Article
Developmental Biology
Yukino Wada, Hikaru Tsukatani, Chihiro Kuroda, Yurika Miyazaki, Miku Otoshi, Isao Kobayashi
Summary: This study identifies a previously unknown spatiotemporal regulatory mechanism of hematopoietic stem cell specification by somites in zebrafish, in which Jag2b-induced Notch signaling leads to the expression of wnt16 and HSC markers.
Article
Biochemistry & Molecular Biology
Maximilian McCann, Yueru Li, Basma Baccouche, Andrius Kazlauskas
Summary: The goal of this study was to identify genes involved in VEGF-induced permeability. RNA-Seq analysis was performed on primary human retinal endothelial cells treated with VEGF or VEGF plus anti-VEGF under normal and high glucose conditions. Genes that met specific criteria related to VEGF regulation and vascular homeostasis were identified, including members of the Notch signaling pathway and ANGPT2. The findings indicate that VEGF activates different sets of genes to induce and sustain barrier relaxation, with Notch pathway contributing to maintaining an open barrier and Ang2 limiting the extent of barrier relaxation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Developmental Biology
Sriivatsan G. Rajan, Lynne M. Nacke, Jagjot S. Dhingra, Ankur Saxena
Summary: This study in zebrafish identified the earliest time window of olfactory MCC differentiation, showing that OMCC cells derive from peridermal cells and are regulated by the Notch signaling pathway. The research also found regionally segregated Notch signaling regulates the number of OMCCs and the differentiation-associated genes during olfactory development.
CELLS & DEVELOPMENT
(2021)
Article
Physiology
Eszter K. Vladar, Koshi Kunimoto, Laura S. Rojas-Hernandez, Jacquelyn M. Spano, Zachary M. Sellers, Nam Soo Joo, Riley A. Cooney, Jeffrey D. Axelrod, Carlos E. Milla
Summary: Loss of multiciliated cells is a common characteristic in chronic inflammatory airway diseases. Notch signaling plays a crucial role in controlling the proportion of multiciliated and secretory cells. Inhibition of Notch activation using a small molecule inhibitor can promote differentiation towards the multiciliated lineage. LY450139, a specific ?-secretase inhibitor, has shown potential in increasing multiciliated cell numbers without toxicity in both healthy and diseased lung cells, suggesting it as a promising therapeutic option to restore multiciliated cells and improve epithelial function in chronic lung diseases.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2023)
Article
Cell Biology
Yu Zhang, Moises Hernandez, Jonathan Gower, Nolan Winicki, Xena Morataya, Sebastian Alvarez, Jason X-J Yuan, John Shyy, Patricia A. Thistlethwaite
Summary: This study found that the NOTCH3 pathway plays a crucial role in controlling vascular smooth muscle cell proliferation and differentiation in the pulmonary arterial tree. In pulmonary arterial hypertension (PAH) patients, JAGGED-1 is overexpressed in small pulmonary artery smooth muscle cells and selectively activates NOTCH3 signaling, leading to increased cellular proliferation. On the other hand, DELTA-LIKE 4 inhibits NOTCH3 signaling and retards smooth muscle cell proliferation. A new monoclonal antibody was developed to block JAGGED-1-induced cleavage of NOTCH3 and successfully reversed pulmonary hypertension in animal models without toxic side effects. Targeting JAGGED-1 activation of NOTCH3 may be an effective and safe strategy for treating PAH.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Engineering, Biomedical
Muhammad Rizwan, Christopher Ling, Chengyu Guo, Tracy Liu, Jia-Xin Jiang, Christine E. Bear, Shinichiro Ogawa, Molly S. Shoichet
Summary: A defined viscoelastic hyaluronan hydrogel is designed to mimic the stress relaxation rate of liver tissue, promoting cholangiocyte organoid growth. Hydrogel viscoelasticity, YAP signaling, and Notch activation play critical roles in cholangiocyte organogenesis.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Oncology
Fengjiao Wang, Lai Wang, Chao Qu, Lianyu Chen, Yawen Geng, Chienshan Cheng, Shulin Yu, Dan Wang, Lina Yang, Zhiqiang Meng, Zhen Chen
Summary: Kaempferol effectively suppresses pancreatic cancer by upregulating ROS levels and inducing apoptosis via TGM2-mediated Akt/mTOR signaling pathway. High TGM2 expression is correlated with poor prognosis in pancreatic cancer patients, and TGM2 may serve as a promising prognostic biomarker for pancreatic cancer.
Article
Biochemistry & Molecular Biology
Stefania Zorzin, Andrea Corsi, Francesca Ciarpella, Emanuela Bottani, Sissi Dolci, Giorgio Malpeli, Annachiara Pino, Alessia Amenta, Guido Franceso Fumagalli, Cristiano Chiamulera, Francesco Bifari, Ilaria Decimo
Summary: The study revealed that environmental enrichment (EE) stimulus can modulate neural precursor cell distribution in meninges through BDNF-TrkB signaling, highlighting the importance of environmental stimuli on brain regeneration. The findings suggest that the meningeal niche could respond to pharmacological neurogenic stimuli, potentially offering new avenues for enhancing treatments for neurodegenerative and neuropsychiatric disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Rongxiang Huang, Zhang Hui, Sun Wei, Duan Li, Wencui Li, Wang Daping, Murad Alahdal
Summary: IRE1 plays a crucial role in regulating the unfolded protein response in the endoplasmic reticulum, affecting cell fate through endonuclease activation. Different levels of IRE1α can impact chondrocyte survival and apoptosis.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Cell Biology
Nathalie Boulet, Anais Briot, Valentin Jargaud, David Esteve, Anne Remaury, Chloe Belles, Penelope Viana, Jessica Fontaine, Lucie Murphy, Catherine Deon, Marie Guillemot, Catherine Pech, Yaligara Veeranagouda, Michel Didier, Pauline Decaunes, Etienne Mouisel, Christian Carpene, Jason S. Iacovoni, Alexia Zakaroff-Girard, Jean-Louis Grolleau, Jean Galitzky, Severine Ledoux, Jean-Claude Guillemot, Anne Bouloumie
Summary: Senescence is a critical event in the dysfunction of adipose tissue (AT) due to obesity and aging, but the molecular and cellular factors underlying this process in human AT progenitors are not yet fully understood. Researchers have identified distinct profiles of senescent progenitors based on their location within AT, specifically visceral and subcutaneous AT. In addition to flow cytometry, the study used transcriptomic and proteomic approaches to uncover the genes and developmental pathways involved in replicative senescence, including INBHA, SFRP4, GREM1, and NOTCH3. Activation of NOTCH3 in AT progenitors inhibits adipogenesis and promotes myofibrogenesis, contributing to AT dysfunction in obesity and aging.
Article
Cell Biology
Wenjie Ge, Yudong Wang, Shanliang Zheng, Dong Zhao, Xingwen Wang, Xiaoshi Zhang, Ying Hu
Summary: The study reveals that iASPP can inhibit apoptosis when p53 is activated, but may promote apoptosis when NF-kappa Bp65 is activated. iASPP preferentially inhibits the transcriptional activity of p53 over NF-kappa Bp65, resulting in an antiapoptotic outcome when both TFs are simultaneously activated.
CELL DEATH DISCOVERY
(2021)
Article
Immunology
Paola Grazioli, Andrea Orlando, Nike Giordano, Claudia Noce, Giovanna Peruzzi, Behnaz Abdollahzadeh, Isabella Screpanti, Antonio Francesco Campese
Summary: This study reveals that dysregulation of the Notch signaling pathway in T cells promotes the production of MDSCs in a T-ALL mouse model. IL-6 is found to mediate the induction of MDSCs in both mouse and human models.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Jin Li, Ane M. Salvador, Guoping Li, Nedyalka Valkov, Olivia Ziegler, Ashish Yeri, Chun Yang Xiao, Bessie Meechoovet, Eric Alsop, Rodosthenis S. Rodosthenous, Piyusha Kundu, Tianxiao Huan, Daniel Levy, John Tigges, Alexander R. Pico, Ionita Ghiran, Michael G. Silverman, Xiangmin Meng, Robert Kitchen, Jiahong Xu, Kendall Van Keuren-Jensen, Ravi Shah, Junjie Xiao, Saumya Das
Summary: miR-30d can improve cardiac function and reduce fibrosis by targeting MAP4K4 and integrin alpha 5, showing a protective effect in ischemic heart failure. The communication of extracellular vesicle-contained miRNAs may provide a novel therapeutic target in heart failure treatment.
CIRCULATION RESEARCH
(2021)
Article
Genetics & Heredity
Andriy S. Yatsenko, Halyna R. Shcherbata
Summary: This study reveals that multiple modes of Notch signaling activation contribute to the specification of spatial cellular interactions necessary for stem cell niche assembly in Drosophila. It demonstrates the trans-activation of Notch signaling among non-equipotent cells through distant induction, as well as a secondary security mechanism controlled by the soma to ensure the formation of the stem cell niche. These findings advance our understanding of Notch signaling and stem cell niche formation, with implications for stem cell biology and regenerative medicine.
Article
Biochemistry & Molecular Biology
Hongling Huang, Peipei Zhou, Jun Wei, Lingyun Long, Hao Shi, Yogesh Dhungana, Nicole M. Chapman, Guotong Fu, Jordy Saravia, Jana L. Raynor, Shaofeng Liu, Gustavo Palacios, Yong-Dong Wang, Chenxi Qian, Jiyang Yu, Hongbo Chi
Summary: This study reveals that amino acid transporters play a role in dampening T-MEM differentiation, while Pofut1 is a key regulator for terminal effector differentiation of T-EFF cells. These findings highlight the importance of nutrient uptake and signaling in determining T cell fate.
Article
Cell Biology
Maximilian Haas, Jose Luis Gomez Vazquez, Dingyuan Iris Sun, Hong Thi Tran, Magdalena Brislinger, Alexia Tasca, Orr Shomroni, Kris Vleminckx, Peter Walentek
Article
Cell Biology
Huaize Liu, Jie Ding, Karl Koehnlein, Nadine Urban, Alessandro Ori, Pablo Villavicencio-Lorini, Peter Walentek, Lars-Oliver Klotz, Thomas Hollemann, Thorsten Pfirrmann
Review
Developmental Biology
Peter Walentek
Summary: The Xenopus embryonic epidermis serves as a powerful model for studying mucociliary biology, development, and disease, offering significant insights into potential molecular mechanisms. It has also been utilized for research on epithelial remodeling and cell differentiation.
Review
Anatomy & Morphology
Peter Walentek
Summary: Mucociliary epithelia play a crucial role in protecting organs such as the respiratory tract against inhaled particles and pathogens. Understanding the mechanisms of cell type composition and maintenance in these epithelia is important for the treatment of various diseases. Studies have revealed important signaling control mechanisms in mucociliary cell types, highlighting the plasticity of cell identity. This review summarizes major findings and provides perspectives for future research and treatment of chronic airway diseases associated with tissue remodeling.
CELLS TISSUES ORGANS
(2023)
Article
Multidisciplinary Sciences
Anja Beckers, Franziska Fuhl, Tim Ott, Karsten Boldt, Magdalena Maria Brislinger, Peter Walentek, Karin Schuster-Gossler, Jan Hegermann, Leonie Alten, Elisabeth Kremmer, Adina Przykopanski, Katrin Serth, Marius Ueffing, Martin Blum, Achim Gossler
Summary: The FOXJ1 target CFAP161 is evolutionarily conserved in Xenopus and mouse, where its expression correlates with motile cilia presence but mutations do not lead to typical cilia-related phenotypes. Genetic compensation and dysregulation of genes related to microtubules and cilia may buffer the impact of Cfap161 mutation.
SCIENTIFIC REPORTS
(2021)
Article
Physiology
Carolin A. Boecking, Peter Walentek, Lorna T. Zlock, Dingyuan Sun, Paul J. Wolters, Hiroaki Ishikawa, Byung-Ju Jin, Peter M. Haggie, Wallace F. Marshall, Alan S. Verkman, Walter E. Finkbeiner
Summary: The method described in this study allows for the generation of differentiated tracheobronchospheres without pretreatments, providing a model to study cilia formation and function, disease pathogenesis, and interaction of pathogens with the respiratory mucosa. This culture system may be useful for studying airway biology and pathophysiology, aiding diagnosis of ciliopathies, and potentially for high-throughput drug screening.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2022)
Article
Cell Biology
Friederike Hantel, Huaize Liu, Lisa Fechtner, Herbert Neuhaus, Jie Ding, Danilo Arlt, Peter Walentek, Pablo Villavicencio-Lorini, Christoph Gerhardt, Thomas Hollemann, Thorsten Pfirrmann
Summary: Cilia play an important role in embryonic development, and the GID complex is involved in primary cilia-dependent signal transduction and protein homeostasis. GID subunits may be candidate genes for human ciliopathies associated with defects in Hedgehog signaling.
JOURNAL OF CELL SCIENCE
(2022)
Article
Multidisciplinary Sciences
Takayuki Yasunaga, Johannes Wiegel, Max D. Bergen, Martin Helmstaedter, Daniel Epting, Andrea Paolini, Oezgun Cicek, Gerald Radziwill, Christina Engel, Thomas Brox, Olaf Ronneberger, Peter Walentek, Maximilian H. Ulbrich, Gerd Walz
Summary: Motile cilia of Xenopus epidermis are anchored to microridge-like membrane protrusions to maintain their directionality. The actin cytoskeleton is dynamic during the early development of multiciliated cells, and subapical actin filaments are anchored to microridge-like structures. These observations identify microridge-like structures as an essential component of basal body rootlet anchoring in MCCs.
NATURE COMMUNICATIONS
(2022)
Article
Developmental Biology
Rosa Ventrella, Sun K. Kim, Jennifer Sheridan, Aline Grata, Enzo Bresteau, Osama A. Hassan, Eve E. Suva, Peter Walentek, Brian J. Mitchell
Summary: Xenopus embryos undergo significant epithelial remodeling during development, including the complete loss of multiciliated cells (MCCs). This study describes two distinct mechanisms, basal extrusion driven by Notch signaling and apical extrusion driven by Piezo1, for MCC extrusion. The response to these signals is age-dependent and the maintenance of the MCC transcriptional program plays a crucial role in cell loss prevention.
Review
Biochemistry & Molecular Biology
Jay Gopalakrishnan, Kerstin Feistel, Benjamin M. Friedrich, Anne Grapin-Botton, Nathalie Jurisch-Yaksi, Elvira Mass, David U. Mick, Roman-Ulrich Mueller, Helen May-Simera, Bernhard Schermer, Miriam Schmidts, Peter Walentek, Dagmar Wachten
Summary: Primary cilia are dynamic cellular protrusions that play a crucial role in sensing and processing extracellular signals, controlling cell fate, and function during tissue development.