Article
Cell Biology
Rebecca J. Burgess, Zhiyu Zhao, Daisuke Nakada, Sean J. Morrison
Summary: The study showed that deficiency of Bmi1 leads to increased division of HSCs without inducing senescence. Bmi1 promotes HSC quiescence by negatively regulating ARX expression and promoting proteostasis by suppressing protein synthesis.
GENES & DEVELOPMENT
(2022)
Article
Hematology
Isabel Hidalgo, Martin Wahlestedt, Ouyang Yuan, Qinyu Zhang, David Bryder, Cornelis Jan Pronk
Summary: The Polycomb complex protein Bmi1 is a master regulator of hematopoietic stem cells (HSCs). It plays an important role in HSC maintenance and self-renewal. Stabilizing the levels of Bmi1 over time can protect HSCs from transplantation-related stress.
EXPERIMENTAL HEMATOLOGY
(2022)
Article
Multidisciplinary Sciences
Jinzhong Qin, Congcong Wang, Yaru Zhu, Ting Su, Lixia Dong, Yikai Huang, Kunying Hao
Summary: Polycomb group (PcG) proteins impact stem cell identity and fate decisions through unknown mechanisms, with the gene Mga playing a role in repressing the endodermal transcription factor Gata6. Deletion of Mga in ESCs leads to impaired self-renewal and spontaneous differentiation to primitive endoderm.
Review
Cell & Tissue Engineering
Heyao Zhang, Xuepeng Wang, Jingsheng Li, Ronghua Shi, Ying Ye
Summary: This review summarizes the functional and mechanistic studies of the BAF complex in mouse ESCs and early embryonic development. It highlights the discussion on the distinct phenotypes resulting from the deletion of different BAF subunits in ESCs and embryos.
STEM CELLS INTERNATIONAL
(2021)
Review
Biochemistry & Molecular Biology
Amira Fitieh, Andrew J. Locke, Mobina Motamedi, Ismail Hassan Ismail
Summary: Polycomb group proteins play roles in stem cell maintenance, gene silencing, and DNA damage repair. BMI1, a member of PRC1, is involved in DNA repair and genome integrity, making it a potential pharmacological target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Yuting Fu, Fangyuan Liu, Shuo Cao, Jia Zhang, Huizhi Wang, Baojiang Wu, Yongli Song, Shuguang Duo, Xihe Li, Siqin Bao
Summary: This study reveals that Bdh2 deficiency has no impact on pluripotency and self-renewal of ESCs, but promotes endoderm differentiation and is essential for maintaining DNA methylation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Liuyan Huang, Feifei Li, Ling Ye, Fanyuan Yu, Chenglin Wang
Summary: Dynamic chromatin accessibility controls gene expression, regulating stem cell fate determination and tissue homeostasis. Polycomb repressive complex 2 (PRC2), as a histone-modifying enzyme that predominantly mediates methylation of lysine 27 in histone H3 (H3K27me1/2/3), plays a canonical role in targeting developmental regulators during stem cell differentiation. Embryonic ectoderm development (EED), the core scaffold subunit of PRC2 and an H3K27me3-recognizing protein, is involved in PRC2 stabilization and allosterically stimulated PRC2. Experimental data suggest that EED-associated epigenetic modifications are essential for stem cell maintenance and differentiation. This review discusses the structural architecture of EED, its contributions, and underlying mechanisms in mediating lineage differentiation of different stem cells during epigenetic modification to enhance our understanding of PRC2.
CELL PROLIFERATION
(2023)
Article
Oncology
Molly M. M. Wilson, Paul S. S. Danielian, Griffin Salus, Roberta Ferretti, Charles A. A. Whittaker, Jacqueline A. A. Lees
Summary: BMI1 is involved in the self-renewal and proliferation of adult stem cells and tumors, but in cutaneous melanoma, it promotes epithelial-mesenchymal transition and metastasis while having little effect on proliferation or primary tumor growth. Deletion of melanocyte-specific Bmi1 in mice leads to premature hair greying and gradual loss of melanocytes, and depilation accelerates the depletion of melanocyte stem cells, suggesting a protective role of BMI1 against stress in these cells.
PIGMENT CELL & MELANOMA RESEARCH
(2023)
Article
Multidisciplinary Sciences
Eniko Sutus, Surya Henry, Lili Adorjan, Gergo Kovacs, Melinda Katalin Pirity
Summary: This study reveals the important role of RYBP in mouse neural development by regulating Pax6 and the RA signaling pathway. The results suggest that RYBP promotes progenitor formation by repressing Pax6 expression, and the increased activity of the RA signaling pathway further enhances this effect.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Jun Yu, Cong Shen, Meng Lin, Xia Chen, Xiuliang Dai, Zhiran Li, Yunhao Wu, Yangbo Fu, Jinxing Lv, Xiaoyan Huang, Bo Zheng, Fei Sun
Summary: In this study, we identified BMI1 as a key regulator of spermatogonial stem cell (SSC) maintenance. BMI1 represses target genes by increasing H2AK119ub and reducing H3K4me3 in SSCs. Additionally, BMI1 inhibition activates Wnt signaling and promotes nuclear translocation of beta-catenin in SSCs. Suppression of Wnt/beta-catenin signaling restores SSC maintenance in BMI1-deficient SSCs. Our findings not only reveal a novel mechanism for BMI1 in SSC maintenance, but also provide a potential strategy for treating male infertility.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Satoshi Nakata, Ming Yuan, Jeffrey A. Rubens, Ulf D. Kahlert, Jarek Maciaczyk, Eric H. Raabe, Charles G. Eberhart
Summary: CNS-BCOR ITD is a malignant entity with a specific oncogenic mechanism, the impact on the biology of neuroepithelial cells is not well understood. BCOR-ITD promotes derepression of PRC2-target genes, but no growth advantage was observed in human neural stem cells, while enhanced cell growth, invasion, and migration were seen in murine cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell & Tissue Engineering
Emmanuelle Julien, Katia Biasch, Reine El Omar, Jean-Noel Freund, Christian Gachet, Francois Lanza, Manuela Tavian
Summary: The study found that angiotensin-converting enzyme is expressed in hematopoietic progenitors in developing mouse embryos and various elements of the renin-angiotensin system are present in specific regions of human and mouse embryos. Experimentally, angiotensin II signaling is crucial for the generation of hematopoietic cells, with the peptide stimulating hematopoiesis in culture.
Article
Medicine, Research & Experimental
Wei Shan, Liping Zhou, Lizhen Liu, Deju Lin, Qin Yu
Summary: In this study, iPSCs were reprogrammed from somatic cells and differentiated into neurons through induction, with the key role of Bmi1 in the process highlighted.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Cell Biology
Keita Yamamoto, Susumu Goyama, Shuhei Asada, Takeshi Fujino, Taishi Yonezawa, Naru Sato, Reina Takeda, Akiho Tsuchiya, Tomofusa Fukuyama, Yosuke Tanaka, Akihiko Yokoyama, Hikaru Toya, Ayana Kon, Yasuhito Nannya, Rena Onoguchi-Mizutani, Shinichi Nakagawa, Tetsuro Hirose, Seishi Ogawa, Nobuyoshi Akimitsu, Toshio Kitamura
Summary: The study reveals that ASXL1 plays a role in the formation of paraspeckles, and a pathogenic ASXL1-MT mutation can disrupt paraspeckles and reduce the interactions between non-coding RNA NEAT1 and protein NONO.
Article
Cell Biology
Chenze Xu, Ali Mohsin, Yanxia Luo, Lili Xie, Yan Peng, Qizheng Wang, Waqas Ahmed, Haifeng Hang, Yingping Zhuang, Meijin Guo
Summary: In this study, non-genetically modified Sertoli-like cells were successfully induced from mouse ESCs using defined protein factors, showing similar characteristics and functionality to natural Sertoli cells. However, the efficiency of the non-GM method was still lower compared to lentiviral transduction. This work lays a foundation for the future production of non-GM Sertoli-like cells for clinical applications and fundamental theory research.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sophia Kirschke, Ireti Ogunsulire, Balachandar Selvakumar, Neele Schumacher, Tanya Sezin, Stefan Rose-John, Alexander Scheffold, Christoph Garbers, Juliane Lokau
Summary: The cytokine IL-2 plays a crucial role in immune homeostasis. This study demonstrates that metalloproteases ADAM10 and ADAM17 can cleave the IL-2R alpha, generating a soluble ectodomain that inhibits IL-2 signaling in T cells. Manipulating the cleavage of IL-2R alpha offers a potential opportunity to alter IL-2 function.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Torben Mentrup, Anna Yamina Stumpff-Niggemann, Nadja Leinung, Christine Schlosser, Katja Schubert, Rebekka Wehner, Antje Tunger, Valentin Schatz, Patrick Neubert, Ann-Christine Gradtke, Janina Wolf, Stefan Rose-John, Paul Saftig, Alexander Dalpke, Jonathan Jantsch, Marc Schmitz, Regina Fluhrer, Ilse D. Jacobsen, Bernd Schroeder
Summary: Dectin-1 plays a critical role in recognizing fungal pathogens through pattern recognition receptors on immune cells. Activation of Dectin-1a results in the formation of a stable receptor fragment lacking the ligand binding domain, which contributes to signal transduction in phagosomal membranes and is terminated by intramembrane proteases SPPL2a and 2b.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Maria Angeles Rodriguez-Hernandez, David Carneros, Maria Nunez-Nunez, Ramon Coca, Rosario Baena, Gema M. Lopez-Ruiz, Maria Elena Cano-Serrano, Alberto Martinez-Telleria, Ana Fuentes-Lopez, Juan Manuel Praena-Fernandez, Christoph Garbers, Jose Hernandez-Quero, Federico Garcia, Stefan Rose-John, Matilde Bustos
Summary: IL-6 signaling variables serve as useful tools for early identification and stratification of COVID-19 patients, with significant implications for treatment and clinical decision-making.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, General & Internal
Tor Henrik Anderson Tvedt, Stefan Rose-John, Galina Tsykunova, Aymen Bushra Ahmed, Tobias Gedde-Dahl, Elisabeth Ersvaer, Oystein Bruserud
Summary: Graft-versus-host disease (GVHD) is a common complication after stem cell transplantation and is mediated by T cells. IL-6 plays a role in both pro-inflammatory and anti-inflammatory effects, and it modulates T cell response. The study found that CD3(+)CD4(+) and CD3(+)C8(+) T cells have different responses to IL-6 signaling, and these responses are influenced by antithymocyte globulin treatment. These findings suggest that IL-6 targeting after transplantation may have varied effects on patients.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Medicine, Research & Experimental
Mor Paldor, Orr Levkovitch-Siany, Dana Eidelshtein, Revital Adar, Claes D. Enk, Yitzhak Marmary, Sharona Elgavish, Yuval Nevo, Hadar Benyamini, Inbar Plaschkes, Shiri Klein, Alex Mali, Stefan Rose-John, Amnon Peled, Eithan Galun, Jonathan H. Axelrod
Summary: This study reveals the molecular and cellular basis of irradiation-induced alopecia and dermatitis (IRIAD). Senescence-associated IL-6 and IL-1 signaling, IL-17 upregulation, and CCR6(+)-mediated immune cell migration are the key drivers of IRIAD. Genetic ablation and molecular inhibition of these pathways alleviate IRIAD symptoms.
EMBO MOLECULAR MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Dominik M. Schulte, Georg H. Waetzig, Harald Schuett, Marlies Marx, Berenice Schulte, Christoph Garbers, Juliane Lokau, Ann-Kathrin Vlacil, Juliane Schulz, Anna K. Seoudy, Bernhard Schieffer, Philip Rosenstiel, Marcus Seeger, Matthias Laudes, Stefan Rose-John, Ulf Luetzen, Karsten Grote, Stefan Schreiber
Summary: Inflammation plays an important role in atherosclerotic cardiovascular disease, and there is a need for therapies targeting excessive inflammation. A fusion protein called olamkicept has been shown to reduce atherosclerosis independently of LDL cholesterol metabolism in mice, and its use in a patient with high-risk ASCVD also demonstrated a reduction in arterial wall inflammation.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Immunology
Aikaterini Gatsiou, Simon Tual-Chalot, Matteo Napoli, Almudena Ortega-Gomez, Tommy Regen, Rachit Badolia, Valeriana Cesarini, Claudia Garcia-Gonzalez, Raphael Chevre, Giorgia Ciliberti, Carlos Silvestre-Roig, Maurizio Martini, Jedrzej Hoffmann, Rana Hamouche, Joseph R. Visker, Nikolaos Diakos, Astrid Wietelmann, Domenico Alessandro Silvestris, Georgio Georgiopoulos, Ali Moshfegh, Andre Schneider, Wei Chan, Stefan Guenther, Johanne Backs, Shin Kwak, Craig H. Selzman, Kimon Stamatelopoulos, Stefan Rose-John, Christian Trautwein, Ioakim Spyridopoulos, Thomas Braun, Ari Waisman, Angela Gallo, Stavros G. Drakos, Stefanie Dimmeler, Markus Sperandio, Oliver Soehnlein, Konstantinos Stellos
Summary: RNA editor ADAR2 regulates endothelial responses to IL-6, controlling leukocyte trafficking in inflamed and ischemic tissues. ADAR2 is required for IL-6 trans-signaling and immune cell infiltration through suppressing primary microRNA processing.
Article
Neurosciences
Stephan A. Muller, Merav D. Shmueli, Xiao Feng, Johanna Tushaus, Neele Schumacher, Ryan Clark, Brad E. Smith, An Chi, Stefan Rose-John, Matthew E. Kennedy, Stefan F. Lichtenthaler
Summary: In this study, the researchers identified SEZ6 and gp130/IL6ST as physiological substrates of BACE1 in non-human-primate cerebrospinal fluid. They also found a reduction of gp130 in human CSF from a clinical trial with a BACE inhibitor and in plasma of BACE1-deficient mice. These findings provide insights into the relationship between BACE1 and gp130 in neuronal signaling and survival.
MOLECULAR NEURODEGENERATION
(2023)
Article
Immunology
Agatha Schwarz, Rebecca Philippsen, Serena G. Piticchio, Jan N. Hartmann, Robert Haesler, Stefan Rose-John, Thomas Schwarz
Summary: The organ-specific microbiome, particularly the skin microbiome, plays a crucial role in tissue homeostasis by regulating the inflammatory response. Short chain fatty acids (SCFA) induce regulatory T cells (Treg) in the skin and their signal is mediated by the receptor HCA2. Knock-out of HCA2 results in stronger inflammation and a switch of Treg from a suppressive to a proinflammatory type, indicating that the skin microbiome dictates the outcome of the inflammatory reaction.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Stefan Rose-John, Brendan J. Jenkins, Christoph Garbers, Jens M. Moll, Juergen Scheller
Summary: This review discusses the discovery of the IL-6 trans-signalling pathway and the development of biologics that specifically inhibit this pathway. Targeting IL-6 trans-signalling can decrease disease-promoting activities of IL-6 without blocking its protective actions.
NATURE REVIEWS IMMUNOLOGY
(2023)
Meeting Abstract
Immunology
P. Bradtke, J. Roesch, D. Reimers, K. Yan, S. Rose-John, H. -W. Mittruecker
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Meeting Abstract
Immunology
E. V. M. Huth, L. C. Heinig, K. Yan, P. Bradtke, N. Lory, T. Wiech, S. Rose-John, H. -W. Mittruecker
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Meeting Abstract
Oncology
Melanie Spitzner, Kristin Koerdel, Thomas Meyer, Niklas Engels, Florian Krause, Jochen Gaedcke, Lena-Christin Conradi, Martin Haubrock, Tim Beissbarth, Andreas Leha, Steven A. Johnsen, B. Michael Ghadimi, Stefan Rose-John, Jurgen Wienands, Marian Grade
ONCOLOGY RESEARCH AND TREATMENT
(2022)
Meeting Abstract
Ophthalmology
Kristin Hoesel, Buesra Chasan, Christoph Ehlken, Jan Tode, Stefan Rose-John, Johann Roider
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Meeting Abstract
Gastroenterology & Hepatology
Nofar Rosenberg, Matthias Van Haele, Maria Garcia Beccaria, Mirian Fernandez-Vaquero, Danijela Heide, Neta Barashi, Amnon Peled, Yuval Nevo, Shrona Elgavish, Dirk Schmist-Arras, Hanan Edler, Alina Simerzin, Michal Shoshkes-Carmel, Klaus Kaestner, Hilla Giladi, Stefan Rose-John, Tania Roskams, Mathias Heikenwalder, Eithan Galun
JOURNAL OF HEPATOLOGY
(2022)
