Review
Oncology
Benluvankar Varghese, Nunzio Del Gaudio, Gilda Cobellis, Lucia Altucci, Angela Nebbioso
Summary: Breast cancer is the second leading cause of cancer death in women, with genetic mutations and epigenetic modifications playing a critical role in its progression. The KDM4 enzymes are considered potential therapeutic targets for breast cancer, but the lack of selective inhibitors has hindered their entry into clinical trials.
FRONTIERS IN ONCOLOGY
(2021)
Article
Plant Sciences
Jinping Cheng, Linhao Xu, Valentin Berger, Astrid Bruckmann, Chao Yang, Veit Schubert, Klaus D. Grasser, Arp Schnittger, Binglian Zheng, Hua Jiang
Summary: This study reveals that H3K9 demethylases IBM1 and JMJ27 cooperatively regulate meiotic progression and protect protein-coding genes from ectopic H3K9me2 modification in Arabidopsis thaliana. They also interact with the cohesin complex cofactor PDS5, independently of H3K9 demethylation, to regulate male meiosis and gene expression.
Article
Chemistry, Medicinal
Qiong Wu, Brandon Young, Yan Wang, Andrew M. Davidoff, Zoran Rankovic, Jun Yang
Summary: The KDM4 family plays a crucial role in gene transcription, DNA repair, and metabolism, and its dysregulation is linked to various human disorders. Developing selective and potent KDM4 inhibitors holds great promise for understanding its role in these disorders and providing therapeutic opportunities.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Shirly Becker-Herman, Milena Rozenberg, Carmit Hillel-Karniel, Naama Gil-Yarom, Mattias Kramer, Avital Barak, Lital Sever, Keren David, Lihi Radomir, Hadas Lewinsky, Michal Levi, Gilgi Friedlander, Richard Bucala, Amnon Peled, Idit Shachar
Summary: This study reveals that mice lacking CD74 exhibit accumulation of HSCs in the bone marrow, suggesting that CD74 may regulate the maintenance of HSCs and CD18 expression. Blocking CD74 also increases the numbers of HSPCs, which could improve transplant protocols.
Article
Oncology
Rosalie G. Hoyle, Huiqun Wang, Yana Cen, Yan Zhang, Jiong Li
Summary: The study reveals that in human colorectal cancer, KDM3 may play a more essential role than KDM4 in regulating the Wnt signaling, and that IOX1, a known histone demethylase inhibitor, significantly suppresses Wnt target gene transcription and colorectal cancer tumorigenesis through inhibiting KDM3 enzymatic activity.
MOLECULAR CANCER THERAPEUTICS
(2021)
Review
Cell Biology
Delia Cicciarello, Laurent Schaeffer, Isabella Scionti
Summary: Adult skeletal muscle is composed of multinucleated muscle fibers and has the ability to regenerate. The fate of muscle stem cells is determined by intrinsic and extrinsic factors as well as the expression of specific gene subsets. Histone demethylases play a crucial role in the fate choice of muscle stem cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Qingnan Tian, Yujia Sun, Tingting Gao, Jiaxin Li, Huimin Fang, Shoutao Zhang
Summary: SUMOylation and ubiquitylation are crucial processes in eukaryotic biology, with Djubc9 and Djnedd4L identified as important factors in head regeneration in planarians through RNA-seq analysis. RNA interference experiments confirmed their roles in stem cell maintenance and regeneration processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Yinghui Li, Chaoqun Wang, Huier Gao, Jiali Gu, Yiran Zhang, Yingyi Zhang, Min Xie, Xuelian Cheng, Ming Yang, Wenshan Zhang, Yafang Li, Mei He, Hui Xu, Hexiao Zhang, Qing Ji, Tianhua Ma, Sheng Ding, Yu Zhao, Yingdai Gao
Summary: This study identified a specific KDM4 inhibitor, SD49-7, for resistant leukemia therapy, demonstrating its ability to inhibit the progression of leukemia stem cells (LSCs) and overcome resistance to traditional treatments.
Article
Biochemistry & Molecular Biology
Shaoli Zhou, Xue Li, Qian Liu, Yu Zhao, Wei Jiang, Anqi Wu, Dao-Xiu Zhou
Summary: The study revealed that DNA methylation is locally reconfigured after fertilization and intensified during embryogenesis in rice. Three rice DNA glycosylases, DNG702, DNG701, and DNG704, were found to demethylate DNA at distinct genomic regions in gametes and zygotes, playing a crucial role in zygotic gene expression and development. The results suggest that active DNA demethylation in gametes and zygotes is critical for gene expression and reproduction in rice.
Article
Engineering, Biomedical
Victoria Barnhouse, Nathan Petrikas, Cody Crosby, Janet Zoldan, Brendan Harley
Summary: The study developed and characterized a three-dimensional perivascular tissue model to investigate the influence of the perivascular secretome on HSC behavior, finding that perivascular conditioned media promoted maintenance of a greater fraction of hematopoietic stem and progenitor cells within a 4-day culture period.
ANNALS OF BIOMEDICAL ENGINEERING
(2021)
Review
Oncology
Li Xuan, Qifa Liu
Summary: Relapse is still the main reason for treatment failure in AML patients undergoing allo-HSCT. Evidence suggests that maintenance therapy post-transplantation, particularly targeted drugs like hypomethylating agents, FLT3 inhibitors, and isocitrate dehydrogenase inhibitors, could benefit AML patients, especially those at high risk.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Biology
Virginia Folgado-Marco, Kristina Ames, Jacky Chuen, Kira Gritsman, Nicholas E. Baker
Summary: A conditional knockout mouse was generated by partially deleting Rps12. Mice inheriting the Rps12(KO/+) genotype exhibited growth and morphological defects, pancytopenia, and impaired erythropoiesis. There was a significant reduction in hematopoietic stem cells and progenitors in the bone marrow of Rps12(KO/+) mice.
Article
Cell & Tissue Engineering
Melany Jackson, Antonella Fidanza, A. Helen Taylor, Stanislav Rybtsov, Richard Axton, Maria Kydonaki, Stephen Meek, Tom Burdon, Alexander Medvinsky, Lesley M. Forrester
Summary: The Apelin receptor plays a crucial role in the production of HSPCs from mesodermal cells and its signaling pathway is required for their generation. However, the activation of APLNR signaling impairs the maintenance of long-term reconstituting HSPCs and drives myeloid differentiation, suggesting a dual role in hematopoiesis.
Article
Cell Biology
Changhong Du, Xinmiao Wang, Yiding Wu, Weinian Liao, Jiachuan Xiong, Yingguo Zhu, Chaonan Liu, Wenhao Han, Yue Wang, Songling Han, Shilei Chen, Yang Xu, Song Wang, Fengchao Wang, Ke Yang, Jinghong Zhao, Junping Wang
Summary: The soluble Klotho and inorganic phosphate (Pi) are identified as extrinsic factors that antagonistically regulate hematopoietic stem cell (HSC) maintenance. Renal Klotho deficiency or Pi excess leads to Pi overload in the bone marrow microenvironment and Pi retention in HSCs, altering the maintenance of HSCs.
Article
Cell Biology
Nico Zaghet, Katrine Madsen, Federico Rossi, Daniel Fernandez Perez, Pier Giorgio Amendola, Samuel Demharter, Ulrich Pfisterer, Konstantin Khodosevich, Diego Pasini, Anna Elisabetta Salcini
Summary: The research found that jmjd-5 regulates H3K36 and H3K27 methylation levels by controlling gene expression, maintaining germ cell immortality and protecting cell identity. H3K36/K27 demethylases play a role in the transcriptional framework, promoting the balance between H3K36 and H3K27 methylation.
Article
Hematology
Jan-Erik Messling, Karl Agger, Kasper L. Andersen, Kristina Kromer, Hanna M. Kuepper, Anders H. Lund, Kristian Helin
Summary: Novel therapies are urgently needed for the treatment of acute myeloid leukemia (AML). A study identified RIOK2 as a potential target for AML treatment, as its loss leads to decreased protein synthesis and apoptosis in leukemic cells.
Article
Cell & Tissue Engineering
Wei Gu, Hua Wang, Xiaofeng Huang, Judith Kraiczy, Pratik N. P. Singh, Charles Ng, Sezin Dagdeviren, Sean Houghton, Oscar Pellon-Cardenas, Ying Lan, Yaohui Nie, Jiaoyue Zhang, Kushal K. Banerjee, Emily J. Onufer, Brad W. Warner, Jason Spence, Ellen Scherl, Shahin Rafii, Richard T. Lee, Michael P. Verzi, David Redmond, Randy Longman, Kristian Helin, Ramesh A. Shivdasani, Qiao Zhou
Summary: SATB2 plays a crucial role in maintaining the identity of adult colonic stem cells and epithelial cells in mice and humans.
Article
Biochemistry & Molecular Biology
Dawei Huo, Zhaowei Yu, Rui Li, Meihan Gong, Simone Sidoli, Xukun Lu, Yuying Hou, Zhongye Dai, Yu Kong, Guifen Liu, Ole N. Jensen, Wei Xie, Kristian Helin, Chaoyang Xiong, Guohong Li, Yong Zhang, Xudong Wu
Summary: This study reveals the dynamic chromatin configuration of CGIs during exit from naive pluripotency and provides a conceptual framework for the spatiotemporal establishment of PcG functions.
Article
Biology
Morteza Chalabi Hajkarim, Ella Karjalainen, Mikhail Osipovitch, Konstantinos Dimopoulos, Sandra L. Gordon, Francesca Ambri, Kasper Dindler Rasmussen, Kirsten Gronbaek, Kristian Helin, Krister Wennerberg, Kyoung-Jae Won
Summary: In this article, the authors introduce a toolkit called compaRe for large-scale multiparameter data analysis. The toolkit integrates quality control, data bias correction, and data visualization methods, and provides faster and more reliable analysis results through a mass-aware gridding algorithm-based similarity analysis. The results show that compaRe can reveal interpatient heterogeneity and recognizable phenotypic profiles, as well as identify multiple types of phenotypic response patterns in drug response data.
Article
Biology
Xiaokang Wang, Wojciech Rosikiewicz, Yurii Sedkov, Tanner Martinez, Baranda S. Hansen, Patrick Schreiner, Jesper Christensen, Beisi Xu, Shondra M. Pruett-Miller, Kristian Helin, Hans-Martin Herz
Summary: This study identifies PROSER1 as a regulator of TET2 O-GlcNAcylation and its role in DNA demethylation. PROSER1 mediates the interaction between OGT and TET2, promoting TET2 O-GlcNAcylation and protein stability. Furthermore, PROSER1 colocalizes with UTX, TET1/2, and OGT on many genomic elements, suggesting its involvement in regulating chromatin-associated proteins via OGT-mediated O-GlcNAcylation.
LIFE SCIENCE ALLIANCE
(2022)
Article
Hematology
Bing Li, Wenbin An, Hua Wang, Timour Baslan, Shoron Mowla, Aishwarya Krishnan, Wenbin Xiao, Richard P. Koche, Ying Liu, Sheng F. Cai, Zhijian Xiao, Andriy Derkach, Ilaria Iacobucci, Charles G. Mullighan, Kristian Helin, Scott W. Lowe, Ross L. Levine, Raajit K. Rampal
Summary: Leukemic transformation (LT) of myeloproliferative neoplasm (MPN) is often fatal, with TP53 mutational inactivation being the most common event. This study demonstrates that biallelic inactivation of Trp53 leads to LT, specifically a pure erythroleukemia (PEL), arising from the megakaryocyte-erythroid progenitor population. Activation of the bone morphogenetic protein 2/SMAD pathway contributes to abnormal self-renewal of megakaryocyte-erythroid progenitors during LT. The Jak2/Trp53 mutant PEL is characterized by recurrent copy number alterations and DNA damage, and combination WEE1 and poly(ADP-ribose) polymerase inhibition shows potential as a therapeutic strategy.
Article
Multidisciplinary Sciences
Hua Wang, Zheng Fan, Pavel V. Shliaha, Matthew Miele, Ronald C. Hendrickson, Xuejun Jiang, Kristian Helin
Summary: Using mouse embryonic stem cells, we found that acute ablation of shared subunits of the SET1/COMPASS complexes leads to a complete loss of all H3K4 methylation. H3K4me3 turnover is faster than H3K4me1 and H3K4me2, and it relies on KDM5 demethylases. Acute loss of H3K4me3 does not affect transcriptional initiation but results in decreased transcriptional output, increased RNAPII pausing, and slower elongation.
Correction
Multidisciplinary Sciences
Hua Wang, Zheng Fan, Pavel V. Shliaha, Matthew Miele, Ronald C. Hendrickson, Xuejun Jiang, Kristian Helin
News Item
Genetics & Heredity
Chang Huang, Kristian Helin
Summary: New research suggests that histone H2B N terminus multisite lysine acetylation (H2BNTac) is a significant characteristic of active enhancers and could greatly enhance enhancer prediction accuracy.
Article
Biochemistry & Molecular Biology
Zhen Sun, Yuan Lin, Mohammed T. Islam, Richard Koche, Lin Hedehus, Dingyu Liu, Chang Huang, Thomas Vierbuchen, Charles L. Sawyers, Kristian Helin
Summary: Nuclear receptor-binding SET-domain protein 1 (NSD1) is a crucial methyltransferase involved in transcriptional regulation and is dysregulated in diseases like Sotos syndrome. NSD1 associates with H3K36me2 at regulatory elements, particularly enhancers. It promotes enhancer-dependent gene transcription by facilitating RNA polymerase II pause release, affecting cell fate transition and Sotos syndrome development.
Article
Multidisciplinary Sciences
Stine L. Hansen, Hjalte L. Larsen, Laura M. Pikkupeura, Grzegorz Maciag, Jordi Guiu, Iris Muller, Ditte L. Clement, Christina Mueller, Jens Vilstrup Johansen, Kristian Helin, Mads Lerdrup, Kim B. Jensen
Summary: By studying mouse fetal and adult small intestinal organoids, it was found that rare adult-like cells exist in fetal organoids, suggesting that fetal organoids have the potential to mature but are regulated by certain factors. Through a CRISPR-Cas9 screen, Smarca4 and Smarcc1 were identified as important factors for maintaining the immature progenitor state. This study demonstrates the usefulness of organoid models in identifying factors regulating cell fate and state transitions during tissue maturation and reveals the role of SMARCA4 and SMARCC1 in preventing precocious differentiation during intestinal development.
Editorial Material
Oncology
Helene Damhofer, Kristian Helin
Summary: The dense desmoplastic stroma in pancreatic cancer hinders successful immune-mediated tumor control. Recent research shows that inhibiting EZH2 can relieve the suppressive effect of tumor stroma, allowing for increased expression of pro-inflammatory chemokines after therapy-induced senescence. This boost in NK and T cell recruitment enhances immunological tumor control.
Article
Multidisciplinary Sciences
Anne Meldgaard Hansen, Ying Ge, Mikkel Bruhn Schuster, Sachin Pundhir, Janus Schou Jakobsen, Adrija Kalvisa, Marta Cecylia Tapia, Sandra Gordon, Francesca Ambri, Frederik Otzen Bagger, Deo Pandey, Kristian Helin, Bo Torben Porse
Summary: The study reveals that H3K9me2 is crucial for the proliferation of AML and its loss leads to activation of the interferon pathway. Mechanistically, destabilization of a complex involving SUV39H1, G9A, and GLP is responsible for this activation.
