Article
Biochemistry & Molecular Biology
Jianmin Hu, Jin Li, Can Dai, Jinlin Ren, Wenru Yang, Caixia He, Fei Meng, Congling Dai, Sicong Zeng
Summary: By introducing HES1-/-mutations into human embryonic stem cells and differentiating them into human intestinal organoids, the study reveals the important role of HES1 and WNT5A signaling in epithelial-mesenchymal crosstalk in the human intestinal mucosa.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Takenori Kotani, Noriko Ihara, Saki Okamoto, Jajar Setiawan, Tasuku Konno, Yasuyuki Saito, Yoji Murata, Takashi Matozaki
Summary: Cross talk between different signaling pathways is important for the regulation of intestinal homeostasis and tumorigenesis. Expression of active K-Ras in intestinal epithelial cells promotes proliferation and generation of goblet cells, while counter-regulating Wnt signaling for proper regulation of intestinal epithelial cell homeostasis.
Article
Gastroenterology & Hepatology
Katsutoshi Kuriyama, Yuzo Kodama, Masahiro Shiokawa, Yoshihiro Nishikawa, Saiko Marui, Takeshi Kuwada, Yuko Sogabe, Nobuyuki Kakiuchi, Teruko Tomono, Tomoaki Matsumori, Atsushi Mima, Toshihiro Morita, Tatsuki Ueda, Motoyuki Tsuda, Yuki Yamauchi, Yojiro Sakuma, Yuji Ota, Takahisa Maruno, Norimitsu Uza, Ryoichiro Kageyama, Tsutomu Chiba, Hiroshi Seno
Summary: Notch/Hes1 signaling is essential for the postnatal maturation of exocrine tissue in pancreatic progenitor cells, partially through the formation of centroacinar cells.
JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Cell & Tissue Engineering
Rachel E. Niec, Tinyi Chu, Marina Schernthanner, Shiri Gur-Cohen, Lynette Hidalgo, Hilda Amalia Pasolli, Kathleen A. Luckett, Zhong Wang, Sohni R. Bhalla, Francesco Cambuli, Raghu P. Kataru, Karuna Ganesh, Babak J. Mehrara, Dana Pe'er, Elaine Fuchs
Summary: This study reveals a lymphatic network associated with intestinal stem cells (ISCs) in the small and large intestines. The crypt lymphatics maintain ISCs and prevent their premature differentiation. Using single-cell and spatial transcriptomics, lymphatics are identified as a central signaling hub for the crypt and ISCs.
Review
Biochemistry & Molecular Biology
Joep Sprangers, Irene C. Zaalberg, Madelon M. Maurice
Summary: This review discusses the regenerative response of intestinal epithelial cells to injury, as well as how the Wnt and YAP signaling pathways control intestinal repair. It also emphasizes how organoid-based applications have contributed to unraveling the key mechanisms behind these developmental and regenerative events.
CELL DEATH AND DIFFERENTIATION
(2021)
Review
Biochemistry & Molecular Biology
Ken Kurokawa, Yoku Hayakawa, Kazuhiko Koike
Summary: The discovery of Lgr5+ intestinal stem cells has revolutionized ISC research, revealing their crucial role in maintaining intestinal epithelium homeostasis and regeneration. Regulatory mechanisms in the stem cell niche and the role of inflammatory cytokines in epithelial regeneration are key areas of current understanding in ISC research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Liu Yang, Haiyan Yang, Yunxiang Chu, Yunhao Song, Lidan Ding, Bingtao Zhu, Wanli Zhai, Xuning Wang, Yanshen Kuang, Fangli Ren, Baoqing Jia, Wei Wu, Xiongjun Ye, Yinyin Wang, Zhijie Chang
Summary: This study reveals the essential role of CREPT in maintaining murine intestinal stem cells, with its deficiency impairing cell proliferation and regeneration. The downregulation of Wnt signaling due to CREPT deletion is identified as a key mechanism affecting ISC function.
NATURE COMMUNICATIONS
(2021)
Article
Gastroenterology & Hepatology
Saiko Marui, Yoshihiro Nishikawa, Masahiro Shiokawa, Masataka Yokode, Shimpei Matsumoto, Yuya Muramoto, Sakiko Ota, Takeharu Nakamura, Hiroyuki Yoshida, Hirokazu Okada, Takeshi Kuwada, Tomoaki Matsumori, Katsutoshi Kuriyama, Akihisa Fukuda, Dieter Saur, Takashi Aoi, Norimitsu Uza, Yuzo Kodama, Tsutomu Chiba, Hiroshi Seno
Summary: The roles of HES1 in the adult pancreas and pancreatic cancer are context-dependent. HES1 is not required for maintaining the adult pancreas under normal conditions, but is important for regeneration during recovery from pancreatitis. Furthermore, HES1 promotes early lesion formation while inhibiting the progression of late lesions in pancreatic cancer.
Article
Multidisciplinary Sciences
Ohman Kwon, Kwang Bo Jung, Kyeong-Ryoon Lee, Ye Seul Son, Hana Lee, Jong-Jin Kim, Kwangho Kim, Seop Lee, Yoo-Kyung Song, Jaeeun Jung, Kunhyang Park, Dae-Soo Kim, Myung Jin Son, Mi-Ok Lee, Tae-Su Han, Hyun-Soo Cho, Soo Jin Oh, Haeun Chung, Sang-Heon Kim, Kyung-Sook Chung, Janghwan Kim, Cho-Rok Jung, Mi-Young Son
Summary: A reproducible two-step protocol was developed to induce human pluripotent stem cells into highly expandable hIEC progenitors and functional hIEC monolayers. This system is more suitable for predicting CYP3A4 metabolism and intestinal absorption than traditional Caco-2 cells.
Article
Biology
Ali Hageb, Torsten Thalheim, Kalpana J. Nattamai, Bettina Moehrle, Mehmet Sacma, Vadim Sakk, Lars Thielecke, Kerstin Cornils, Carolin Grandy, Fabian Port, Kay-E Gottschalk, Jan-Philipp Mallm, Ingmar Glauche, Joerg Galle, Medhanie A. Mulaw, Hartmut Geiger
Summary: The function of the intestinal epithelium declines with aging, leading to an increase in aging-related diseases. Intestinal stem cells (ISCs) play a crucial role in this process. The clonal dynamics of ISCs follow a neutral drift model, but it is unclear if this model still applies to aged ISCs. Clonal tracing experiments revealed that aged crypts drift into monoclonality faster than young ones, but in vivo and ex vivo ISC tracing experiments showed similar clonal expansion abilities in both young and aged ISCs. Single-cell RNA sequencing of ISCs from young and aged mice revealed increased heterogeneity among subgroups of aged ISCs, with down-regulation of genes associated with cell adhesion. Simulations indicated that reduced adhesion strength accelerates clonal drift in the small intestinal crypt, suggesting a central role of reduced adhesion in affecting clonal dynamics during aging.
LIFE SCIENCE ALLIANCE
(2022)
Article
Biophysics
A. A. Almet, H. M. Byrne, P. K. Maini, D. E. Moulton
Summary: The study introduces a mechanical model specialized to the intestinal crypt for tissue homeostasis, using morphoelastic rod theory to model growth and deformation of the crypt. By analyzing mechanochemical growth mechanisms and identifying necessary conditions for homeostasis, essential features of crypt homeostasis are extracted, alongside deriving closed-form solutions for growth and sloughing dynamics in homeostasis. The importance of crypt morphology on homeostatic growth, migration, and sloughing is demonstrated through numerical solutions, highlighting the value of this framework for studying the role of mechanics in homeostasis.
BIOMECHANICS AND MODELING IN MECHANOBIOLOGY
(2021)
Review
Microbiology
Yeboah Kwaku Opoku, Kwame Kumi Asare, George Ghartey-Quansah, Justice Afrifa, Felicity Bentsi-Enchill, Eric Gyamerah Ofori, Charles Kwesi Koomson, Rosemary Kumi-Manu
Summary: Rheumatoid arthritis is a globally significant autoimmune disease. Alterations in the gut microbiome are associated with the development and progression of rheumatoid arthritis, and probiotics show promise as an adjuvant therapy for its management.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Environmental Sciences
Min Zhu, Rongguo Wei, Yuanyuan Li, Jinbo Li, Mengqi Dong, Xuanyue Chen, Lin Lv, Zhanfen Qin
Summary: Emerging evidence suggests that bisphenol A (BPA) can negatively affect the intestinal barrier in rodents, and this study aimed to explore the mechanisms underlying this. The researchers found that BPA and its substitute bisphenol F (BPF) disrupted Notch signaling and altered intestinal histological structures in tadpoles. When administered to adult mice at reference doses, BPA and BPF downregulated the expression of Notch- and Wnt-related genes and disrupted intestinal homeostasis. Additionally, extended exposure to both substances suppressed the expression of tested genes, reduced cell proliferation, and led to mucosal barrier dysregulation and intestinal inflammation. This study is the first to demonstrate the adverse effects of BPF on mammalian intestines and uncover the underlying mechanisms for bisphenol-induced intestinal injury.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Cell Biology
Laura E. Sanman, Ina W. Chen, Jake M. Bieber, Veronica Steri, Coralie Trentesaux, Byron Hann, Ophir D. Klein, Lani F. Wu, Steven J. Altschuler
Summary: By investigating the responses of intestinal epithelium to different signaling pathways, it was found that modulation of transit-amplifying cell proliferation can change the ratio of differentiated cell types, highlighting the important role of transit-amplifying cells in tuning differentiated cell-type composition.
DEVELOPMENTAL CELL
(2021)
Review
Oncology
Rana Ramadan, Milou S. van Driel, Louis Vermeulen, Sanne M. van Neerven
Summary: The relationship between intestinal stem cells and colorectal cancer has been intensively studied, uncovering the dynamics of stem cells in homeostasis and cancer initiation. The microenvironment plays a crucial role in regulating stem cell fate and functionality, and imbalances in signaling between the niche and stem cells can disturb homeostasis and promote cancer development.
Article
Mathematics, Applied
Meraj Alam, H. M. Byrne, G. P. Raja Sekhar
Summary: This article introduces a mathematical model for describing hydrodynamics and deformation mechanics in solid tumors embedded or adjacent to healthy tissues. The model accounts for the deformability of tumor and normal tissue regions, as well as the nonlinearity caused by heterogeneous and deformation-dependent physiological transport parameters. The study establishes the existence of a unique weak solution and its continuity with respect to the given data using Galerkin and weak convergence methods.
APPLICABLE ANALYSIS
(2022)
Article
Biology
Blake Cook, Alex Combes, Melissa Little, James M. Osborne
Summary: Kidney diseases and disorders are common in mid-late adulthood worldwide, often caused by improper formation of the kidneys before birth. Researchers have used mathematical modeling to study kidney development and investigated the behavior of cap mesenchyme cells and their impact on kidney growth. The study found that spatial regulation of cell differentiation and increased cell adhesion can ensure healthy kidney development.
BULLETIN OF MATHEMATICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rebecca Williams, Stephanie Jobling, Andrew H. Sims, Chunyan Mou, Lorna Wilkinson, Giovanna M. Collu, Charles H. Streuli, Andrew P. Gilmore, Denis J. Headon, Keith Brennan
Summary: This study highlights the significance of EDAR in ER-negative breast carcinomas and its correlation with tumorigenesis in mice. Elevated EDAR signaling leads to mammary tumors with squamous differentiation and increased beta-catenin activity, suggesting a novel mechanism of transformation based on interaction between the WNT and EDA pathways.
Article
Biochemistry & Molecular Biology
Louise E. King, Ricardo Rodriguez-Enriquez, Robert Pedley, Charlotte E. L. Mellor, Pengbo Wang, Egor Zindy, Michael R. H. White, Keith Brennan, Andrew P. Gilmore
Summary: Mitochondrial priming, an important process in regulating cell apoptosis, is closely related to the retrotranslocation dynamics of Bcl-XL. This study reveals that the binding of Bcl-XL to its BH3-only partners inhibits its retrotranslocation, leading to accumulation of protein complexes carrying priming on mitochondria. Additionally, heterogeneity in priming between cells within a population is found, which predicts their subsequent response to pro-apoptotic signals.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biology
Gopikrishnan C. C. Remesan, Jennifer A. A. Flegg, Helen M. M. Byrne
Summary: In vitro experiments demonstrate the impact of mechanical interactions between tumour cells and the surrounding tissue in a gelatinous medium, as well as the local levels of diffusible nutrients, on tumour growth dynamics. A mathematical model is presented to describe these experiments, revealing the influence of mechanical deformations in the hydrogel on tumour growth. Variations in the hydrogel's mechanical properties affect the tumour's equilibrium size, with soft hydrogels favoring nutrient availability and larger tumour size, while stiff hydrogels can eliminate tumours due to increased mechanical resistance. The model analysis identifies parameter regimes in which the hydrogel contributes to tumour elimination.
JOURNAL OF MATHEMATICAL BIOLOGY
(2023)
Article
Biology
Heyrim Cho, Allison L. Lewis, Kathleen M. Storey, Helen M. Byrne
Summary: This article investigates the inference of interaction types between two tumor cell lines using the Lotka-Volterra model. Three experimental designs are evaluated for identifiability and predictive power of the model. The study also highlights the need for caution when interpreting parameter estimates for the spatially-averaged Lotka-Volterra model calibrated against data from a spatially-resolved cellular automaton model.
JOURNAL OF THEORETICAL BIOLOGY
(2023)
Article
Biology
Giulia L. Celora, Helen M. Byrne, P. G. Kevrekidis
Summary: This study presents a mathematical model that describes the evolution of tumour heterogeneity in a tissue slice oxygenated by a single blood vessel. The model considers the phenotype of tumour cells, which determines their proliferative capacity, apoptosis propensity, and response to treatment. Numerical simulations reveal the multiple steady states of the system and the role of tissue oxygen levels in the efficacy of radiation protocols commonly used in the clinic.
JOURNAL OF THEORETICAL BIOLOGY
(2023)
Article
Biology
Richard Creswell, Martin Robinson, David Gavaghan, Kris Parag, Chon Lok Lei, Ben Lambert
Summary: This article presents a method called EpiCluster for estimating changes in the reproduction number, Rt, of infectious diseases. The method is based on Bayesian nonparametric modeling and can automatically detect rapid changes in transmission rate and provide measures of uncertainty. It has wide applications in epidemiology.
JOURNAL OF THEORETICAL BIOLOGY
(2023)
Article
Biology
Rahil Sachak-Patwa, Erin I. Lafferty, Claude J. Schmit, Robin N. Thompson, Helen M. Byrne
Summary: This article studies a hierarchy of ordinary differential equation models that describe the within-host viral kinetics of influenza infections, where the IR model explicitly accounts for an immune response to the virus, while the simpler TEIV and TV models do not. It is shown that the parameters values of the IR model can be determined when fitting it to experimental murine data considering the viral load, fraction of dead cells, and immune response levels. However, if only viral load data are available, we can estimate parameters of the TEIV and TV models but not the IR model. These results are supported by a structural and practical identifiability analysis. The study concludes that a simple target-cell limited model, such as the TV model, can reproduce influenza infection dynamics and distinguish between hosts with differing immune responses, if only viral load data are available.
JOURNAL OF THEORETICAL BIOLOGY
(2023)
Article
Biology
Keith L. Chambers, Mary R. Myerscough, Helen M. Byrne
Summary: Athersclerotic plaques are formed by lipid accumulation in artery walls, driven by chronic inflammatory response. The impact of blood LDL/HDL levels on plaque composition and lipid distribution in plaque macrophages remains unexplored. In this study, we develop a lipid-structured mathematical model to investigate this impact and find that plaque lipid content is sensitive to the influx of LDL relative to HDL capacity. The macrophage lipid distribution evolves in a wave-like manner towards an equilibrium profile, and lipid accumulation may severely impair macrophage uptake.
MATHEMATICAL BIOSCIENCES
(2023)
Article
Biology
Domenic P. J. Germano, Adriana Zanca, Stuart T. Johnston, Jennifer A. Flegg, James M. Osborne
Summary: Coordination of cell behavior is crucial for various biological processes. Individual-based computational models are commonly used to simulate collective cell dynamics, but the impact of cell boundary descriptions on overall population dynamics is unclear. This study explores different cell boundary descriptions in commonly used individual-based models and investigates their influence on tissue-scale behavior in various biological scenarios.
BULLETIN OF MATHEMATICAL BIOLOGY
(2023)
Article
Biology
Thomas Williams, James M. McCaw, James M. Osborne
Summary: This study investigates the impact of spatial discretization on the behavior of models of viral spread within tissues. The results show that the choice of discretization method can qualitatively change key outcomes, including the time scale of infection. Additionally, implementing viral spread as a cell-scale process or as a high-resolution converged PDE can result in distinct model outcomes, raising important conceptual questions about the assumptions underlying the spatial structure of the model.
JOURNAL OF THEORETICAL BIOLOGY
(2023)
Article
Medicine, Research & Experimental
Daria Stepanova, Helen M. Byrne, Philip K. Maini, Tomas Alarcon
Summary: Angiogenesis is a complex biological process involving the formation of new blood vessels by endothelial cells. Theoretical modeling has contributed to our understanding of this process, but current models based on the snail-trail hypothesis may not fully capture the role of cell mixing. This review focuses on the phenomenon of cell mixing during angiogenic sprouting and discusses its functional role in theoretical models.
WIRES MECHANISMS OF DISEASE
(2023)
Review
Medicine, Research & Experimental
Aditi Agrawal, Ken Wang, Liudmila Polonchuk, Jonathan Cooper, Maurice Hendrix, David J. Gavaghan, Gary R. Mirams, Michael Clerx
Summary: The L-type calcium current (ICaL) plays a critical role in cardiac electrophysiology. However, there is a large variability in the predictions of different ICaL models, and it is unclear which model is best suited for specific applications. Further experimental and modeling work is needed to reduce the competing theories and develop a consensus ICaL model.
WIRES MECHANISMS OF DISEASE
(2023)
Article
Medicine, Research & Experimental
Alexander G. Fletcher, James M. Osborne
Summary: The growth and dynamics of multicellular tissues involve complex cellular behaviors at multiple scales, and computational modeling approaches are crucial for understanding these processes. However, such models face technical and computational challenges.
WIRES MECHANISMS OF DISEASE
(2022)