Article
Multidisciplinary Sciences
Mikael Sandstedt, Kristina Vukusic, Benjamin Ulfenborg, Marianne Jonsson, Lillemor Mattsson Hulten, Goran Dellgren, Anders Jeppsson, Jane Synnergren, Joakim Sandstedt
Summary: Cardiomyocyte proliferation is the main source of new cardiomyocytes in adults. This study discovered SSEA4+CD34- cells in the adult human heart, which may serve as immature cycling cardiomyocytes and play a role in endogenous cardiac regeneration.
Article
Oncology
Changlin Yang, Guimei Tian, Mariana Dajac, Andria Doty, Shu Wang, Ji-Hyun Lee, Maryam Rahman, Jianping Huang, Brent A. Reynolds, Matthew R. Sarkisian, Duane Mitchell, Loic P. Deleyrolle
Summary: This study reveals the diversity of cell types and dynamic behaviors in glioblastoma, particularly the heterogeneity between slow-cycling cells and cells defined by the expression of stem cell markers. The findings shed light on the potential mechanisms underlying tumor resilience and treatment resistance, and provide insights for the development of precision and effective therapies for brain cancer.
Article
Cell Biology
Fangfang Wang, Zhang Dan, Hongmei Luo, Jingcao Huang, Yushan Cui, Hong Ding, Juan Xu, Zhimei Lin, Yuhan Gao, Xinyu Zhai, Yan Yang, Ying Qu, Li Zhang, Fengjiao Chen, Qiang Wang, Xin Wang, Yu Feng, Ting Liu, Qing Yi, Ting Niu, Yuhuan Zheng
Summary: Drug-resistance is a major problem in multiple myeloma (MM) patients. This study reveals that activated-leukocyte-cell-adhesion-molecule (ALCAM) regulates MM side population (SP)-mediated drug-resistance through the ALCAM-EGF/EGFR axis. EGFR activation promotes the SP ratio, while ALCAM inhibits EGFR downstream signaling in MM cells. SP MM cells have a higher number of mitochondria and interference of mitochondrial function inhibits SP-genesis. Combination therapy with an anti-MM agent and EGFR inhibitor gefitinib improves MM therapeutic efficacy and prolongs survival in MM-bearing mice.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Alena Kalinina, Catherine Gnyra, Vera Tang, Yingben Xue, Diane C. Lagace
Summary: The use of DNA-binding dyes in stem cell research is significant for isolating specific cell populations. In this study, a distinct side population of cells was identified in the mouse brain using a DNA-binding dye, and these cells showed sensitivity to ABC transporter inhibitors. Furthermore, the majority of these cells expressed CD31 and were not adult neural stem cells.
Review
Cell & Tissue Engineering
Li Liu, Lilong Zhang, Chunlei Li, Zhendong Qiu, Tianrui Kuang, Zhongkai Wu, Wenhong Deng
Summary: This review summarizes recent progress in the identification of hormones associated with intestinal stem cells, which can promote or prevent their development. Several hormones, such as thyroid hormone, glucagon-like peptide-2, androgens, insulin, leptin, growth hormone, corticotropin-releasing hormone, and progastrin, promote the development of intestinal stem cells, while somatostatin and melatonin prevent their proliferation. This provides potential new therapeutic targets for the diagnosis and treatment of intestinal illnesses.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Medicine, Research & Experimental
Yuning Jackie Tang, Vijitha Puviindran, Yu Xiang, Yasuhito Yahara, Hongyuan Zhang, Puviindran Nadesan, Yarui Diao, David G. Kirsch, Benjamin A. Alman
Summary: This study found that in sarcomas, non-SP cells can give rise to SP cells with enhanced tumor-propagating potential, supporting the concept that non-TPCs can generate TPCs. However, ablation of the SP population did not impede tumor growth or self-renewal, indicating that sarcoma SP represent a dynamic cell state.
Article
Multidisciplinary Sciences
Keila Alvarado-Estrada, Lina Marenco-Hillembrand, Sushila Maharjan, Valerio Luca Mainardi, Yu Shrike Zhang, Natanael Zarco, Paula Schiapparelli, Hugo Guerrero-Cazares, Rachel Sarabia-Estrada, Alfredo Quinones-Hinojosa, Kaisorn L. Chaichana
Summary: Cancer cells circulating in the blood vessels can survive and lead to increased metastatic disease under the pressure of circulation. Specific transition phenotypes of cancer cells play a critical role in their survival and metastatic potential in the circulatory system.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Daniel Jun-Kit Hu, Jina Yun, Justin Elstrott, Heinrich Jasper
Summary: The study demonstrates that enteroendocrine cells coordinate stem cell migration towards sites of injury in the Drosophila intestine by activating non-canonical Wnt signaling. This coordination is crucial for efficient tissue repair during injury.
NATURE COMMUNICATIONS
(2021)
Review
Environmental Sciences
Shao-jie Liang, Xiu-qi Wang
Summary: This review provides insights into the presence and harmful effects of deoxynivalenol (DON), one of the most widely occurring mycotoxins, on the animal husbandry industry and human health. It focuses on the adverse effects of DON on intestinal stem cells (ISCs) and how it induces oxidative stress. Strategies for reducing the harm of DON are summarized, including the regulation of microbiota, molecular docking, and modulation of the redox status through the manipulation of Keap1 protein expression and single-cell sequencing.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2023)
Article
Cell Biology
Francesca Casciaro, Silvia Zia, Mattia Forcato, Manuela Zavatti, Francesca Beretti, Emma Bertucci, Andrea Zattoni, Pierluigi Reschiglian, Francesco Alviano, Laura Bonsi, Matilde Yung Follo, Marco Demaria, Barbara Roda, Tullia Maraldi
Summary: This study utilized Celector® technology to classify and characterize hAFSCs, uncovering deep intra-population differences and validating their impact on stemness properties. The results suggest the importance of selecting cellular fractions with the highest potential for use in regenerative medicine.
Article
Oncology
Paraskevi Mallini, Miaojuan Chen, Kamilla Mahkamova, Thomas W. J. Lennard, Yue Pan, Dan Wei, Katherine Stemke-Hale, John A. Kirby, Gendie E. Lash, Annette Meeson
Summary: Epithelial-to-mesenchymal transition (EMT) plays a vital role in regulating cancer cell behavior, allowing them to acquire stem cell characteristics and become more migratory and invasive. EMT can be driven by various mechanisms, such as the TGF-beta 1 signaling pathway and/or hypoxia. This study investigated the effects of CoCl2 exposure and TGF-beta-induced EMT on side population (SP) cells of breast cancer cell lines. The results showed contrasting effects on SP cells, suggesting the involvement of ER(x) expression and TGFB-RII in regulating SP cell behavior.
Article
Multidisciplinary Sciences
Ningbo Wu, Hongxiang Sun, Xiaoyun Zhao, Yao Zhang, Jianmei Tan, Yuanyuan Qi, Qun Wang, Melissa Ng, Zhaoyuan Liu, Lingjuan He, Xiaoyin Niu, Lei Chen, Zhiduo Liu, Hua-Bing Li, Yi Arial Zeng, Manolis Roulis, Dou Liu, Jinke Cheng, Bin Zhou, Lai Guan Ng, Duowu Zou, Youqiong Ye, Richard A. Flavell, Florent Ginhoux, Bing Su
Summary: The study identified a subset of intestinal stromal cells, MRISCs, as the primary cellular source of WNT agonist R-spondin 1 following intestinal injury in mice. These MRISCs are located at the bases of colon crypts, maintain LGR5(+) intestinal stem cells, and protect against acute intestinal damage through enhanced R-spondin 1 production. The mechanism involves a reactive oxygen species (ROS)-MAP3K2-ERK5-KLF2 axis to augment WNT signaling for intestinal regeneration.
Article
Medicine, Research & Experimental
Eberhard Korsching, Julian Matschke, Marc Hotfilder
Summary: This study provides a comprehensive analysis of alternative splicing in an Ewing model cell line carrying the EWSR1-ERG fusion gene. The findings contribute to a systematic understanding of the whole transcriptome of Ewing sarcoma and reveal insights into the differences between EWSR1-ERG and EWSR1-FLI1. These findings are important for both clinical procedures and basic mechanistic research.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2022)
Review
Cell Biology
Kai-Xuan Wang, Wen-Wen Cui, Xu Yang, Ai-Bin Tao, Ting Lan, Tao-Sheng Li, Lan Luo
Summary: Radiation therapy for cancers can cause damage to healthy cells and lead to side effects, calling for promising treatment strategies to mitigate the damage. Recent attention has focused on stem cell-based therapy, with mesenchymal stem cells being extensively applied due to their ease of access and diverse functions.
Article
Biochemistry & Molecular Biology
Francesca Casciaro, Francesca Beretti, Martina Gatti, Giuseppe Persico, Emma Bertucci, Marco Giorgio, Tullia Maraldi
Summary: Human amniotic fluid cells (hAFSCs) are a heterogeneous population with stem cell characteristics. This study compares the gene expression profiles of adherent amniotic fluid cells and their c-Kit(+) subpopulation through single-cell and bulk RNAseq analysis. Differences in cellular distribution, pathways related to stemness, and secretome composition were identified between the two populations. Selecting c-Kit positive fractions with higher potential could be important in regenerative medicine applications.
Article
Gastroenterology & Hepatology
S. E. Duff, C. L. F. Battersby, R. J. Davies, L. Hancock, J. Pipe, S. Buczacki, J. Kinross, A. G. Acheson, C. J. Walsh
COLORECTAL DISEASE
(2020)
Article
Multidisciplinary Sciences
Santiago Uribe-Lewis, Thomas Carroll, Suraj Menon, Anna Nicholson, Piotr J. Manasterski, Douglas J. Winton, Simon J. A. Buczacki, Adele Murrell
SCIENTIFIC REPORTS
(2020)
Letter
Surgery
Mahnaz Darvish-Damavandi, James Laycock, Christopher Ward, Milou S. van Driel, Mae A. Goldgraben, Simon J. A. Buczacki
BRITISH JOURNAL OF SURGERY
(2020)
Article
Cell Biology
Rachael E. Clifford, Naren Govindarajah, David Bowden, Paul Sutton, Mark Glenn, Mahnaz Darvish-Damavandi, Simon Buczacki, Ultan McDermott, Zdzislaw Szulc, Besim Ogretmen, Jason L. Parsons, Dale Vimalachandran
Review
Oncology
Dedrick Kok Hong Chan, Simon James Alexander Buczacki
Summary: Colorectal cancer is a global burden, characterized by an initial explosion of genetic diversity followed by neutral dynamics. Understanding the interplay between clonal populations during neutral evolution provides insights into the roles of driver genes in the progression from normal colonic epithelium to adenoma and carcinoma. Recent advances have focused on genetic, transcriptomic, and proteomic factors, as well as the ecological and evolutionary processes that contribute to cancer development.
Article
Oncology
Nikhil Lal, Dedrick Kok Hong Chan, Minn E. Ng, Louis Vermeulen, Simon James Alexander Buczacki
Summary: High lymph node (LN) yield is predictive of overall and disease-free survival in non-metastatic colon cancer. There is no association between higher LN yield and increasing nodal positivity, but it is strongly linked with gene expression changes associated with the adaptive and dendritic cell immune response, especially in node-negative cancers. These findings were validated in an independent dataset.
BRITISH JOURNAL OF CANCER
(2022)
Editorial Material
Gastroenterology & Hepatology
Dedrick Kok Hong Chan, Simon James Alexander Buczacki
COLORECTAL DISEASE
(2022)
Article
Multidisciplinary Sciences
Bernard C. H. Lee, Philip S. Robinson, Tim H. H. Coorens, Helen H. N. Yan, Sigurgeir Olafsson, Henry Lee-Six, Mathijs A. Sanders, Hoi Cheong Siu, James Hewinson, Sarah S. K. Yue, Wai Yin Tsui, Annie S. Y. Chan, Anthony K. W. Chan, Siu Lun Ho, Peter J. Campbell, Inigo Martincorena, Simon J. A. Buczacki, Siu Tsan Yuen, Suet Yi Leung, Michael R. Stratton
Summary: The study shows that normal tissues in Lynch Syndrome (LS) patients are genomically stable, while ancestor cells of neoplastic tissues undergo multiple cycles of clonal evolution. This highlights important differences in the pathogenesis of LS from other colorectal cancer predisposition syndromes.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Philip S. Robinson, Laura E. Thomas, Federico Abascal, Hyunchul Jung, Luke M. R. Harvey, Hannah D. West, Sigurgeir Olafsson, Bernard C. H. Lee, Tim H. H. Coorens, Henry Lee-Six, Laura Butlin, Nicola Lander, Rebekah Truscott, Mathijs A. Sanders, Stefanie Lensing, Simon J. A. Buczacki, Rogier Ten Hoopen, Nicholas Coleman, Roxanne Brunton-Sim, Simon Rushbrook, Kourosh Saeb-Parsy, Fiona Lalloo, Peter J. Campbell, Inigo Martincorena, Julian R. Sampson, Michael R. Stratton
Summary: Cellular DNA damage caused by reactive oxygen species is repaired by the base excision repair (BER) pathway which includes the DNA glycosylase MUTYH. Inherited biallelic MUTYH mutations cause predisposition to colorectal adenomas and carcinoma. The authors sequenced normal tissue DNAs from patients with MUTYH-Associated Polyposis (MAP) and found elevated somatic base substitution mutation rates in intestinal epithelial cells, leading to an increased cancer risk.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Eric Jou, Noe Rodriguez-Rodriguez, Ana-Carolina F. Ferreira, Helen E. Jolin, Paula A. Clark, Kovilen Sawmynaden, Michelle Ko, Jane E. Murphy, Jonathan Mannion, Christopher Ward, David J. Matthews, Simon J. A. Buczacki, Andrew N. J. McKenzie
Summary: Intestinal IL-25-activated ILC2s create a cancer-permissive microenvironment, associated with reduced survival and increased MDSCs in colorectal cancer patients. Ablation of IL-25 signaling reduces tumors and extends lifespan, while therapeutic antibody blockade enhances antitumor immunity.
SCIENCE IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Teresa Brevini, Mailis Maes, Gwilym J. Webb, Binu John, Claudia D. Fuchs, Gustav Buescher, Lu Wang, Chelsea Griffiths, Marnie L. Brown, William E. Scott, Pehuen Pereyra-Gerber, William T. H. Gelson, Stephanie Brown, Scott Dillon, Daniele Muraro, Jo Sharp, Megan Neary, Helen Box, Lee Tatham, James Stewart, Paul Curley, Henry Pertinez, Sally Forrest, Petra Mlcochova, Sagar S. Varankar, Mahnaz Darvish-Damavandi, Victoria L. Mulcahy, Rhoda E. Kuc, Thomas L. Williams, James A. Heslop, Davide Rossetti, Olivia C. Tysoe, Vasileios Galanakis, Marta Vila-Gonzalez, Thomas W. M. Crozier, Johannes Bargehr, Sanjay Sinha, Sara S. Upponi, Corrina Fear, Lisa Swift, Kourosh Saeb-Parsy, Susan E. Davies, Axel Wester, Hannes Hagstrom, Espen Melum, Darran Clements, Peter Humphreys, Jo Herriott, Edyta Kijak, Helen Cox, Chloe Bramwell, Anthony Valentijn, Christopher J. R. Illingworth, Bassam Dahman, Dustin R. Bastaich, Raphaella D. Ferreira, Thomas Marjot, Eleanor Barnes, Andrew M. Moon, Alfred S. Barritt, Ravindra K. Gupta, Stephen Baker, Anthony P. Davenport, Gareth Corbett, Vassilis G. Gorgoulis, Simon J. A. Buczacki, Joo-Hyeon Lee, Nicholas J. Matheson, Michael Trauner, Andrew J. Fisher, Paul Gibbs, Andrew J. Butler, Christopher J. E. Watson, George F. Mells, Gordon Dougan, Andrew Owen, Ansgar W. Lohse, Ludovic Vallier, Fotios Sampaziotis
Summary: Modulating the expression of angiotensin-converting enzyme 2 (ACE2) through farnesoid X receptor (FXR) can reduce susceptibility to SARS-CoV-2 infection, as shown in various tissues and organoids in vitro, in vivo, and ex vivo. The use of z-guggulsterone and ursodeoxycholic acid (UDCA) can downregulate ACE2 and decrease viral infection, including in the nasal epithelium. Clinical data also indicate positive outcomes with UDCA treatment in SARS-CoV-2 infection. These findings suggest that targeting the FXR-ACE2 pathway could be a potential strategy for preventing COVID-19.
Article
Genetics & Heredity
Yichen Wang, Philip S. Robinson, Tim H. H. Coorens, Luiza Moore, Henry Lee-Six, Ayesha Noorani, Mathijs A. Sanders, Hyunchul Jung, Riku Katainen, Robert Heuschkel, Roxanne Brunton-Sim, Robyn Weston, Debbie Read, Beverley Nobbs, Rebecca C. Fitzgerald, Kourosh Saeb-Parsy, Inigo Martincorena, Peter J. Campbell, Simon Rushbrook, Matthias Zilbauer, Simon James Alexander Buczacki, Michael R. Stratton
Summary: APOBEC mutational signatures SBS2 and SBS13 are commonly present in various human cancer types, but the stimulus, timing, and responsible APOBEC enzymes are not fully understood. Whole-genome sequencing of 342 microdissected normal epithelial crypts from the small intestines of 39 individuals revealed that SBS2/SBS13 mutations occurred in 17% of crypts, which is more frequent than in most other normal tissues. The study suggests that the high levels of SBS2/SBS13 in the small intestine are a result of APOBEC1 fulfilling its physiological function of editing APOB mRNA. Overall, APOBEC enzymes are a common contributor to the mutational burden in small intestine tissue.
Article
Biochemical Research Methods
Dedrick Kok Hong Chan, Scott David Collins, Simon James Alexander Buczacki
Summary: In this study, a multi-guide RNA CRISPR-Cas9 gene-editing protocol is described that enables efficient complete gene knockout in adult human colonic organoids. The protocol also details crucial steps for maximizing gene-editing efficacy through tissue harvesting and validating gene knockout using immunofluorescent staining of the organoids against the target protein.
Article
Gastroenterology & Hepatology
Dimitrios A. Koutoukidis, Susan A. Jebb, Claire Foster, Pete Wheatstone, Alison Horne, T. Martyn Hill, Amy Taylor, Alba Realpe, Felix Achana, Simon J. A. Buczacki
Summary: The aim of this trial is to assess the feasibility of intentional weight loss before colorectal cancer surgery and determine whether to proceed with a definitive trial.
COLORECTAL DISEASE
(2023)
Article
Cell Biology
Dedrick Kok Hong Chan, Amit Mandal, Svenja Hester, Zhanru Yu, Geoff Stuart Higgins, Benedikt Mathias Kessler, Roman Fischer, Simon James Alexander Buczacki
Summary: This study found that FBXW7 gene mutation in colorectal cancer cells leads to DNA damage in neighboring wildtype cells. The study also discovered that FBXW7 mutant cells induce DNA damage through the secretion of AKAP8 protein. These findings highlight the importance of understanding the local effects of cancer driver mutations between subclonal populations.
CELL DEATH DISCOVERY
(2023)
