingh, Mark Chao, Jens-Peter Volkmer, Irving Weissman
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2022)
Meeting Abstract
Oncology
Nathaniel W. Mabe, Min Huang, Daniel A. Schaefer, Guillermo N. Dalton, Giulia Digiovanni, Gabriela Alexe, Anna C. Geraghty, Delan Khalid, Marius M. Mader, Michal Sheffer, Miles H. Linde, Nghi Ly, Maria Caterina Rotiroti, Benjamin A. H. Smith, Marius Wernig, Carolyn R. Bertozzi, Michelle Monje, Constantine Mitsiades, Ravindra Majeti, Ansuman T. Satpathy, Kimberly Stegmaier, Robbie G. Majzner
Meeting Abstract
Hematology
Amy Fan, Armon Azizi, Kevin Nuno, Yusuke Nakauchi, Feifei Zhao, David Cruz-Hernandez, Andreas Reinisch, Ravindra Majeti
EXPERIMENTAL HEMATOLOGY
(2022)
Meeting Abstract
Oncology
James Yuhtyng Chen, Lisa Johnson, Kelly Marie McKenna, Timothy S. Choi, Jiaqi Duan, Dongdong Feng, Jonathan M. Tsai, Natalia Garcia-Martin, Kavitha Sompalli, Roy Maute, Paresh Vyas, Ravindra Majeti, Chris H. M. Takimoto, Jie Liu, Giridharan Ramsingh, Mark Chao, Jens-Peter Volkmer, Irving L. Weissman
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Yusuke Nakauchi, Armon Azizi, Daniel Thomas, M. Ryan Corces, Andreas Reinisch, Rajiv Sharma, David Cruz Hernandez, Thomas Kohnke, Daiki Karigane, Amy Fan, Daniel Martinez-Krams, Melissa Stafford, Satinder Kaur, Ritika Dutta, Paul Phan, Asiri Ediriwickrema, Erin McCarthy, Yuhong Ning, Tierney Phillips, Christopher K. Ellison, Gulfem D. Guler, Anna Bergamaschi, Chin -Jen Ku, Samuel Levy, Ravindra Majeti
Summary: The study reveals that 5-hydroxymethylation profiles are cell type-specific and linked to transcriptional abundance and chromatin accessibility in human hematopoiesis. TET2 loss results in abnormal growth and differentiation phenotypes and disrupts 5hmC and transcriptional landscapes. Treatment with ascorbate or azacitidine restores 5hmC profiles and corrects aberrant phenotypes in TET2 KO HSPCs.
BLOOD CANCER DISCOVERY
(2022)
Article
Oncology
Anna P. Hnatiuk, Arne A. N. Bruyneel, Dhanir Tailor, Mallesh Pandrala, Arpit Dheeraj, Wenqi Li, Ricardo Serrano, Dries A. M. Feyen, Michelle M. Vu, Prashila Amatya, Saloni Gupta, Yusuke Nakauchi, Isabel Morgado, Volker Wiebking, Ronglih Liao, Matthew H. Porteus, Ravindra Majeti, Sanjay Malhotra, Mark Mercola
Summary: This study developed safer analogs of Ponatinib that retain potency against T315I BCR-ABL kinase activity and suppress T315I mutant CML tumor growth while significantly decreasing cardiotoxicity. The compounds showed improved safety in both in vitro and in vivo models.
Article
Oncology
Nathaniel W. Mabe, Min Huang, Guillermo N. Dalton, Gabriela Alexe, Daniel A. Schaefer, Anna C. Geraghty, Amanda L. Robichaud, Amy S. Conway, Delan Khalid, Marius M. Mader, Julia A. Belk, Kenneth N. Ross, Michal Sheffer, Miles H. Linde, Nghi Ly, Winnie Yao, Maria Caterina Rotiroti, Benjamin A. H. Smith, Marius Wernig, Carolyn R. Bertozzi, Michelle Monje, Constantine S. Mitsiades, Ravindra Majeti, Ansuman T. Satpathy, Kimberly Stegmaier, Robbie G. Majzner
Summary: Mabe et al. found that the levels of GD2 are associated with lineage plasticity in neuroblastoma, and they identified ST8SIA1 as the critical enzyme in GD2 synthesis. Inhibition of EZH2 in mesenchymal neuroblastoma cells increases ST8SIA1 expression, synergizing with anti-GD2 antibodies. However, there is a lack of understanding about the mechanisms of resistance to anti-GD2 therapy. This study reveals that reduced GD2 expression is significantly correlated with the mesenchymal cell state in neuroblastoma, and a forced adrenergic-to-mesenchymal transition (AMT) leads to GD2 downregulation and resistance to anti-GD2 antibody. The pharmacologic inhibition of EZH2 results in epigenetic rewiring of mesenchymal neuroblastoma cells, enabling re-expression of ST8SIA1, restoration of GD2 surface expression, and sensitivity to anti-GD2 antibody.