Article
Cell Biology
Shoichiro Tani, Hiroyuki Okada, Shoko Onodera, Ryota Chijimatsu, Masahide Seki, Yutaka Suzuki, Xiaonan Xin, David W. Rowe, Taku Saito, Sakae Tanaka, Ung-il Chung, Shinsuke Ohba, Hironori Hojo
Summary: In this study, an integrative method was developed to model human skeletal development by inducing sclerotome from human pluripotent stem cells in vitro and forming endochondral bone in immunodeficient mice. The induced bones recapitulated the process of endochondral ossification and consisted of human skeletal cells and mouse circulatory cells. Single-cell multiome analysis revealed dynamic changes in chromatin accessibility and identified ZEB2 as a potential regulator of gene-regulatory networks in human osteogenesis. These findings provide insights into the molecular mechanisms of human skeletal development and offer a valuable research model.
Article
Biochemistry & Molecular Biology
Chiung-Fang Hsu, Kai-Chun Chang, Yi-Lan Chen, Po-Szu Hsieh, An- Lee, Jui-Yun Tu, Yu-Ting Chen, Jin-Der Wen
Summary: Programmed-1 ribosomal frameshifting in viruses and bacteria is stimulated by mRNA structures within the coding region. The RNA pseudoknot folds sequentially through upstream stem S1 and downstream stem S2, with S2 tending to be trapped in intermediates. Masking nucleotides can modulate mRNA refolding and facilitate the stable folding of native pseudoknots.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
M. G. R. Guastamacchia, R. Xue, K. Madi, W. T. E. Pitkeathly, P. D. Lee, S. E. D. Webb, S. H. Cartmell, P. A. Dalgarno
Summary: Multifocal microscopy (MUM) is a promising technique that can capture multiple fields of view from distinct axial planes simultaneously for micro-particle image velocimetry (mu PIV) with high accuracy. MUM can be applied to both fixed cells and live cells, showing significant advantages in speed of acquisition for mu PIV compared to standard confocal laser scanning microscope.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Masaru Mizukoshi, Masaru Kaku, Lay Thant, Kohei Kitami, Moe Arai, Isao Saito, Katsumi Uoshima
Summary: The study revealed that periodontal ligament (PDL) cells exhibit dynamic proliferative characteristics during orthodontic tooth movement-induced tissue remodeling, with proliferative cells likely undergoing further division and contributing to tissue remodeling. Additionally, proliferating cells expressed various molecular markers, indicating the lineage plasticity of PDL cells in vivo.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Aaron I. Weiner, Gan Zhao, Hanna M. Zayas, Nicolas P. Holcomb, Stephanie Adams-Tzivelekidis, Joanna Wong, Maria E. Gentile, Dyuthi Reddy, Joey Wei, Gargi Palashikar, Kwaku K. Quansah, Andrew E. Vaughan
Summary: The lung has a robust regenerative response to severe injuries, such as influenza infection, involving the proliferation and differentiation of lung epithelial cells and basal cells. The transcription factor ANp63 plays a critical role in regulating these reparative pathways, and loss of ANp63 leads to increased plasticity of basal cells and dysplastic tissue remodeling.
Article
Multidisciplinary Sciences
Saeed Farjami, Karen Camargo Sosa, Jonathan H. P. Dawes, Robert N. Kelsh, Andrea Rocco
Summary: The article presents biologically motivated mathematical models for cell differentiation that generate oscillations, providing alternative explanations to Waddington's epigenetic landscape. Two generic dynamical scenarios for describing the differentiation process are proposed, involving gradual variation of control parameters. Analyses on repressilator and its variants indicate that gene regulatory networks with repressilator-like characteristics may play a role in cell fate selection through oscillatory processes.
JOURNAL OF THE ROYAL SOCIETY INTERFACE
(2021)
Article
Biology
Kohei Saeki, Gregory Chang, Noriko Kanaya, Xiwei Wu, Jinhui Wang, Lauren Bernal, Desiree Ha, Susan L. Neuhausen, Shiuan Chen
Summary: The study presents an integrated mammary cell gene expression atlas derived from mouse and human single-cell RNA-sequence data, characterizing key life stages of mammary gland remodeling and inferring cells of origin for various breast cancer subtypes using breast cancer expression data.
COMMUNICATIONS BIOLOGY
(2021)
Review
Cell & Tissue Engineering
Lijun Wang, Xiuling You, Lingli Zhang, Changqing Zhang, Weiguo Zou
Summary: Bone remodeling is a lifelong process that involves a balance between bone formation and resorption. Mechanical forces play a crucial role in maintaining bone homeostasis, and loss of mechanical stimulation can weaken the bone structure and increase the risk of fracture. Understanding the mechanisms by which the body senses and transduces mechanical forces is important for studying bone disorders and developing strategies for skeletal rejuvenation.
Article
Cell Biology
Anna Maria Lena, Erica Foffi, Massimiliano Agostini, Mara Mancini, Margherita Annicchiarico-Petruzzelli, Daniel Aberdam, Tania Velletri, Yufang Shi, Gerry Melino, Ying Wang, Eleonora Candi
Summary: The transcription factor p53 plays a crucial role in controlling the differentiation process of mesenchymal stem cells. Other members of the p53 family, such as p63 and p73, may also be involved in this process. Specifically, TAp63 isoforms are shown to be upregulated during osteogenic differentiation, potentially impacting bone-related diseases and breast cancer metastasis.
Article
Biochemistry & Molecular Biology
Sunday Ndoma Bobori, Yuxiang Zhu, Alicia Saarinen, Alexis Josephine Liuzzo, Clifford D. L. Folmes
Summary: Growing evidence suggests that metabolites and energy metabolism have an active role in regulating cellular fate, particularly in cardiac development. A study on human pluripotent stem cells (PSCs) reveals significant metabolic remodeling during cardiac lineage specification, with most changes occurring during transitions from pluripotency to mesoderm and mesoderm to early cardiac stages. The findings highlight the opportunity to optimize metabolism during differentiation to support the specification and maturation of human PSC-derived cardiomyocytes.
Article
Cell & Tissue Engineering
Kyungtae Lim, Alex P. A. Donovan, Walfred Tang, Dawei Sun, Peng He, J. Patrick Pett, Sarah A. Teichmann, John C. Marioni, Kerstin B. Meyer, Andrea H. Brand, Emma L. Rawlins
Summary: Variation in lung alveolar development is linked to disease susceptibility. Researchers have identified an alveolar-fated epithelial progenitor in human fetal lungs and have grown them as self-organizing organoids to study cell lineage commitment. Using this system, they have discovered the role of Wnt signaling and the Wnt-NKX2.1 axis in alveolar differentiation, as well as the effects of genetic variation on this process.
Article
Biology
Qi Sun, Gehua Zhen, Tuo Peter Li, Qiaoyue Guo, Yusheng Li, Weiping Su, Peng Xue, Xiao Wang, Mei Wan, Yun Guan, Xinzhong Dong, Shaohua Li, Ming Cai, Xu Cao
Summary: The study demonstrates that intermittent parathyroid hormone can alleviate osteoarthritis pain through multiple mechanisms and may serve as a potential disease-modifying therapy for osteoarthritis.
Review
Cell Biology
Ying Ye, Xi Chen, Wensheng Zhang
Summary: Embryonic stem cells have a unique ability to maintain and regulate the balance between self-renewal and multi-lineage cellular differentiation, largely dependent on gene expression regulations. Chromatin remodeling complexes play a crucial role in promoting chromatin structural changes that ultimately affect ESC fate choices.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Erika Cosset, Youssef Hibaoui, Sten Ilmjarv, Pierre-Yves Dietrich, Caroline Tapparel, Karl-Heinz Krause
Summary: This study presents a standardized protocol for differentiating human embryonic stem cells into engineered neural tissue enriched with motor neurons, and highlights the role of motor neurons in poliovirus infection within these tissues. The research also reveals the molecular events occurring during PV-3 infection in the motor neurons and emphasizes the modulation of a set of genes involved in the EGR-EP300 complex.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Hematology
Oliver J. Herd, Gulab Fatima Rani, James P. Hewitson, Karen Hogg, Andrew P. Stone, Nichola Cooper, David G. Kent, Paul G. Genever, Ian S. Hitchcock
Summary: ITP progression drives significant expansion of progenitors and bone marrow remodeling in mice, while maintaining LT-HSC functionality through an adaptive BM microenvironment. This includes BM vasodilation, angiogenesis, and increased CXCL12 production, enabling improved progenitor homing to the BM. The changes in BM stromal cells are transient, but the vasculature alterations persist even after platelet count returns to normal.
Article
Cell Biology
Jing Luan, Guanjue Xiang, Pablo Aurelio Gomez-Garcia, Jacob M. Tome, Zhe Zhang, Marit W. Vermunt, Haoyue Zhang, Anran Huang, Cheryl A. Keller, Belinda M. Giardine, Yu Zhang, Yemin Lan, John T. Lis, Melike Lakadamyali, Ross C. Hardison, Gerd A. Blobel
Summary: CTCF, a conserved zinc finger transcription factor implicated in genome organization and transcription regulation, displays variable resistance to degradation at different binding sites. Motif sequence does not significantly predict degradation behavior, but location at chromatin boundaries and co-occupancy with cohesin are associated with delayed degradation. Single-molecule tracking experiments link chromatin residence time to CTCF degradation kinetics, providing insights into architectural CTCF functions.
Article
Biochemistry & Molecular Biology
Maria Victoria Neguembor, Laura Martin, Alvaro Castells-Garcia, Pablo Aurelio Gomez-Garcia, Chiara Vicario, Davide Carnevali, Jumana AlHaj Abed, Alba Granados, Ruben Sebastian-Perez, Francesco Sottile, Jerome Solon, Chao-ting Wu, Melike Lakadamyali, Maria Pia Cosma
Summary: The chromatin fiber forms loops through a scaffold structure of cohesin complexes, with RNA polymerase II located on the top of the loops. Increased loading of cohesin on chromosomes disrupts the nuclear rim and leads to chromatin blending, while altering supercoiling can counteract this blending phenomenon.
Article
Biochemistry & Molecular Biology
Alvaro Castells-Garcia, Ilyas Ed-Daoui, Esther Gonzalez-Almela, Chiara Vicario, Jason Ottestrom, Melike Lakadamyali, Maria Victoria Neguembor, Maria Pia Cosma
Summary: The study utilized super-resolution microscopy to visualize the nascent transcriptome in the nucleoplasm and nucleolus, revealing the organization of nascent RNAs into RNA nanodomains independent of transcript production. The research also demonstrated the physical relationship between nucleosome clutches, RNAP II, and RNA nanodomains, as well as the positioning of elongating RNAP II between nascent RNAs and transcriptionally active nucleosome clutches.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biology
Sarah G. Swygert, Dejun Lin, Stephanie Portillo-Ledesma, Po-Yen Lin, Dakota R. Hunt, Cheng-Fu Kao, Tamar Schlick, William S. Noble, Toshio Tsukiyama
Summary: The study found that an increase in the range of local inter-nucleosomal contacts in quiescent yeast drives genome-wide compaction of chromatin fibers, leading to global repression of transcription. Unlike actively dividing cells, inter-nucleosomal interactions in quiescent cells require a specific basic patch in the histone H4 tail.
Article
Medicine, General & Internal
Sergi Angel Bonilla-Pons, Shoma Nakagawa, Elena Garreta Bahima, Alvaro Fernandez-Blanco, Martina Pesaresi, Justin Christopher D'Antin, Ruben Sebastian-Perez, Daniela Greco, Eduardo Dominguez-Sala, Raul Gomez-Riera, Rafael Ignacio Barraquer Compte, Mara Dierssen, Nuria Montserrat Pulido, Maria Pia Cosma
Summary: This study discovered that cell fusion can occur between human müller glia and adult stem cells in the human retina, resulting in partial regeneration of neurons. The results suggest that cell fusion-mediated therapy may be a potential regenerative approach for treating human retinal dystrophies.
Article
Biochemistry & Molecular Biology
Maria Victoria Neguembor, Juan Pablo Arcon, Diana Buitrago, Rafael Lema, Jurgen Walther, Ximena Garate, Laura Martin, Pablo Romero, Jumana AlHaj Abed, Marta Gut, Julie Blanc, Melike Lakadamyali, Chao-ting Wu, Isabelle Brun Heath, Modesto Orozco, Pablo D. Dans, Maria Pia Cosma
Summary: The linear sequence of DNA provides important information about genes and their regulatory elements, but understanding gene function and regulation also requires knowledge of how genes fold in three-dimensional nuclear space. This study introduces immuno-OligoSTORM, an imaging strategy that allows super-resolution visualization of nucleosomes within specific genes by simultaneous visualization of DNA and histones. By combining immuno-OligoSTORM with modeling approaches, the method called Modeling immuno-OligoSTORM enables quantitative modeling of genes at nucleosome resolution and provides information about chromatin accessibility for regulatory factors.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Serena F. Generoso, Maria Victoria Neguembor, Elliot A. Hershberg, Ruslan I. Sadreyev, Kazuki Kurimoto, Yukihiro Yabuta, Raffaele Ricci, Pauline Audergon, Moritz Bauer, Mitinori Saitou, Konrad Hochedlinger, Brian J. Beliveau, Maria Pia Cosma, Jeannie T. Lee, Bernhard Payer
Summary: Reactivation of the inactive X chromosome is a key event during reprogramming, and the cohesin complex member SMC1a plays a crucial role in this process. Depletion of SMC1a affects X chromosome reactivation without interfering with iPSC-reprogramming, and it is necessary for the decompacted state of the active X chromosome. Our findings highlight the importance of cohesin in the remodeling of the X chromosome and its critical role in iPSC-reprogramming.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Cell Biology
Maria Pia Cosma, Maria Victoria Neguembor
Summary: Technological breakthroughs in super-resolution microscopy have allowed researchers to explore the three-dimensional folding of chromatin and its relationship with genome function. By combining imaging and genomic approaches, new insights and challenges in genome architecture have been revealed. The review discusses the achievements, challenges, and future directions in understanding genome folding, emphasizing the contributions of super-resolution microscopy and live-cell imaging.
Article
Biology
Hayley Porter, Yang Li, Maria Victoria Neguembor, Manuel Beltran, Wazeer Varsally, Laura Martin, Manuel Tavares Cornejo, Dubravka Pezic, Amandeep Bhamra, Silvia Surinova, Richard G. Jenner, Maria Pia Cosma, Suzana Hadjur
Summary: This study reveals the important role of Stromalin Antigen (SA) proteins in the localization and loading of the cohesin complex. The findings demonstrate that SA proteins interact with RNA, RNA binding proteins, and R-loops, independently of cohesin. These results provide new insights into the relationship between cohesin loading and chromatin structure.
Article
Biochemistry & Molecular Biology
Laura Martin, Maria Victoria Neguembor, Maria Pia Cosma
Summary: One of the biggest paradoxes in biology is the disparity in size between the human genome and the nucleus that contains it. Despite being approximately 2 meters long, the DNA must be compacted and accessible for replication and transcription. The role of DNA torsional stress as a regulator of chromatin compaction and accessibility is discussed, with a focus on the influence of topoisomerases on genome organization.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Cell Biology
Marie Christou-Kent, Sergi Cuartero, Carla Garcia-Cabau, Julia Ruehle, Julian Naderi, Julia Erber, Maria Victoria Neguembor, Marcos Plana-Carmona, Marc Alcoverro-Bertran, Luisa De Andres-Aguayo, Antonios Klonizakis, Eric Julia-Vilella, Cian Lynch, Manuel Serrano, Denes Hnisz, Xavier Salvatella, Thomas Graf, Gregoire Stik
Summary: The transcription factor CEBPA plays a role in cell identity by influencing genome architecture. It can undergo phase separation through its intrinsically disordered region, leading to the formation of specific nuclear foci and regulation of gene function.