Article
Developmental Biology
Adam Packard, William H. Klein, Frank Costantini
Summary: Research has shown that Ret signaling in kidney development is crucial for maintaining tip cells in the ureteric bud. Cells genetically forced to maintain Ret expression exhibit a tip-seeking behavior and self-organize into dense clusters in organoids. This suggests that Ret-dependent cell behaviors play a significant role in normal branching morphogenesis.
Article
Biochemistry & Molecular Biology
Liping Chen, Shihao Zhu, Tianyuan Liu, Xuan Zhao, Tao Xiang, Xiao Hu, Chen Wu, Dongxin Lin
Summary: This study unravels the role of EFNB1-EPHB4 interaction in triggering epithelial-mesenchymal transition (EMT) and cell proliferation in epithelial cancer formation and progression.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Immunology
Claudia Haftmann, Pascale Zwicky, Florian Ingelfinger, Florian Mair, Stefan Floess, Rene Riedel, Pawel Durek, Marianne R. Spalinger, Ekaterina Friebel, Brian P. Leung, Mirjam Lutz, Nicole Puertas, Ana Amorim, Stefanie Scharli, Benedict Becher, Jan Kisielow, Ari Waisman, Mir-Farzin Mashreghi, Jochen Huehn, Burkhard Becher
Summary: Medullary thymic epithelial cells (mTECs) play a crucial role in regulating T cell immune tolerance by negatively selecting self-reactive T cells and promoting the development of regulatory T cells. Dysfunctional regulatory T cells may be a key factor in the development of autoimmune diseases.
SCIENCE IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Javier Garcia-Ceca, Sara Montero-Herradon, Ana Gonzalez, Rosa Plaza, Agustin G. Zapata
Summary: The lack of EphA4 alters T-cell differentiation and the histological organization of the thymus, impacting various T cell subsets as well as the proportions of thymocytes selected positively and negatively.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Cell Biology
Sinead Kinsella, Cindy A. Evandy, Kirsten Cooper, Lorenzo Iovino, Paul C. DeRoos, Kayla S. Hopwo, David W. Granadier, Colton W. Smith, Shahin Rafii, Jarrod A. Dudakov
Summary: The study identifies a complex signal pathway triggered by apoptotic thymocytes during tissue damage, leading to increased production of IL-23 and BMP4 and ultimately promoting thymic regeneration. Pharmacological inhibition targeting this pathway enhances thymic function and offers a new strategy for restoring immune competence in patients with compromised thymic function.
Article
Immunology
Jiayi Dong, Lindsey M. Warner, Ling-Li Lin, Mei-Chi Chen, Ryan M. O'Connell, Li-Fan Lu
Summary: miR-155 plays a crucial role in promoting tT reg cell differentiation by promoting mTEC maturation in the thymus. RANKL stimulation induces miR-155 expression to target molecules within the TGF beta signaling pathway, safeguarding thymic medulla integrity.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Reema Jain, Kelin Zhao, Julie M. Sheridan, Melanie Heinlein, Fiona Kupresanin, Waruni Abeysekera, Cathrine Hall, James Rickard, Philippe Bouillet, Henning Walczak, Andreas Strasser, John Silke, Daniel H. D. Gray
Summary: The study reveals the crucial role of the linear ubiquitin chain assembly complex in thymic epithelial cell differentiation and survival, with deficiency in LUBAC proteins severely impacting thymic tissue expansion and cell survival, potentially leading to premature thymic atrophy.
CELL DEATH AND DIFFERENTIATION
(2021)
Review
Immunology
Manpreet K. Semwal, Nicholas E. Jones, Ann V. Griffith
Summary: The thymus is crucial for T lymphocyte development, with thymic stromal cells playing an important role. Metabolic regulation of thymic stromal cell function is an emerging area of study.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Sandra Bajana, Aneta Pankow, Kaili Liu, Martyna Michniowska, Joseph F. Urban, Wei R. Chen, Xiao-Hong Sun
Summary: The thymus plays a role in maintaining the homeostasis of ILC pools in tissues, especially in the absence of E protein transcription factors. ILC precursors can differentiate into various subsets in vitro, and in steady state, icCD3 epsilon(+) cells differentiate into diverse ILC subsets in different tissue environments. Helminth infection promotes their differentiation into functional ILC2s. This finding may help explain age-related differences in immune responses, as thymic activity is age-dependent.
Review
Immunology
Takeshi Nitta, Hiroshi Takayanagi
Summary: The stromal microenvironment in the thymus is crucial for generating a functional T cell repertoire, with thymic epithelial cells (TECs) being the most prominent type. Besides TECs, other stromal cell types of mesenchymal origin also play important roles in controlling TEC development. The recently discovered functional effect of thymic fibroblasts on T cell repertoire selection is highlighted as a significant advancement in our understanding of thymic organogenesis and T cell development.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Thomas Barthlott, Adam E. Handel, Hong Ying Teh, Rushika C. Wirasinha, Katrin Hafen, Saulius Zuklys, Benoit Roch, Stuart H. Orkin, Jean-Pierre de Villartay, Stephen R. Daley, Georg A. Hollaender
Summary: Thymic T cell development and T cell receptor repertoire selection rely on molecular signals from thymic epithelial cells (TEC), whose development and function are epigenetically regulated. Disruption of PRC2 activity alters H3K27me3 configuration, impairs TEC functions, and affects T cell development.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Tadashi Sakane, Yuma Sakamoto, Ayako Masaki, Takayuki Murase, Katsuhiro Okuda, Ryoichi Nakanishi, Hiroshi Inagaki
Summary: The mutational profile of thymic carcinoma, including squamous cell carcinomas, was analyzed using next-generation sequencing. TP53, KIT, and PDGFRA were the most frequently mutated genes. Squamous cell carcinomas with mutations in receptor tyrosine kinases had significantly shorter survival time.
CLINICAL LUNG CANCER
(2021)
Article
Cell Biology
Weihong Gu, Darling Melany C. Madrid, Sebastian Joyce, John P. Driver
Summary: In this study, single-cell RNA sequencing was used to create a cell atlas of the early-adolescent pig thymus, revealing conserved features and species-specific differences compared to human thymocytes. The study also identified unconventional T cell types with gene expression profiles associated with innate effector functions and characterized the functional diversity of pig iNKT cells. These findings provide important insights into pig T cell development.
Article
Allergy
Rafael Gras-Pena, Nichole M. Danzl, Mohsen Khosravi-Maharlooei, Sean R. Campbell, Amanda E. Ruiz, Christopher A. Parks, William Meng Suen Savage, Markus A. Holzl, Debanjana Chatterjee, Megan Sykes
Summary: This study developed a novel differentiation protocol to generate human thymic epithelial progenitors from human embryonic stem cells (hES-TEPs) and demonstrated their thymopoietic function in vivo. By incorporating hES-TEPs into a supportive thymic structure, the researchers enhanced human thymocyte development and increased the reconstitution of peripheral CD4+ naive T cells.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Allergy
Maryam Ghaedi, Fumio Takei
Summary: Innate lymphoid cells (ILCs) mainly reside at barrier surfaces and play a regulatory role in tissue homeostasis and immunity. They are divided into 3 groups based on similar effector programs to T cells, and their development from lymphoid progenitors in adult mouse bone marrow has been extensively studied.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xian-Dong Liu, Peng-Hui Ai, Xiao-Na Zhu, Yuan-Bo Pan, Michael M. Halford, Mark Henkemeyer, Dong-Fu Feng, Tian-Le Xu, Suya Sun, Nan-Jie Xu
Summary: The research identifies a specific PDZ scaffold protein, Lnx1, expressed in the hippocampal CA3 region that is critical for initial social behavior. Deficiency of Lnx1 leads to neuronal activity disorders and social memory impairments, along with cognitive defects, in mice. It is found that Lnx1 deletion causes NMDA receptor hypofunction, disrupting the Lnx1-NMDAR-EphB2 complex and affecting synaptic function and social memory.
MOLECULAR PSYCHIATRY
(2021)
Review
Medicine, General & Internal
David Alfaro, Mariano R. Rodriguez-Sosa, Agustin G. Zapata
JOURNAL OF CLINICAL MEDICINE
(2020)
Article
Biotechnology & Applied Microbiology
Miguel Angel Rodriguez-Milla, Alvaro Morales-Molina, Ana Judith Perise-Barrios, Teresa Cejalvo, Javier Garcia-Castro
Summary: The study found that ICOCAV17 induces a more limited host response in canine MSCs, which may be related to a better clinical outcome; Infection of human MSCs with ICOVIR-5 increased the phosphorylation of a number of proteins, including AKT and c-JUN.
CANCER GENE THERAPY
(2021)
Article
Hematology
Sara Fananas-Baquero, Israel Orman, Federico Becerra Aparicio, Silvia Bermudez de Miguel, Jordi Garcia Merino, Rosa Yanez, Yolanda Fernandez Sainz, Rebeca Sanchez, Mercedes Dessy-Rodriguez, Omaira Alberquilla, David Alfaro, Agustin Zapata, Juan A. Bueren, Jose Carlos Segovia, Oscar Quintana-Bustamante
Summary: This study found that natural estrogens E2 and E4 can expand human hematopoietic stem and progenitor cells, with E4 being the most tolerated estrogen that promotes cycling of human hematopoietic progenitors. Additionally, E2 and E4 can double human hematopoietic engraftment in immunodeficient mice without altering other HSPC properties, potentially mediated through the regulation of mesenchymal stromal cells in the bone marrow niche.
Article
Oncology
Berta Segura-Collar, Maria Garranzo-Asensio, Beatriz Herranz, Esther Hernandez-SanMiguel, Teresa Cejalvo, Barbara S. Casas, Ander Matheu, Angel Perez-Nunez, Juan Manuel Sepulveda-Sanchez, Aurelio Hernandez-Lain, Veronica Palma, Ricardo Gargini, Pilar Sanchez-Gomez
Summary: This study identifies the EGFR-related mechanisms that govern the capacity of glioma cells to transdifferentiate into pericytes, regulating the vascular and immune phenotypes of the tumors.
Article
Multidisciplinary Sciences
Mahmoud S. Ahmed, Ping Wang, Ngoc Uyen Nhi Nguyen, Yuji Nakada, Ivan Menendez-Montes, Muhammad Ismail, Robert Bachoo, Mark Henkemeyer, Hesham A. Sadek, Enas S. Kandil
Summary: Previous studies showed that tetracycline antibiotics demeclocycline, chlortetracycline, and minocycline can inhibit EphB1 kinase activity, which was further confirmed in vivo by inhibiting phosphorylation of EphB1 in mice and effectively blocking neuropathic pain. This suggests that these drugs could be repurposed for treating neuropathic pain and potentially other conditions that benefit from inhibition of EphB1 receptor kinase activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Editorial Material
Immunology
Sara Montero-Herradon, Javier Garcia-Ceca, Agustin G. Zapata
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Cell Biology
David Garcia-Bernal, Mariano Garcia-Arranz, Rosa M. Yanez, Rosario Hervas-Salcedo, Alfonso Cortes, Maria Fernandez-Garcia, Miriam Hernando-Rodriguez, Oscar Quintana-Bustamante, Juan A. Bueren, Damian Garcia-Olmo, Jose M. Moraleda, Jose C. Segovia, Agustin G. Zapata
Summary: MSCs are widely used in advanced therapies for various purposes, mainly related to inflammatory processes. Despite their demonstrated efficacy in preclinical models and early clinical trials, there are still controversies regarding their specific phenotype, delivery methods, and varied cell products. Strategies for bioengineering MSCs are being explored to enhance their properties and functional capabilities.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Zhimin Huang, Simeng Liu, Anna Tang, Laith Al-Rabadi, Mark Henkemeyer, Patrice N. Mimche, Yufeng Huang
Summary: The study reveals that EphB2 receptor tyrosine kinase plays a key role in renal fibrosis, with its expression and activation being closely associated with fibrotic development following kidney injury.
Article
Hematology
Lidia M. Fernandez-Sevilla, Jaris Valencia, Paula Ortiz-Sanchez, Alberto Fraile-Ramos, Pilar Zuluaga, Eva Jimenez, Rosa Sacedon, Maria V. Martinez-Sanchez, Janez Jazbec, Marusa Debeljak, Birthe Fedders, Martin Stanulla, Denis Schewe, Gunnar Cario, Alfredo Minguela, Manuel Ramrez, Alberto Varas, Angeles Vicente
Summary: A retrospective study found that BMP4 expression levels in leukemic cells could serve as a new biomarker for prognosis in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). High BMP4 expression was associated with higher relapse rates and worse survival outcomes. Furthermore, BMP4 may be a potential therapeutic target for blocking leukemic central nervous system disease.
Article
Immunology
Silvia Sevilla-Movilla, Patricia Fuentes, Yaiza Rodriguez-Garcia, Nohemi Arellano-Sanchez, Peter W. Krenn, Soledad Isern de Val, Sara Montero-Herradon, Javier Garcia-Ceca, Valeria Burdiel-Herencia, Sofia R. Gardeta, Noemi Aguilera-Montilla, Celia Barrio-Alonso, Georgiana Crainiciuc, Daniel Bouvard, Angeles Garcia-Pardo, Agustin G. Zapata, Andres Hidalgo, Reinhard Fassler, Yolanda R. Carrasco, Maria L. Toribio, Joaquin Teixido
Summary: ICAP-1 plays an important role in the development of SP CD8(+) thymocytes and the control of marginal zone B-cell numbers.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Javier Garcia-Ceca, Sara Montero-Herradon, Ana Gonzalez, Rosa Plaza, Agustin G. Zapata
Summary: The lack of EphA4 alters T-cell differentiation and the histological organization of the thymus, impacting various T cell subsets as well as the proportions of thymocytes selected positively and negatively.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Letter
Dermatology
Rosa Sacedon, M. Carmen de Arriba, Lucia Martinez-Santamaria, Rocio Maseda, Sara Herraiz-Gil, Eva Jimenez, Isabel Rosales, Lucia Quintana, Nuria Illera, Marta Garcia, Nora Butta, Ihosvany Fernandez-Bello, Su M. Lwin, Miguel Fernandez-Arquero, Carlos Leon, John A. Mcgrath, M. Angeles Vicente, Marcela del Rio, Raul de Lucas, Silvia Sanchez-Ramon, Maria Jose Escamez
BRITISH JOURNAL OF DERMATOLOGY
(2023)