Article
Biology
Yunyun Zou, Nobuhiko Kamada, Seung-Yong Seong, Sang-Uk Seo
Summary: This study explores the phenotypic and functional heterogeneity of myeloid-derived suppressor cells (MDSCs) in tumor-bearing hosts. It identifies CD115(-) monocytic MDSCs as a distinct subtype with the potential to differentiate into OLFM4(hi) polymorphonuclear MDSCs. CD115(-) monocytic MDSCs increase in the blood and bone marrow as tumors progress, while preferentially differentiating into tumor-associated macrophages in the tumor mass.
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Pauliina M. Munne, Lahja Martikainen, Iiris Raty, Kia Bertula, Nonappa, Janika Ruuska, Hanna Ala-Hongisto, Aino Peura, Babette Hollmann, Lilya Euro, Kerim Yavuz, Linda Patrikainen, Maria Salmela, Juho Pokki, Mikko Kivento, Juho Vaananen, Tomi Suomi, Liina Nevalaita, Minna Mutka, Panu Kovanen, Marjut Leidenius, Tuomo Meretoja, Katja Hukkinen, Outi Monni, Jeroen Pouwels, Biswajyoti Sahu, Johanna Mattson, Heikki Joensuu, Paivi Heikkila, Laura L. Elo, Ciara Metcalfe, Melissa R. Junttila, Olli Ikkala, Juha Klefstrom
Summary: Researchers found that matrix stiffness regulates ERα expression via stress-mediated p38 activation and H3K27me3-mediated epigenetic regulation, revealing a crucial mechanobiological component in hormonal signaling in breast tissue.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Lucille Stuani, Marie Sabatier, Estelle Saland, Guillaume Cognet, Nathalie Poupin, Claudie Bosc, Florence A. Castelli, Lara Gales, Evgenia Turtoi, Camille Montersino, Thomas Farge, Emeline Boet, Nicolas Broin, Clement Larrue, Natalia Baran, Madi Y. Cisse, Marc Conti, Sylvain Loric, Tony Kaoma, Alexis Hucteau, Aliki Zavoriti, Ambrine Sahal, Pierre-Luc Mouchel, Mathilde Gotanegre, Cedric Cassan, Laurent Fernando, Feng Wang, Mohsen Hosseini, Emeline Chu-Van, Laurent Le Cam, Martin Carroll, Mary A. Selak, Norbert Vey, Remy Castellano, Francois Fenaille, Andrei Turtoi, Guillaume Cazals, Pierre Bories, Yves Gibon, Brandon Nicolay, Sebastien Ronseaux, Joseph R. Marszalek, Koichi Takahashi, Courtney D. DiNardo, Marina Konopleva, Vera Pancaldi, Yves Collette, Floriant Bellvert, Fabien Jourdan, Laetitia K. Linares, Christian Recher, Jean-Charles Portais, Jean-Emmanuel Sarry
Summary: Mutations in IDH lead to enhanced mitochondrial oxidative metabolism in AML, involving increased electron transport chain activity and fatty acid oxidation. IDH1 mutant inhibitors reduce 2-HG levels and CEBPα methylation, but do not reverse fatty acid oxidation and OxPHOS. Targeting mitochondrial activities may improve anti-AML efficacy of IDH mutant inhibitors.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
David Milewski, Samriddhi Shukla, Berkley E. Gryder, Arun Pradhan, Johnny Donovan, Parvathi Sudha, Sushmitha Vallabh, Athena Pyros, Yan Xu, Artem Barski, Sara Szabo, Brian Turpin, Joseph G. Pressey, Douglas P. Millay, Javed Khan, Vladimir V. Kalinichenko, Tanya Kalin
Summary: The FOXF1 transcription factor plays a crucial role in FP-RMS tumorigenesis by regulating gene expression associated with FP-RMS gene signature. By cooperating with PAX3-FOXO1 and E-box transcription factors, FOXF1 functions downstream of PAX3-FOXO1 to promote the development of FP-RMS.
Article
Multidisciplinary Sciences
Carter J. Barger, Abigail K. Suwala, Katarzyna M. Soczek, Albert S. Wang, Min Y. Kim, Chibo Hong, Jennifer A. Doudna, Susan M. Chang, Joanna J. Phillips, David A. Solomon, Joseph F. Costello
Summary: TERT promoter duplications have the same functional significance as hotspot mutations, leading to tumor cell immortality, and are clonal in patients with multifocal glioblastoma.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Longlong Liu, Pradeep Kumar Patnana, Xiaoqing Xie, Daria Frank, Subbaiah Chary Nimmagadda, Minhua Su, Donghua Zhang, Thorsten Koenig, Frank Rosenbauer, Marie Liebmann, Luisa Klotz, Wendan Xu, Jan Vorwerk, Felix Neumann, Jana Huve, Andreas Unger, Jurgen Gunther Okun, Bertram Opalka, Cyrus Khandanpour
Summary: Recent studies have revealed the important role of transcription factor GFI1B in metabolic regulation during hematopoiesis and leukemia development. Gfi1b deletion leads to activation of mitochondrial respiration and alteration of energy metabolism towards oxidative phosphorylation (OXPHOS). Gfi1b also epigenetically regulates multiple genes involved in fatty acid oxidation (FAO). The correlation between Gfi1b expression level and metabolic phenotype is influenced by genetic variations in AML cells. Inhibition of FAO or OXPHOS significantly hinders leukemia progression, and Gfi1b-deficient AML cells are more sensitive to drugs targeting OXPHOS and FAO, suggesting new potential therapeutic strategies.
Article
Multidisciplinary Sciences
Guolun Wang, Bingqiang Wen, Zicheng Deng, Yufang Zhang, Olena A. Kolesnichenko, Vladimir Ustiyan, Arun Pradhan, Tanya Kalin, Vladimir V. Kalinichenko
Summary: The molecular mechanisms through which pulmonary endothelial progenitor cells stimulate lung angiogenesis have been revealed to be the activation of the BMP9/ACVRL1/SMAD1 signaling pathway by FOXF1 and FLI1 nuclear proteins. This discovery contributes to a better understanding of the regulation of lung angiogenesis.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Mengjia Li, Penglei Jiang, Kai Cheng, Zehui Zhang, Shuyu Lan, Xiaoxia Li, Lirong Zhao, Yucheng Wang, Xiang Wang, Jing Chen, Tao Ji, Bingshe Han, Junfang Zhang
Summary: The enhancer elements at -34k are crucial for MYB expression, with transcription factor binding and epigenetic modifications playing key roles in this process.
CELL DEATH & DISEASE
(2021)
Article
Multidisciplinary Sciences
Rita Silverio-Alves, Ilia Kurochkin, Anna Rydstrom, Camila Vazquez Echegaray, Jakob Haider, Matthew Nicholls, Christina Rode, Louise Thelaus, Aida Yifter Lindgren, Alexandra Gabriela Ferreira, Rafael Brandao, Jonas Larsson, Marella F. T. R. de Bruijn, Javier Martin-Gonzalez, Carlos-Filipe Pereira
Summary: The transcription factor GATA2 plays a critical role in definitive hematopoiesis by bookmarking genomic sites during mitosis. Its retention on chromatin during cell division is important for lineage commitment.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Xinhui Zhao, Boris Bartholdy, Yukiya Yamamoto, Erica K. Evans, Meritxell Alberich-Jorda, Philipp B. Staber, Touati Benoukraf, Pu Zhang, Junyan Zhang, Bon Q. Trinh, John D. Crispino, Trang Hoang, Mahmoud A. Bassal, Daniel G. Tenen
Summary: The transcription factor PU.1 recruits c-Jun as a co-activator to promoters without AP-1 binding sites, which is crucial for macrophage differentiation.
COMMUNICATIONS BIOLOGY
(2022)
Article
Plant Sciences
Jinhui Man, Yue Shi, Yuying Huang, Xiaoqin Zhang, Xin Wang, Shanhu Liu, Gaojie He, Kelu An, Dongran Han, Xiaohui Wang, Shengli Wei
Summary: In this study, a transcription factor named PnMYB4 was found to repress the accumulation of saponins in P. notoginseng. It interacts with PnbHLH and competes with the activator PnMYB1 to modulate saponin biosynthesis. This provides theoretical basis for improving the content of saponins and efficacy of P. notoginseng.
HORTICULTURE RESEARCH
(2023)
Article
Plant Sciences
Rui Zhang, Yitong Shen, Juanxia He, Chenyan Zhang, Yelin Ma, Chenghui Sun, Xiaopan Song, Li Li, Sisi Zhang, Janos Barnabas Biro, Farheen Saifi, Peter Kalo, Rujin Chen
Summary: Forward genetics and transcriptomic analyses identified NCR343 as a crucial nodule-specific cysteine-rich peptide in Medicago truncatula, playing a key role in the differentiation and/or maintenance of bacteroids. Loss-of-function of NCR343 resulted in impaired bacteroid differentiation and/or maintenance, as well as premature nodule senescence. Subcellular localization studies confirmed the colocalization of NCR343 with bacteroids in symbiosomes within infected nodule cells. Transcriptomic analyses revealed upregulation of senescence-related genes in ncr343 mutant nodules. Overall, these findings demonstrate the essential role of NCR343 in symbiotic nitrogen fixation.
Article
Multidisciplinary Sciences
Jingying Zhou, Huanyu Wang, Ting Shu, Jing Wang, Weiqin Yang, Jingqing Li, Lipeng Ding, Man Liu, Hanyong Sun, John Wong, Paul Bo-san Lai, Shun-Wa Tsang, Simon E. Ward, King-Lau Chow, Joseph Jao-yiu Sung, Alfred Sze-Lok Cheng
Summary: Massive expansion of immature and suppressive myeloid cells is a common feature of malignant solid tumors. Over-expression of cyclin-dependent kinase 20 in hepatocellular carcinoma correlates with reduced patient survival and low immunotherapy responsiveness. Here, we showed that CCRK is upregulated in myeloid cells in tumor-bearing mice and in patients with HCC. Inactivation of Ccrk in myeloid cells confers a mature phenotype and increases IL-12 production, leading to reduced tumor growth and prolonged survival. Mechanistically, CCRK activates STAT3/E4BP4 signaling to induce immunosuppression. Our findings provide insights into MDSC-mediated immunosuppression and offer a potential kinase-target for cancer immunotherapy.
Article
Multidisciplinary Sciences
Jeffrey R. Haswell, Kaia Mattioli, Chiara Gerhardinger, Philipp G. Maass, Daniel J. Foster, Paola Peinado, Xiaofeng Wang, Pedro P. Medina, John L. Rinn, Frank J. Slack
Summary: This study describes a method to modulate lncRNA expression during human embryonic stem cell differentiation and identifies key lncRNA loci involved in differentiation. A clustering approach was developed to infer mechanisms of action of lncRNA hits, leading to the validation of FOXD3-AS1 as a functional lncRNA essential for pluripotency and differentiation. The cell lines and methodology presented in this study can be adapted to discover and characterize novel regulators of differentiation into any lineage.
Article
Immunology
Gretchen Harms Pritchard, Anthony T. Phan, David A. Christian, Trevor J. Blain, Qun Fang, John Johnson, Nathan H. Roy, Lindsey Shallberg, Ross M. Kedl, Christopher A. Hunter
Summary: T-bet is a key regulator of CD4(+) Th1 differentiation and IFN-gamma production, but its importance in CD8(+) T cell response has been less certain. In this study, we found that T-bet expression in CD8(+) T cells is required for optimal expansion of parasite-specific effector CD8(+) T cells following vaccination with a replication-deficient strain of Toxoplasma gondii. Analysis of early T cell activation events revealed that T-bet regulates the upregulation of LFA1 alpha chain CD11a in CD8(+) T cells, which influences the initial priming of CD8(+) effector T cells. These findings suggest that early expression of T-bet is an intrinsic factor in T cells that optimizes T-DC interactions necessary for generating effector responses.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)