Article
Immunology
Miho Shinzawa, E. Ashley Moseman, Selamawit Gossa, Yasuko Mano, Abhisek Bhattacharya, Terry Guinter, Amala Alag, Xiongfong Chen, Maggie Cam, Dorian B. McGavern, Batu Erman, Alfred Singer
Summary: The study found that the fate of T cell lineages is determined by coreceptor proteins encoded by Cd4 and Cd8 gene loci, rather than the strength of the coreceptor signal. Additionally, the researchers suggest that evolution selected specific coreceptor proteins to prevent the generation of functionally reversed T cells.
Article
Multidisciplinary Sciences
Samantha E. Hoffman, Todd W. Dowrey, Carlos Villacorta Martin, Kevin Bi, Breanna Titchen, Shreya Johri, Laura Dellostritto, Miraj Patel, Colin Mackichan, Stephanie Inga, Judy Chen, Grace Grimaldi, Sara Napolitano, Isaac Wakiro, Jingyi Wu, Jason Yeung, Asaf Rotem, Ewa Sicinska, Erin Shannon, Thomas Clancy, Jiping Wang, Sarah Denning, Lauren Brais, Naomi R. Besson, Kathleen L. Pfaff, Ying Huang, Katrina Z. Kao, Scott Rodig, Jason L. Hornick, Sebastien Vigneau, Jihye Park, Matthew H. Kulke, Jennifer Chan, Eliezer M. Van Allen, George J. Murphy
Summary: This study investigated the single-cell transcriptomes of patients with gastroenteropancreatic NETs and found the transcriptomic heterogeneity of neuroendocrine tumor cells and the influence of tumor microenvironment on tumor pathophysiology, revealing potential avenues for future precision medicine therapeutics.
Article
Medicine, General & Internal
Anna Sobus, Bartlomiej Baumert, Monika Golab-Janowska, Piotr Kulig, Edyta Paczkowska, Karolina Luczkowska, Dorota Roginska, Alicja Zawislak, Slawomir Milczarek, Bogumila Osekowska, Wioletta Pawlukowska, Agnieszka Meller, Karolina Machowska-Sempruch, Agnieszka Welnicka, Przemyslaw Nowacki, Boguslaw Machalinski
Summary: The study demonstrated a significant decrease in plasma C3b concentration and a peak clinical improvement on days 7-28 after intrathecal administrations of Lin(-) cells in ALS patients. Additionally, a decrease in neutrophil count and CRP level was observed on days 5-7 post-cell injection. These findings suggest that Lin(-) cell therapy may have potential benefits in treating ALS by modulating the complement-mediated immune system.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Immunology
Tania M. Villanueva-Cabello, Lya D. Gutierrez-Valenzuela, Roberta Salinas-Marin, Delia V. Lopez-Guerrero, Ivan Martinez-Duncker
Summary: Polysialic acid (polySia) is a regulated polymer in mammals that influences cell interactions, and it plays significant roles in the immune system. However, there is still much to be explored regarding the regulation mechanisms and signaling networks of polySia.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Mireia Guerau-de-Arellano, Zayda L. L. Piedra-Quintero, Philip N. Tsichlis
Summary: Akt, a PI3K-activated serine-threonine kinase, plays important roles in immune cell development and effector functions in both innate and adaptive immune cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Marcos C. Vieira, Celeste M. Donato, Philip Arevalo, Guus F. Rimmelzwaan, Timothy Wood, Liza Lopez, Q. Sue Huang, Vijaykrishna Dhanasekaran, Katia Koelle, Sarah Cobey
Summary: Based on statistical modeling of surveillance data from New Zealand, historical changes and cross-protection between different strains of the same lineage were found to explain the contrasting age distributions of influenza B cases. Additional protection against B/Yamagata was observed in individuals with first-time influenza B infections, resembling immune imprinting seen in influenza A. While data did not show evidence of B/Victoria imprinting, B/Yamagata imprinting could explain the fewer cases in certain cohorts and the bimodal age distribution. Longitudinal studies are needed to validate these findings across different populations and more recent strains.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Joshua Warrick, Wenhuo Hu, Hironobu Yamashita, Vonn Walter, Lauren Shuman, Jenna M. Craig, Lan L. Gellert, Mauro A. A. Castro, A. Gordon Robertson, Fengshen Kuo, Irina Ostrovnaya, Judy Sarungbam, Ying-bei Chen, Anuradha Gopalan, Sahussapont J. Sirintrapun, Samson W. Fine, Satish K. Tickoo, Kwanghee Kim, Jasmine Thomas, Nagar Karan, Sizhi Paul Gao, Timothy N. Clinton, Andrew T. Lenis, Timothy A. Chan, Zhiyu Chen, Manisha Rao, Travis J. Hollman, Yanyun Li, Nicholas D. Socci, Shweta Chavan, Agnes Viale, Neeman Mohibullah, Bernard H. Bochner, Eugene J. Pietzak, Min Yuen Teo, Gopa Iyer, Jonathan E. Rosenberg, Dean F. Bajorin, Matthew Kaag, Suzanne B. Merrill, Monika Joshi, Rosalyn Adam, John A. Taylor, Peter E. Clark, Jay D. Raman, Victor E. Reuter, Yu Chen, Samuel A. Funt, David B. Solit, David J. DeGraff, Hikmat A. Al-Ahmadie
Summary: Squamous differentiation in bladder cancer is associated with genomic and immunologic heterogeneity and resistance to immunotherapy. The loss of FOXA1, GATA3, and PPARG expression is involved in lineage plasticity and dysregulation of PD-L1 expression.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Daniel Atar, Anna-Sophia Mast, Sophia Scheuermann, Lara Ruoff, Christian Martin Seitz, Patrick Schlegel
Summary: CD19CAR T cells show promising results in treating relapsed and refractory aggressive B-lineage cancers. The AdCAR technology allows multitargeting and flexibility in adapting to different antigen profiles, increasing treatment effectiveness and overcoming antigen immune escape.
Review
Hematology
Celine Overbeeke, Tamar Tak, Leo Koenderman
Summary: The article discusses the production and homeostasis regulation of neutrophils, as well as the factors involved in their proliferation and differentiation. Neutrophil homeostasis is influenced by both intracellular and extracellular mechanisms and is maintained through feedback loops. The article also examines conflicting data regarding the replenishment of the neutrophil pool.
Review
Immunology
Chen Wang, Lydia Kay Lutes, Coline Barnoud, Christoph Scheiermann
Summary: The immune system is regulated by circadian rhythms, and recent advances have identified molecular factors governing these rhythms. The interconnectivity between immune cells and their environment has been found to be highly complex.
SCIENCE IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Ke-Huan K. Chow, Mark W. Budde, Alejandro A. Granados, Maria Cabrera, Shinae Yoon, Soomin Cho, Ting-Hao Huang, Noushin Koulena, Kirsten L. Frieda, Long Cai, Carlos Lois, Michael B. Elowitz
Summary: By utilizing the intMEMOIR system, researchers have developed a method to record cell lineage information that can be read out in situ. This system allows for lineage reconstruction in both mouse and fly cells, as well as simultaneous analysis of clonal history, spatial position, and gene expression. These results establish a foundation for microscopy-readable lineage recording and analysis in diverse systems.
Review
Genetics & Heredity
Vallari Shukla, Anna Cetnarowska, Mette Hyldahl, Susanne Mandrup
Summary: This article reviews recent advances in the understanding of the interplay between chromatin topology and transcription, revealing that lineage determination and differentiation depend on the dynamic chromatin topology, forming transcriptional hubs.
TRENDS IN GENETICS
(2022)
Review
Immunology
Marc Daeron
Summary: Progress in neuroimmunology has revealed the functional relationship between the nervous and immune systems. While they both have similar communication mechanisms and influence each other, they differ in anatomical structure, response to stimuli, and target of action. The close collaboration of these systems allows the organism to adapt and coexist with the environment and other organisms.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biology
Vania Lopez Ruiz, Jacques Robert
Summary: Amphibians play a crucial role in bridging the evolutionary gap between mammals and ancient vertebrates. Understanding their immune system, which is similar to that of mammals, is important for disease research. The African clawed frog, Xenopus laevis, is a good model for studying the immune system, particularly during early development stages. This review summarizes the knowledge about the innate and adaptive immune system of X. laevis and compares it with other amphibians. It also discusses the response of amphibians to viral, bacterial, and fungal infections.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Tian Zeng, Saleem Jaffar, Yijuan Xu, Yixiang Qi
Summary: Insects have developed unique intestinal defenses against microorganism invasion, including physical barriers like the peritrophic matrix and mucus layer, as well as immune responses such as antimicrobial peptides and reactive oxygen species. The janus kinase/STAT signaling pathway and melanization play important roles in insect intestinal immunity. The coordination of the intestinal immune defense system and intestinal tissue renewal is essential in effectively defending against pathogens.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Maile Romero-Wolf, Boyoung Shin, Wen Zhou, Maria Koizumi, Ellen Rothenberg, Hiroyuki Hosokawa
JOURNAL OF CELL BIOLOGY
(2020)
Review
Hematology
Ellen V. Rothenberg, Berthold Gottgens
Summary: This review discusses how Eric H. Davidson's work has influenced the understanding of hematopoietic cell fate determination through gene regulation, highlighting the discoveries of key regulatory factors and the importance of gene regulatory network models in explaining complex regulatory processes in blood and immune cell development.
CURRENT OPINION IN HEMATOLOGY
(2021)
Review
Hematology
Ellen V. Rothenberg
Summary: Recent studies have revealed a robustly conserved core program in early T-cell precursors in mice and humans, with some informative variations between species and ontogenic states. The T-cell program is closely related to dendritic cell programs, especially plasmacytoid dendritic cells in humans.
EXPERIMENTAL HEMATOLOGY
(2021)
Article
Multidisciplinary Sciences
Boyoung Shin, Hiroyuki Hosokawa, Maile Romero-Wolf, Wen Zhou, Kaori Masuhara, Victoria R. Tobin, Ditsa Levanon, Yoram Groner, Ellen Rothenberg
Summary: Runx1 and Runx3 play redundant, collaborative roles in regulating genes crucial for T cell development, with a preference for activating T-lineage genes and repressing multipotent progenitor genes during lineage commitment. The two factors show extensive shift in binding sites and exhibit stage-specific activation or repression of target genes, contributing to a developmental ratchet mechanism making commitment irreversible. Runx1 and Runx3 also coordinate their occupancies at clustered sites around positively or negatively regulated targets during commitment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Victor Olariu, Mary A. Yui, Pawel Krupinski, Wen Zhou, Julia Deichmann, Emil Andersson, Ellen Rothenberg, Carsten Peterson
Summary: This study presents a three-level dynamic model to explain the commitment dynamics of thymic cell development, including a core gene regulatory network architecture, stochastically controlled chromatin-state gate, and single-cell proliferation model.
Review
Biophysics
Ellen Rothenberg
Summary: Transcription factors play a crucial role in initiating changes in gene expression by reading regulatory sequence information in the genome. Their actions are guided by site-specific DNA binding and target sequence specificities, but are also influenced by chromatin states and interactions with other transcription factors. These factors can lead to emergent discontinuities in function, impacting the regulatory functions of key transcription factors.
BIOPHYSICAL JOURNAL
(2021)
Review
Immunology
Tom Sidwell, Ellen V. Rothenberg
Summary: Bcl11b, a critical transcription factor, plays context-dependent roles in the development of different cell types. Its chromatin binding activity is largely guided by interactions with other transcription factors, and it recruits multiple families of chromatin-modifying enzyme complexes to induce changes in regional suites of epigenetic modifications.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Hiroyuki Hosokawa, Maria Koizumi, Kaori Masuhara, Maile Romero-Wolf, Tomoaki Tanaka, Toshinori Nakayama, Ellen Rothenberg
Summary: The transcription factors Runx1 and GATA3 have been found to regulate Spi1 expression levels in pro-T cells, controlling the repression of Spi1 during T lineage commitment. This regulation is achieved through a specific intronic silencing element in mouse Spi1.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Immunology
Wen Zhou, Fan Gao, Maile Romero-Wolf, Suin Jo, Ellen Rothenberg
Summary: This study reveals the role of transcription factors in early T cell development through the use of single-cell RNA-seq and gene disruption strategies. The findings demonstrate a dynamic competition between early-acting transcription factors before T cell commitment, and the activation of Bcl11b transcription factor alters ongoing cellular programs.
SCIENCE IMMUNOLOGY
(2022)
Editorial Material
Immunology
Ellen Rothenberg
JOURNAL OF IMMUNOLOGY
(2022)
Review
Immunology
Brendan W. MacNabb, Ellen V. Rothenberg
Summary: T-cell differentiation is a regulated developmental process controlled by transcription factors and chromatin landscapes, and influenced by signals from the thymic stroma. Differentiation is driven by changing combinations of TFs and involves multiple checkpoints. Fetal T-cell development differs from adult and involves unique populations of innate lymphoid cells and invariant gamma delta T cells. Recent single-cell transcriptome data provide insights into the TF networks involved in T-cell differentiation in the fetal and adult mouse thymus.
IMMUNOLOGICAL REVIEWS
(2023)
Review
Immunology
Boyoung Shin, Ellen V. V. Rothenberg
Summary: T cells develop from multipotent progenitors through a process regulated by intrathymic Notch signaling and extensive proliferation. This process is controlled by multiple transcription factors, some associated with stemness, some with alternative lineages, and others specifically involved in T-cell fate. The network of interactions between these factors has been well characterized, shedding light on the stages and mechanisms of T-cell lineage commitment.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Boyoung Shin, Wen Zhou, Jue Wang, Fan Gao, Ellen V. Rothenberg
Summary: Runx factors regulate lineage specification of hematopoietic cells, including T lymphocytes, by binding to specific genomic regions. In early T cell development, dynamic Runx binding shifts are regulated by Runx dosage and functional partners rather than local chromatin state. Limited Runx protein availability leads to premature Runx occupancy at post-commitment binding sites, accelerating T cell lineage development. This regulation involves the activation of T cell-identity and innate lymphoid cell programs by Runx and other transcription factors. Overall, Runx proteins play a crucial role in directing lineage-fate decisions in various cell types.
Article
Immunology
Rosanne Spolski, Peng Li, Vivek Chandra, Boyoung Shin, Shubham Goel, Keiko Sakamoto, Chengyu Liu, Jangsuk Oh, Min Ren, Yutaka Enomoto, Erin E. West, Stephen M. Christensen, Edwin C. K. Wan, Meili Ge, Jian-Xin Lin, Bingyu Yan, Majid Kazemian, Zu-Xi Yu, Keisuke Nagao, Pandurangan Vijayanand, Ellen V. Rothenberg, Warren J. Leonard
Summary: The IL-2 receptor alpha chain is regulated by distinct super-enhancer elements, which control constitutive and inducible expression in a cell type-specific manner. Deletion of these elements leads to autoimmune diseases and altered CD25 expression, providing new insights into cell type-specific regulation of CD25.
SCIENCE IMMUNOLOGY
(2023)
Review
Immunology
Hiroyuki Hosokawa, Ellen Rothenberg
Summary: Transcription factors play essential roles in early thymic development to establish T cell lineage identity by controlling the activities of specific genomic loci. The interactions between inherited epigenetic states, transcription factor-DNA binding affinity thresholds, and influences of given transcription factors on other factors in the same cells determine T cell identity and make the lineage choice irreversible.
NATURE REVIEWS IMMUNOLOGY
(2021)
