Article
Multidisciplinary Sciences
Rachel K. Lex, Weiqiang Zhou, Zhicheng Ji, Kristin N. Falkenstein, Kaleigh E. Schuler, Kathryn E. Windsor, Joseph D. Kim, Hongkai Ji, Steven A. Vokes
Summary: The study challenges the current understanding that GLI3 repression is established before Hedgehog (HH) signaling and demonstrates that GLI3 is inert in the limb bud before HH onset. The loss of Gli3 does not increase target gene expression or accessibility, contrasting with post-HH signaling. GLI repression is established independently of HH signaling, but after its onset.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Faxiang Xu, Chunhao Deng, Zhili Ren, Liangyu Sun, Ya Meng, Weiwei Liu, Jianbo Wan, Guokai Chen
Summary: Exogenous lipids such as LPA can influence the metabolism of pluripotent stem cells and induce distinct phenotypes and transcriptome profiles in the cells, altering their primed state.
Article
Multidisciplinary Sciences
Margherita Coccia, Wivine Burny, Marie-Ange Demoitie, Paul Gillard, Robert A. van den Berg, Robbert van der Most
Summary: Transcriptional responses to adjuvanted vaccines can vary among populations due to individual differences in pathogen exposure and immunological memory. This study found that individuals with higher cell-mediated memory responses to TB had stronger transcriptional responses to the AS01-adjuvanted vaccine. However, after a second vaccination, the heterogeneity in responses decreased and became similar across all groups.
Article
Cell Biology
Jian Sun, Jaeho Yoon, Moonsup Lee, Hyun-Kyung Lee, Yoo-Seok Hwang, Ira O. Daar
Summary: The Zic5 transcription factor is critical for the differentiation of retinal pigmented epithelium (RPE) and the rod photoreceptor layer by suppressing Hedgehog signaling. Zic5 interacts with Gli3 and disrupts its homodimerization, resulting in Gli3 protein stabilization. This study provides insights into the role of Zic5 in regulating Gli3 stability for proper eye development.
Article
Multidisciplinary Sciences
Rene Yu-Hong Cheng, Joseph de Rutte, Cade Ellis K. Ito, Andee R. Ott, Lucie Bosler, Wei-Ying Kuo, Jesse Liang, Brian E. Hall, David J. Rawlings, Dino Di Carlo, Richard G. James
Summary: By accumulating secretions close to secreting cells held within cavity-containing hydrogel nanovials, this study establishes workflows to analyze IgG secretion from single human B cells and link it to surface markers and transcriptomes. Measurements using flow cytometry and imaging flow cytometry confirm the association between IgG secretion and CD38/CD138. Using oligonucleotide-labeled antibodies, the study identifies upregulated pathways associated with high IgG secretion and uncovers surrogate plasma cell surface markers. This method enables researchers to explore the links between genome and function, leading to discoveries in immunology and stem cell biology.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Eva-Sophie Wallner, Nina Tonn, Dongbo Shi, Laura Luzzietti, Friederike Wanke, Pascal Hunziker, Yingqiang Xu, Ilona Jung, Vadir Lopez-Salmeron, Michael Gebert, Christian Wenzl, Jan U. Lohmann, Klaus Harter, Thomas Greb
Summary: This study reveals that the protein complex of SMXL5 and OBE3 plays a crucial role in phloem development by establishing a phloem-specific chromatin conformation in the nucleus.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Yu Xia, Katalin Sandor, Joy A. Pai, Bence Daniel, Saravanan Raju, Renee Wu, Sunnie Hsiung, Yanyan Qi, Tenzin Yangdon, Mariko Okamoto, Chun Chou, Kamir J. Hiam-Galvez, Robert D. Schreiber, Kenneth M. Murphy, Ansuman T. Satpathy, Takeshi Egawa
Summary: The study reveals the heterogeneity and plasticity of CD4(+) T cells during chronic infection and tumor response, and highlights their population dynamics through a stable, bipotent intermediate state.
Article
Immunology
Thomas Ciucci, Melanie S. Vacchio, Ting Chen, Jia Nie, Laura B. Chopp, Dorian B. McGavern, Michael C. Kelly, Remy Bosselut
Summary: This study reveals that Bcl6 promotes the differentiation of memory cells primarily by repressing Blimp1, while it does not promote the differentiation of Tfh cells. These findings uncover distinct mechanisms underlying the differentiation of memory and Tfh CD4(+) cells and identify the Bcl6-Blimp1 axis as a potential target for promoting long-term memory T cell differentiation.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Pooja Kumari, Lars Harald Thuestad, Rafal Ciosk
Summary: The LIN-41/TRIM71 protein in Caenorhabditis elegans serves as a versatile regulator of mRNA fate, playing different roles in somatic and germline cells. In somatic cells, LIN-41 recognizes specific mRNA sequences and either triggers decay or represses translation. In the germline, LIN-41's targets and regulatory mechanisms are not well understood, but it has been suggested to indirectly control mRNA by interacting with other RNA-binding proteins. This study demonstrates that LIN-41 can directly regulate germline mRNA via specific sequence elements, identifying potential targets and validating one known target involved in chromatin modification.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Immunology
Sonia Villanueva-Hernandez, Mahsa Adib Razavi, Katinka A. van Dongen, Maria Stadler, Karelle de Luca, Niklas Beyersdorf, Armin Saalmueller, Wilhelm Gerner, Kerstin H. Mair
Summary: Antibody-secreting plasma cells in pigs have been understudied. This study identified cross-reactive antibodies against three transcription factors and characterized a distinct population of Blimp-1(+)IRF4(+) cells in multiple organs. The cells showed different immunoglobulin-class distribution based on anatomical location. A FACS-sorting strategy was developed for functional assays. These findings provide fundamental knowledge on porcine plasma cells and facilitate future studies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Chester J. Joyner, Ariel M. Ley, Doan C. Nguyen, Mohammad Ali, Alessia Corrado, Christopher Tipton, Christopher D. Scharer, Tian Mi, Matthew C. Woodruff, Jennifer Hom, Jeremy M. Boss, Meixue Duan, Greg Gibson, Danielle Roberts, Joel Andrews, Sagar Lonial, Inaki Sanz, F. Eun-Hyung Lee
Summary: This study reveals the mechanisms by which circulating antibody secreting cells (ASCs) transform into long-lived plasma cells (LLPCs). LLPCs in the bone marrow (BM) have distinct morphological, transcriptomic, and epigenetic features compared to blood ASCs. LLPCs up-regulate prosurvival genes while simultaneously downregulating pro-apoptotic genes. The study also demonstrates that blood ASCs can undergo similar morphological and molecular changes by mimicking the BM environment in vitro.
LIFE SCIENCE ALLIANCE
(2022)
Article
Immunology
Marcus James Robinson, Zhoujie Ding, Mark R. Dowling, Danika L. Hill, Rosela H. Webster, Craig McKenzie, Catherine Pitt, Kristy O'Donnell, Jesse Mulder, Erica Brodie, Philip D. Hodgkin, Nick C. Wong, Isaak Quast, David M. Tarlinton
Summary: By using a genetic reporter to track ASCs, we have investigated the mechanisms regulating ASC lifespan and persistence. We found that the lifespan of ASCs is heterogeneous, with only a small fraction surviving for more than 60 days. ASC longevity beyond 60 days is associated with a transcriptional program enriched in long-lived ASCs. Thus, ASC turnover is primarily governed by intrinsic lifespan limits, with population dynamics influenced by niche vacancy rather than displacement.
Article
Immunology
Emily Robinson, Matthew A. Care, Kieran Walker, Michelle Campbell, Reuben M. Tooze, Gina M. Doody
Summary: This study describes a methodology using BCR or TLR ligation to obtain phenotypically mature plasma cells that have exited the cell cycle and express a gene signature consistent with long-lived plasma cells. The transcriptomes of the plasma cells show variation depending on the initial stimuli, suggesting unique functional properties. Additionally, the study demonstrates alternative promoter choice in regulating the expression of the master transcription factor Blimp-1/Prdm1, with preferential maintenance of expression following exposure to TLR ligation. Therefore, this system provides a valuable model for further understanding plasma cell biology.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Yulong Wei, Timothy C. Davenport, Jack A. Collora, Haocong Katherine Ma, Delia Pinto-Santini, Javier Lama, Ricardo Alfaro, Ann Durr, Ya-Chi Ho
Summary: Understanding the proliferation and persistence of HIV-1-infected cells is crucial for eradicating HIV-1. By examining the transcription factor accessibility, transcriptome, surface proteins, HIV-1 DNA, and HIV-1 RNA of single CD4+ memory T cells, we identified specific transcription factor accessibility in latent and transcriptionally active HIV-1-infected cells. Additionally, a proliferation program was found to promote the survival of transcriptionally active HIV-1-infected cells. Different epigenetic programs were also involved in driving the heterogeneous cellular states of HIV-1-infected cells, including activation, cytotoxic effector differentiation, migration, and cell death.
Article
Immunology
Anna K. Kania, Madeline J. Price, Lou-Ella George-Alexander, Dillon G. Patterson, Sakeenah L. Hicks, Christopher D. Scharer, Jeremy M. Boss
Summary: This study demonstrates that H3K27 demethylases inhibit B cell differentiation.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Chen Yao, Guohua Lou, Hong-Wei Sun, Ziang Zhu, Yi Sun, Zeyu Chen, Daniel Chauss, E. Ashley Moseman, Jun Cheng, Marc A. D'Antonio, Wangke Shi, Junwei Shi, Kohei Kometani, Tomohiro Kurosaki, E. John Wherry, Behdad Afzali, Luca Gattinoni, Yuwen Zhu, Dorian B. McGavern, John J. O'Shea, Pamela L. Schwartzberg, Tuoqi Wu
Summary: The study shows that the transcriptional repressor BACH2 is crucial early after chronic viral infection in influencing CD8(+) T cells, enforcing a stem-like fate and suppressing the formation of exhausted cells.
Correction
Immunology
Chen Yao, Guohua Lou, Hong-Wei Sun, Ziang Zhu, Yi Sun, Zeyu Chen, Daniel Chauss, E. Ashley Moseman, Jun Cheng, Marc A. D'Antonio, Wangke Shi, Junwei Shi, Kohei Kometani, Tomohiro Kurosaki, E. John Wherry, Behdad Afzali, Luca Gattinoni, Yuwen Zhu, Dorian B. McGavern, John J. O'Shea, Pamela L. Schwartzberg, Tuoqi Wu
Article
Multidisciplinary Sciences
Tomoharu Yasuda, Yuichi Saito, Chisato Ono, Kazuhiko Kawata, Akemi Baba, Yoshihiro Baba
Summary: The CD19-iCre mouse model, with a T2A-iCre sequence inserted into the Cd19 locus, shows more effective Cre recombination in early B cell development compared to CD19-Cre mice. The B lineage-specific recombination in CD19-iCre mice is more stringent than that in Mb1-iCre mice. Additionally, the CD19-iCre model demonstrates superior deletion efficiency in IL10-floxed mice compared to CD19-Cre mice, making it a valuable tool for highly efficient gene targeting specific to the B cell compartment.
SCIENTIFIC REPORTS
(2021)
Review
Immunology
Shiyu Huang, Tomoharu Yasuda
Summary: The Epstein-Barr virus is common in humans and can lead to lymphoproliferative diseases which may develop into lymphoma. The immune system plays a role in monitoring EBV+ B cells to prevent tumor formation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biology
Tetsuya Sakurai, Mutsuko Kukimoto-Niino, Kazufumi Kunimura, Nana Yamane, Daiji Sakata, Ryosuke Aihara, Tomoharu Yasuda, Shigeyuki Yokoyama, Mikako Shirouzu, Yoshinori Fukui, Takehito Uruno
Summary: DOCK8 is a critical guanine-nucleotide exchange factor for the development and function of white blood cells, playing a vital role in spatial control of Cdc42 activity during interstitial leukocyte migration by binding to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). The DHR-1 domain of DOCK8 contains basic residues that are responsible for stereospecific recognition of phosphoinositides, essential for its function.
LIFE SCIENCE ALLIANCE
(2021)
Article
Genetics & Heredity
Akihiro Nita, Akinobu Matsumoto, Ronghao Tang, Chisa Shiraishi, Kazuya Ichihara, Daisuke Saito, Mikita Suyama, Tomoharu Yasuda, Gaku Tsuji, Masutaka Furue, Bumpei Katayama, Toshiyuki Ozawa, Teruasa Murata, Teruki Dainichi, Kenji Kabashima, Atsushi Hatano, Masaki Matsumoto, Keiichi I. Nakayama
Summary: Although long noncoding RNAs (lncRNAs) are typically not translated into proteins, some lncRNAs contain small ORFs that can be translated. TINCR-encoded ubiquitin-like protein (TUBL) accelerates keratinocyte proliferation and plays a key role in skin homeostasis and regeneration after injury.
Article
Pharmacology & Pharmacy
Hiroko Shiraki, Shigeru Tanaka, Yun Guo, Kana Harada, Izumi Hide, Tomoharu Yasuda, Norio Sakai
Summary: GPR3 is immediately induced by T cell stimulation and plays an important role in suppressing effector T cell activation.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
Shintaro Mise, Akinobu Matsumoto, Keisuke Shimada, Toshiaki Hosaka, Masatomo Takahashi, Kazuya Ichihara, Hideyuki Shimizu, Chisa Shiraishi, Daisuke Saito, Mikita Suyama, Tomoharu Yasuda, Toru Ide, Yoshihiro Izumi, Takeshi Bamba, Tomomi Kimura-Someya, Mikako Shirouzu, Haruhiko Miyata, Masahito Ikawa, Keiichi Nakayama
Summary: This study identifies two small peptides encoded by a testes-specific lncRNA, Gm9999, that are crucial for male fertility in mice. These peptides interact with VDAC and play a critical role in the formation of the mitochondrial sheath in spermatozoa.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Yasuo Kitajima, Ryoka Tsukahara, Shohei Nakamoto, Tomoharu Yasuda
Summary: This study compared two methods for isolating lymphocytes during muscle regeneration and found that the CD45-magnetic bead method had a higher efficiency in isolating T cells, B cells, and myogenic cells from injured muscle tissues.
Article
Immunology
Takuya Koike, Kentaro Fujii, Kohei Kometani, Noah S. Butler, Kenji Funakoshi, Shinya Yari, Junichi Kikuta, Masaru Ishii, Tomohiro Kurosaki, Wataru Ise
Summary: In this study, the authors employed a time-stamping method to study the decay of plasma cells and their relationship with different cell populations. The results showed that homeostatic plasma cells in the bone marrow and spleen were continuously replenished by newly generated B220(hi)MHC-IIhi populations that differentiated into long-lived plasma cell populations. Both germinal center-independent and germinal center-dependent plasma cells decayed similarly and entered the long-lived plasma cell pool. Compared to a specific subtype of plasma cells, the cells with better adhesion status in the bone marrow niches showed higher survival potential.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Geriatrics & Gerontology
Yuma Sugiyama, Tanenobu Harada, Yuka Kamei, Tomoharu Yasuda, Tomoji Mashimo, Akihiko Nishikimi, Mitsuo Maruyama
Summary: Senescent cells play a role in aging-related malfunctions and pathologies, but it remains unclear whether current models accurately reflect physiological senescence. This study developed a novel approach to eliminate p16-expressing cells and generated a new knock-in model, p16hCD2 mice, and an inducer called hCD2-SAP. The study confirmed p16-associated hCD2 expression in various tissues and found that targeting p16positive senescent cells partially restored aging-related phenotypes in T lymphocytes.
EXPERIMENTAL GERONTOLOGY
(2023)
Article
Cell Biology
Kentaro Inoue, Tomoharu Yasuda, Yoshihiro Baba, Tadashi Yamamoto, Tomohiro Kurosaki, Hisaaki Shinohara
Summary: In this study, the influence of TRAF6 on CBM formation and TAK1 and IKK activities was investigated using TRAF6-deficient DT40 B cells. Mathematical model analysis showed that TRAF6 contributes to the positive regulation of IKK activation via TAK1, and negatively regulates CARMA1 binding to Bcl10.
Article
Multidisciplinary Sciences
Wiebke Winkler, Carlota Farre Diaz, Eric Blanc, Hanna Napieczynska, Patrick Langner, Marvin Werner, Barbara Walter, Brigitte Wollert-Wulf, Tomoharu Yasuda, Arnd Heuser, Dieter Beule, Stephan Mathas, Ioannis Anagnostopoulos, Andreas Rosenwald, Klaus Rajewsky, Martin Janz
Summary: By targeting the expression of genes involved in MM subgroup-specific chromosomal translocations into mouse GC B cells, we have generated distinct MM-like disease models that recapitulate key features of human tumors, which provides insights into the pathogenesis and therapeutic vulnerabilities of different MM subgroups.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
Kiyomi Shitaoka, Akifumi Higashiura, Yohei Kawano, Akima Yamamoto, Yoko Mizoguchi, Takao Hashiguchi, Norihisa Nishimichi, Shiyu Huang, Ayano Ito, Shun Ohki, Miyuki Kanda, Tomohiro Taniguchi, Rin Yoshizato, Hitoshi Azuma, Yasuo Kitajima, Yasuyuki Yokosaki, Satoshi Okada, Takemasa Sakaguchi, Tomoharu Yasuda
Summary: Broadly neutralizing antibodies against SARS-CoV-2 variants, including Omicron, were found in long-term hospitalized convalescent patients infected with early SARS-CoV-2 strain B.1.1, and their mechanisms were identified through crystal structures. The decrease in antibody efficacy against mutated SARS-CoV-2 spike RBD explains breakthrough infections and reinfections by Omicron variants. Therefore, eliciting RBD-specific B cells in the longitudinal germinal center reaction provides potent immunity against emerging wide range of SARS-CoV-2 variants.
COMMUNICATIONS BIOLOGY
(2023)
Article
Immunology
Hitoshi Azuma, Yohei Kawano, Kiyomi Shitaoka, Takahiro Kawahara, Ayano Ito, Akifumi Higashiura, Yasuo Kitajima, Shun Ohki, Tomoharu Yasuda
Summary: The multiple amino acid replacements in the receptor-binding domain (RBD) of the Omicron variant of SARS-CoV-2 weaken the effectiveness of antibodies elicited by current booster vaccines. There is a concern regarding the original antigenic sin negative aspect of the immune response that needs to be addressed. However, our study shows that vaccination with Omicron-specific antigens can induce a broad range of neutralizing antibodies against Omicron variants, even in individuals previously vaccinated with the original antigen.
INTERNATIONAL IMMUNOLOGY
(2023)