Article
Cell Biology
Mingzhu Wang, Kun Zhao, Meng Liu, Mengting Wang, Zhibin Qiao, Shanru Yi, Yonghua Jiang, Xiaochen Kou, Yanhong Zhao, Jiqing Yin, Tianming Li, Hong Wang, Cizhong Jiang, Shaorong Gao, Jiayu Chen
Summary: A deficiency in bone morphogenetic protein (BMP) signaling in chemically defined medium can impair pluripotency in mouse embryonic stem cells (mESCs), but activating BMP signaling with BMP4 can safeguard chromosomal integrity and proliferation capacity of mESCs, promoting in vivo developmental potential and long-term pluripotency preservation.
Article
Cell Biology
Xiaoying Ye, Chenglei Tian, Linlin Liu, Guofeng Feng, Kairang Jin, Haiying Wang, Jiyu Chen, Lin Liu
Summary: It has been shown that oncostatin M (OSM) can replace leukemia inhibitory factor (LIF) to maintain naive pluripotency in ESCs. Mouse ESCs cultured in OSM exhibit similar pluripotency gene expression levels and developmental pluripotency as those cultured in LIF. Additionally, OSM activates the Stat3 signaling pathway and regulates certain metabolic pathways.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell & Tissue Engineering
Fangyuan Cheng, Mingyue Li, Rick Francis Thorne, Guangzhi Liu, Zhang Yuwei, Mian Wu, Lianxin Liu
Summary: This study reveals the importance of p21-activated kinase 4 (Pak4) in maintaining the pluripotency of murine embryonic stem cells (mESCs). The Nanog-Pak4-Akt signaling axis is essential for self-renewal of mESCs and plays a crucial role in somatic cell reprogramming.
Article
Cell Biology
Ramon Cesar Botigelli, Naira Carolina Godoy Pieri, Brendon William Bessi, Lucas Simoes Machado, Alessandra Bridi, Aline Fernanda de Souza, Kaiana Recchia, Paulo Fantinato Neto, Pablo Juan Ross, Fabiana Fernandes Bressan, Marcelo Fabio Gouveia Nogueira
Summary: Reprogramming fetal fibroblasts with transient expression of four transcription factors can generate bovine iPSC (biPSC) lines with pluripotency. Treatment with bFGF promotes efficient acquisition of pluripotency, while LIF2i treatment does not promote continuous self-renewal. The biPSC lines can differentiate into three embryonic layers and contribute to chimeric blastocysts.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell & Tissue Engineering
Yun-Sheng Yang, Man-Hua Liu, Zhao-Wen Yan, Guo-Qiang Chen, Ying Huang
Summary: In this study, researchers found that FAM122A plays a critical role in mesendodermal specification and cardiac differentiation. Its deficiency results in embryonic lethality, cardiovascular defects, and impaired cardiac functions. Further investigation revealed that Fam122a deficiency affects mesendodermal specification and cardiac differentiation from mouse embryonic stem cells through dysregulation of histone modification and Wnt and Hippo signaling pathways via modulation of PP2A activity. These findings significantly contribute to our understanding of the regulatory network of mesendodermal/cardiac differentiation and propose the potential importance of FAM122A in cardiac regeneration.
Review
Plant Sciences
Ying Wu, Xiang Li, Jinnan Zhang, Haiqing Zhao, Shaolin Tan, Wanhao Xu, Jiaqi Pan, Fan Yang, Erxu Pi
Summary: This review focuses on the Ethylene Responsive Factor (ERF) subfamily, which is the largest group of proteins in the plant AP2/ERF superfamily. The ERFs have been extensively studied for their role in regulating plant resistances to various abiotic stresses. The review summarizes the molecular mechanisms of ERF regulation and their impact on stress responsive gene transcription. However, there is limited comprehensive annotation of the interacting proteins and target genes of ERFs. Future research prospects include investigating the mechanisms of stress signal transmission to ERFs and the transcriptional regulation of stress responsive genes by ERFs.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Materials Science, Multidisciplinary
Xiao-Ping Li, Ke Deng, Botao Fu, YongKai Li, Da-Shuai Ma, JunFeng Han, Jianhui Zhou, Shuyun Zhou, Yugui Yao
Summary: In this study, a new type III Weyl semimetal is proposed, exemplified by (TaSe4) (2) I with larger chiral charges and gapless characteristics at room temperature. External strain can induce transitions among different types of Weyl semimetals in (TaSe4) (2) I, accompanied by Lifshitz transitions of the Fermi surfaces. The work experimentally identifies (TaSe4) (2) I as a type III Weyl semimetal and provides a platform for further investigation into the physics of type III Weyl fermions.
Article
Multidisciplinary Sciences
S. Bagnulo, A. Cellino, L. Kolokolova, R. Nezic, T. Santana-Ros, G. Borisov, A. A. Christou, Ph. Bendjoya, M. Devogele
Summary: Observations of interstellar comet 2I/Borisov show higher polarization and a more homogeneous coma compared to typical comets in our Solar System, suggesting a more pristine nature of this object.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Jiangbo Wei, Xianbin Yu, Lei Yang, Xuelian Liu, Boyang Gao, Boxian Huang, Xiaoyang Dou, Jun Liu, Zhongyu Zou, Xiao-Long Cui, Li-Sheng Zhang, Xingsen Zhao, Qinzhe Liu, P. Cody He, Caraline Sepich-Poore, Nicole Zhong, Wenqiang Liu, Yanhe Li, Xiaochen Kou, Yanhong Zhao, You Wu, Xuejun Cheng, Chuan Chen, Yiming An, Xueyang Dong, Huanyu Wang, Qiang Shu, Ziyang Hao, Tao Duan, Yu-Ying He, Xuekun Li, Shaorong Gao, Yawei Gao, Chuan He
Summary: This study reveals that FTO mediates m(6)A demethylation of LINE1 RNA in mouse embryonic stem cells, regulating LINE1 RNA abundance and the local chromatin state. It also plays regulatory roles in shaping chromatin state and gene expression during mouse oocyte and embryonic development.
Article
Biochemistry & Molecular Biology
Bingbing Yang, Xiaohua Yao, Yanru Zeng, Chengcai Zhang
Summary: The ethylene-responsive element (AP2/ERF) is a key transcription factor in plants that plays a vital role in regulating plant growth, development, and stress response. This study identified 202 AP2/ERF genes from the pecan genome and analyzed their distribution and duplication events. The analysis of gene structure and conserved motifs confirmed the conservation among AP2/ERF genes. Moreover, regulatory elements related to light responsiveness, stress, and defense responses were identified in the promoter regions of AP2/ERFs. Expression profiling of these genes during development and under abiotic stresses revealed the potential role of ERF-VII members in waterlogging stress. These findings provide insights into the evolution and divergence of AP2/ERF genes in pecan and have implications for further functional validation and stress-resistant variety development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Carmen Salguero-Aranda, Amparo Beltran-Povea, Fatima Postigo-Corrales, Ana Belen Hitos, Irene Diaz, Estefania Caballano-Infantes, Mario F. Fraga, Abdelkrim Hmadcha, Franz Martin, Bernat Soria, Rafael Tapia-Limonchi, Francisco J. Bedoya, Juan R. Tejedo, Gladys M. Cahuana
Summary: This study reveals that EGR-1 plays a negative role in regulating Pdx1 expression in mESCs, and its binding to the Pdx1 promoter depends on the methylation level and acetylation state of its DNA binding site. Targeting EGR-1 at early stages may be important for directing pluripotent cells towards Pdx1-dependent cell lineages.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Tao Liang, Jianbo Bai, Wei Zhou, Hao Lin, Shixin Ma, Xuechen Zhu, Qinghua Tao, Qiaoran Xi
Summary: This study reveals the transcriptional regulatory function of HMCES in the context of TGF-b family signaling. HMCES contributes to early development by maintaining nodal/activin- or BMP-signaling-regulated transcriptional network. HMCES competitively binds chromatin to limit binding by R-SMAD proteins, thereby repressing their regulatory effects.
Article
Biochemistry & Molecular Biology
Moritz Schaefer, Amena Nabih, Daniel Spies, Victoria Hermes, Maxime Bodak, Harry Wischnewski, Patrick Stalder, Richard Patryk Ngondo, Luz Angelica Liechti, Tatjana Sajic, Ruedi Aebersold, David Gatfield, Constance Ciaudo
Summary: Less than 10% of genes in mouse embryonic stem cells are directly regulated by miRNAs. Analysis of target genes of the stem cell-specific miR-290-295 cluster reveals TFAP4 as an important transcription factor for early development. The datasets developed in this study will support the improvement of predictive models for miRNA-mRNA functional interactions.
Article
Cell Biology
Zhangting Wang, Kai-Kei Miu, See-Wing Chan, Fanghong Ou, Patrick Wai-Nok Law, Wai-Yee Chan
Summary: In this study, scientists used an in vitro model to differentiate mouse embryonic stem cells and investigated the genome-wide distribution and impact of 5hmC during neuronal differentiation. They found that 5hmC was associated with gene activation and repression, and identified phosphatase and tensin homolog (Pten) as a key regulator for neuronal development. Additionally, thousands of differentially hydroxymethylated regions (DhMRs) were identified during differentiation, which were associated with neurogenesis and signal transduction. Combinational analysis also revealed Pten as a toggle to modulate mitochondrial associated pathways.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Engineering, Aerospace
Adam Hibberd, Nikolaos Perakis, Andreas M. Hein
Summary: The feasibility of sending a spacecraft to the second interstellar object 2I/Borisov using existing and near-term technologies has been assessed, showing that a Falcon Heavy launcher could have hauled an 8 ton spacecraft to 2I/Borisov in 2018. Using the Space Launch System (SLS), arrival at 2I/Borisov could be achieved in 2052. Additionally, earlier arrival times are possible with higher Delta V requirements and lower spacecraft payload masses.
Letter
Oncology
Manuel Sanclemente, Patricia Nieto, Sara Garcia-Alonso, Fernando Fernandez-Garcia, Laura Esteban-Burgos, Carmen Guerra, Matthias Drosten, Eduardo Caleiras, Jorge Martinez-Torrecuadrada, David Santamaria, Monica Musteanu, Mariano Barbacid
Article
Biochemistry & Molecular Biology
Antonio Galarreta, Pablo Valledor, Patricia Ubieto-Capella, Vanesa Lafarga, Eduardo Zarzuela, Javier Munoz, Marcos Malumbres, Emilio Lecona, Oscar Fernandez-Capetillo
Summary: Inhibitors of USP7 lead to widespread activation of CDK1 throughout the cell cycle, causing DNA damage and toxicity to mammalian cells. Additionally, USP7 interacts with the phosphatase PP2A, facilitating its active localization in the cytoplasm, and inhibition of USP7 or PP2A results in similar changes in the phosphoproteome, including increased phosphorylation of CDK1 targets.
Article
Multidisciplinary Sciences
Marina Salmon, Guillem Paniagua, Carmen G. Lechuga, Fernando Fernandez-Garcia, Eduardo Zarzuela, Ruth Alvarez-Diaz, Monica Musteanu, Carmen Guerra, Eduardo Caleiras, Javier Munoz, Sagrario Ortega, Matthias Drosten, Mariano Barbacid
Summary: In mice, the KRAS locus encodes two protein isoforms, KRAS4A and KRAS4B, differing only in their C terminus via alternative splicing of distinct fourth exons. By generating a mouse strain with a terminator codon in exon 4B, researchers created a bona fide Kras4B-null allele, leading to perinatal death due to heart defects. Lack of KRAS4B expression in mice resulted in reduced proliferation of fibroblasts but could be compensated for by ectopic expression of KRAS4A.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Alba Corman, Dimitris C. Kanellis, Patrycja Michalska, Maria Haggblad, Vanesa Lafarga, Jiri Bartek, Jordi Carreras-Puigvert, Oscar Fernandez-Capetillo
Summary: In this study, an image-based chemical screen was conducted to evaluate the effects of medically approved drugs and drugs under development on translation levels. The study found that certain compounds can reduce translation independently of mTOR, providing new insights for anticancer drug development.
Review
Oncology
Matthias Drosten, Mariano Barbacid
Summary: This article discusses the challenges of personalized medicine in treating KRAS mutant lung adenocarcinomas and highlights the recent breakthrough in developing selective KRAS(G12C) inhibitors. The mechanisms of resistance to these inhibitors and alternative therapeutic strategies to target KRAS oncogenic signaling are also explored. The article also examines the failure of MEK and ERK inhibitors in clinical trials and the potential of targeting RAF1 as a MAPK-independent activity. These developments are likely to provide new avenues for effectively treating KRAS mutant lung adenocarcinomas.
MOLECULAR ONCOLOGY
(2022)
Article
Oncology
Guillem Paniagua, Harrys K. C. Jacob, Oksana Brehey, Sara Garcia-Alonso, Carmen G. Lechuga, Tirso Pons, Monica Musteanu, Carmen Guerra, Matthias Drosten, Mariano Barbacid
Summary: KSR1 and KSR2 play important roles in the MAPK pathway, and overexpression of KSR1 or KSR2 can independently activate the pathway and induce cell proliferation. KSR1 requires dimerization with members of the RAF family to stimulate cell proliferation and decreases dependence on KRAS oncogenic signaling.
MOLECULAR ONCOLOGY
(2022)
Editorial Material
Oncology
Matilde Murga, Oscar Fernandez-Capetillo
Summary: These are exciting times to be involved in biomedical research, especially in the field of cancer drug discovery. The transition from scientific hypothesis to testable therapy is faster than ever, aided by the emergence of new technologies. This thematic issue provides an overview of recent advances and challenges in cancer drug development, offering a broad and updated perspective for those interested in developing cancer therapies.
MOLECULAR ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Alba Corman, Oleksandra Sirozh, Vanesa Lafarga, Oscar Fernandez-Capetillo
Summary: The nucleolus is where ribosome biogenesis takes place, which is one of the most resource-intensive processes in eukaryotic cells. It is highly responsive to growth signaling and nucleolar insults, collectively known as nucleolar stress. Nucleolar alterations are a prominent feature in various human diseases, including cancer and neurodegeneration, and are also associated with aging. There have been numerous efforts to develop compounds targeting different aspects of nucleolar activity. This article provides an overview of therapeutic opportunities and current therapies for targeting nucleoli in different pathologies.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Valeria Colicchia, Maria Haggblad, Oleksandra Sirozh, Bartlomiej Porebski, Mirela Balan, Xuexin Li, Louise Lidemalm, Jordi Carreras-Puigvert, Daniela Huhn, Oscar Fernandez-Capetillo
Summary: The tetR-regulated system was used to construct a human osteosarcoma cell line for inducible expression of TDP-43. Chemical screening with FDA-approved drugs identified compounds that prevented TDP-43 toxicity, but further experiments showed that these compounds inhibited doxycycline-dependent TDP-43 expression. A CRISPR/Cas9 screen revealed epigenetic regulators as potential modifiers of TDP-43 toxicity. However, G9a inhibition or TRIM28 loss also prevented doxycycline-dependent TDP-43 expression.
Editorial Material
Oncology
Matthias Drosten, Mariano Barbacid
Summary: This study identified a potent inhibitor for KRAS(G12D) and demonstrated its strong antitumor activity in preclinical models of pancreatic and colorectal cancer, especially when combined with other treatments.
MOLECULAR ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Jake A. Ward, Carles Perez-Lopez, Cristina Mayor-Ruiz
Summary: Degraders can induce the ubiquitination and degradation of disease-relevant proteins by targeting E3 ubiquitin ligases. This pharmacology offers a promising alternative to current therapeutic interventions and has the potential to broaden the range of targetable proteins. Biophysical and structural biology approaches are key in understanding degrader-induced ternary complex formation, and computational models are now being used to design new degraders. Effective crosstalk between experimental and computational strategies is crucial for advancements in the targeted protein degradation field.
Article
Medicine, Research & Experimental
Marina Salmon, Ruth Alvarez-Diaz, Coral Fustero-Torre, Oksana Brehey, Carmen G. Lechuga, Manuel Sanclemente, Fernando Fernandez-Garcia, Alejandra Lopez-Garcia, Maria Carmen Martin-Guijarro, Sandra Rodriguez-Perales, Emily Bousquet-Mur, Lucia Morales-Cacho, Francisca Mulero, Fatima Al-Shahrour, Lola Martinez, Orlando Dominguez, Eduardo Caleiras, Sagrario Ortega, Carmen Guerra, Monica Musteanu, Matthias Drosten, Mariano Barbacid
Summary: KRASG12C inhibitors have greatly improved the clinical management of KRASG12C-mutant lung adenocarcinoma patients, but resistance develops rapidly. In this study, genetically engineered mice were used to compare the efficacy and resistance between genetic ablation and pharmacological inhibition of mutant Kras. Results showed that Kras ablation effectively regressed tumors and prevented resistant cells, while treatment with sotorasib, a selective KRASG12C inhibitor, led to limited antitumor response and rapid onset of resistance. Unlike human tumors, resistance in mice was not due to mutations in RAS signaling pathways, but rather amplification of mutant Kras allele and activation of xenobiotic metabolism pathways.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Review
Chemistry, Multidisciplinary
Ana Domostegui, Luis Nieto-Barrado, Carles Perez-Lopez, Cristina Mayor-Ruiz
Summary: Protein-protein interactions (PPIs) are crucial for biological processes. Molecular glue degraders modulate PPIs by inducing protein proximity, thus overcoming limitations of traditional therapeutics and broadening the targetable proteome.
CHEMICAL SOCIETY REVIEWS
(2022)
Review
Biochemistry & Molecular Biology
Natalie S. Scholes, Cristina Mayor-Ruiz, Georg E. Winter
Summary: The therapeutic modality of targeted protein degradation offers a solution to the limitations of traditional pharmacology. Small-molecule degraders recruit disease-causing proteins to E3 ubiquitin ligases, leading to their ubiquitination and degradation. The integration of proteomics and functional genomics is crucial in identifying and understanding novel degraders and their mechanisms.
CELL CHEMICAL BIOLOGY
(2021)