Cell growth

  • Article
    | Open Access

    DNA:RNA hybrids (R-loops) are products of transcription that impact genome integrity and gene expression. Here the authors reveal a mechanism for regulating R-loops in a ubiquitination-dependent manner controlled by the activities of USP11 and KEAP1

    • Mateusz Jurga
    • , Arwa A. Abugable
    •  & Sherif F. El-Khamisy
  • Article
    | Open Access

    Inability to image large numbers of growth plate chondrocytes while retaining their spatial context during analysis has hindered the study of bone development. Here, the authors present a pipeline called 3D MAPs and use it to uncover morphogenic behaviors and growth strategies in normal bones as well as  aberrations in Gdf5 KO bones.

    • Sarah Rubin
    • , Ankit Agrawal
    •  & Elazar Zelzer
  • Article
    | Open Access

    Dynamic cell wall assembly is key to cell shape maintenance during bacterial growth. Here, the authors present a method that allows high-resolution analysis of active and inert zones of cell wall growth during bacterial elongation. They also formulate a mathematical model to predict the partitioning of cell wall-anchored proteins following cell division.

    • Yi-Jen Sun
    • , Fan Bai
    •  & Chien-Jung Lo
  • Article
    | Open Access

    Bacterial cells actively change their size and shape in response to external environments. Here, Shi et al. explore how cells regulate their morphology during rapid environmental changes, showing that the characteristic dynamics of surface area-to-volume ratio are conserved across genetic and chemical perturbations, as well as across species and growth temperatures.

    • Handuo Shi
    • , Yan Hu
    •  & Kerwyn Casey Huang
  • Article
    | Open Access

    The pandemic of COVID-19, caused by SARS-CoV-2 infection, warrants immediate investigation for therapy options. Here the authors show, using epithelial and air-liquid interface cultures, that SARS-CoV-2 hijacks host cell metabolism to facilitate viral replication, and that inhibition of mTORC1, a master metabolic regulator, suppresses viral replication.

    • Peter J. Mullen
    • , Gustavo Garcia Jr
    •  & Heather R. Christofk
  • Article
    | Open Access

    ASXL1 mutations are frequently found in age-related clonal haemaotopoiesis (CH), but how they drive CH is unclear. Here the authors show that expression of C-terminal truncated ASXL1 in haematopoietic stem cells (HSCs) leads to Akt de-ubiquitination, activated Akt/mTOR signaling, and aberrant HSC proliferation.

    • Takeshi Fujino
    • , Susumu Goyama
    •  & Toshio Kitamura
  • Article
    | Open Access

    Interorganelle membrane contact sites between the endoplasmic reticulum and mitochondria can be mediated with the ER-mitochondria encounter structure (ERMES) complex, though precise regulation is unclear. Here, the authors report that the number of ERMES foci is regulated by the previously uncharacterized mitochondrial membrane protein Emr1.

    • Faiz Rasul
    • , Fan Zheng
    •  & Chuanhai Fu
  • Article
    | Open Access

    While cell shape is crucial for function and development of organisms, versatile frameworks for cell shape quantification, comparison, and classification remain underdeveloped. Here, the authors use a network-based framework for Arabidopsis leaf epidermal cell shape characterization and classification.

    • Jacqueline Nowak
    • , Ryan Christopher Eng
    •  & Zoran Nikoloski
  • Article
    | Open Access

    Tuberous sclerosis complex (TSC) regulates cell growth by controlling the activity of mTORC1. The structure of human TSC complex reveals an arch-shaped, asymmetric architecture and a 2:2:1 stoichiometry of TSC1, TSC2, and TBC1D7 subunits and suggests a mechanism by which TSC2 accelerates GTP hydrolysis against a small GTPase Rheb.

    • Huirong Yang
    • , Zishuo Yu
    •  & Yanhui Xu
  • Article
    | Open Access

    Quantitative phase imaging suffers from a lack of specificity in label-free imaging. Here, the authors introduce Phase Imaging with Computational Specificity (PICS), a method that combines phase imaging with machine learning techniques to provide specificity in unlabeled live cells with automatic training.

    • Mikhail E. Kandel
    • , Yuchen R. He
    •  & Gabriel Popescu
  • Article
    | Open Access

    Cell proliferation is regulated by cell volume, but it is unclear how individual cancer cells coordinate to regulate cell volumes in 3D clusters. Here the authors propose a mechano-osmotic model to analyse the exchange of fluid and ions between connected cells and their environment in response to proliferation-induced solid stress.

    • Eoin McEvoy
    • , Yu Long Han
    •  & Vivek B. Shenoy
  • Article
    | Open Access

    Targeting the interaction between transcription factor TEAD and its co-repressor VGL4 is an attractive strategy to chemically modulate Hippo signaling. Here, the authors develop a proteomimetic with stabilized tertiary structure that inhibits the TEAD:VGL4 interaction in vitro and in cells.

    • Hélène Adihou
    • , Ranganath Gopalakrishnan
    •  & Herbert Waldmann
  • Article
    | Open Access

    Autophagy is important during stress and development, but how the metabolites generated are used by the cell remains unclear. Here, the authors demonstrate that budding yeast require autophagy to provide serine for one-carbon metabolism during the switch from glycolytic to respiratory growth.

    • Alexander I. May
    • , Mark Prescott
    •  & Yoshinori Ohsumi
  • Article
    | Open Access

    Energy metabolism and ATP levels are controlled by an interlocking network of pathways. Here, the authors apply a genome-wide CRISPR screen to define genes that increase or decrease ATP levels to define the “ATPome”, a map of pathways that contribute to cellular ATP regulation.

    • Neal K. Bennett
    • , Mai K. Nguyen
    •  & Ken Nakamura
  • Article
    | Open Access

    Bacteria can form wall-deficient variants, or L-forms, that divide by a simple mechanism that does not require the FtsZ-based cell division machinery. Here, Wu et al. study L-forms in microfluidic systems to show the importance of geometric effects for cell growth, chromosome segregation and cell division.

    • Ling Juan Wu
    • , Seoungjun Lee
    •  & Jeff Errington
  • Article
    | Open Access

    3D liver organoids hold great promise for regenerative medicine but the use of ill-defined matrices limits their potential. Here, the authors generate human and mouse liver organoids using a chemically defined matrix, and reveal a link between matrix stiffness and organoid growth that does not require acto-myosin contraction.

    • Giovanni Sorrentino
    • , Saba Rezakhani
    •  & Kristina Schoonjans
  • Article
    | Open Access

    Budding yeast cell polarization is known to self-assemble, but it is still not clear what controls the size of the resulting septin ring. Here the authors show that the septin ring diameter is set by cell volume, ensuring that larger cells have larger rings.

    • I. V. Kukhtevich
    • , N. Lohrberg
    •  & K. M. Schmoller
  • Article
    | Open Access

    Hippo TEAD-transcriptional regulators YAP1 and TAZ modulate cell growth, but the downstream networks are unclear. Here, the authors use a genetically-encoded inhibitor of YAP1/TAZ interaction with TEAD (TEADi) to disrupt transcriptional networks for cell cycle and terminal differentiation in human keratinocytes and mouse skin.

    • Yao Yuan
    • , Jeannie Park
    •  & Ramiro Iglesias-Bartolome
  • Article
    | Open Access

    Mycobacteria grow by inserting new cell wall material at the cell poles. Here, Hannebelle et al. combine time-lapse optical and atomic force microscopy to show that single-cell growth is biphasic due to a lag phase of variable duration before the new pole transitions from slow to fast growth.

    • Mélanie T. M. Hannebelle
    • , Joëlle X. Y. Ven
    •  & Georg E. Fantner
  • Article
    | Open Access

    Macropinocytosis has been implicated in the expansion of transformed cells when nutrient-depleted. Here the authors show that macropinocytosis also contributes to the expansion of primary T cells even under nutrient-replete conditions, potentially by providing access of extracellular amino acids to an endolysosomal compartment to sustain mTORC1 activation.

    • John C. Charpentier
    • , Di Chen
    •  & Philip D. King
  • Article
    | Open Access

    Natural killer/T cell lymphoma (NKTCL) is a rare and aggressive disease. Here, the authors identify recurrent somatic mutations of GNAQ in NKTCL, and model how this mutation contributes to NKTCL pathogenesis.

    • Zhaoming Li
    • , Xudong Zhang
    •  & Mingzhi Zhang
  • Article
    | Open Access

    Oncogene induced senescence protects cells from unrestricted growth and cancer. Here, the authors show that PAK4 overrides this senescence in breast cancer cells through phosphorylation of RELB, thereby inhibiting transcription of the senescence regulator C/EBPβ.

    • Tânia D. F. Costa
    • , Ting Zhuang
    •  & Staffan Strömblad
  • Article
    | Open Access

    It is unclear how circuit specificity and function are maintained during organismal growth. In this study, authors show that connectivity between primary nociceptors and their downstream neurons scales with animal size and that Ste20-like kinase Tao acts as a negative regulator of synaptic growth required for maintenance of circuit specificity and connectivity.

    • Federico Marcello Tenedini
    • , Maria Sáez González
    •  & Peter Soba
  • Article
    | Open Access

    Animals can adapt their body size to changing environments (e.g., temperature) but the underlying molecular mechanisms are unknown. Here, the authors show that temperature and the genetic factors insulin-like peptide receptor and FoxO determine size in Hydra via the conserved pathways (Wnt/TGF-β).

    • Benedikt M. Mortzfeld
    • , Jan Taubenheim
    •  & Thomas C. G. Bosch
  • Article
    | Open Access

    The hypoxia response pathway couples oxygen availability to physiological adaptations. Using the model system Drosophila melanogaster, here the authors show that hypoxia inhibits TORC1 signalling and increases lipid levels in the larval fat body and that these effects are required for development to adulthood.

    • Byoungchun Lee
    • , Elizabeth C. Barretto
    •  & Savraj S. Grewal
  • Article
    | Open Access

    Insulin signaling represses Forkhead transcription factor FoxO activity, which contributes to organismal metabolism. Here, the authors use proteomics to identify positively regulated insulin signaling targets FoxK1/K2 and demonstrate their role in lipid metabolism and mitochondrial regulation.

    • Masaji Sakaguchi
    • , Weikang Cai
    •  & C. Ronald Kahn
  • Article
    | Open Access

    Hippo pathway inactivation plays a role in many cancers, although how tumor cells depress signaling is unclear. Here, Lim et al. identify STK25, which activates LATS in a manner distinct from other upstream kinases and is focally deleted from a range of human cancers.

    • Sanghee Lim
    • , Nicole Hermance
    •  & Neil J. Ganem
  • Article
    | Open Access

    The phosphatase Shp-2 was implicated in NK cell education due to its reported association with inhibitory receptors, but its function in this context is unclear. Here the authors show that Shp-2 is not required for NK cell function, but is necessary for IL-15-induced metabolic burst and expansion.

    • Charlène Niogret
    • , S. M. Shahjahan Miah
    •  & Greta Guarda
  • Article
    | Open Access

    It is unclear whether a constrictive force is exerted on the membrane from inside during bacterial cell division, or cell wall remodeling alone drives membrane constriction from outside. Here, the authors use simulations to explore different mechanisms for cell wall division, supporting that a constrictive force is required.

    • Lam T. Nguyen
    • , Catherine M. Oikonomou
    •  & Grant J. Jensen
  • Article
    | Open Access

    Hippo signaling leads to the phosphorylation of the key transcriptional effector, Yap/Yki, although how Yap/Yki stability is regulated has remained unclear. Here, Sun et al. identify HAUSP/Usp7 as a conserved and clinically relevant regulator of the Hippo pathway that increases Yap/Yki stability.

    • Xiaohan Sun
    • , Yan Ding
    •  & Zizhang Zhou
  • Article
    | Open Access

    Cortical microtubules of Toxoplasma gondii are exceptionally stable, but it isn’t known how they are anchored along membranes. Here, Harding et al. show that GAPM proteins localize to the inner membrane complex and are essential for maintaining the structural stability of parasites.

    • Clare R. Harding
    • , Matthew Gow
    •  & Sebastian Lourido
  • Article
    | Open Access

    Most tumours are characterized by increased aerobic glycolytic activity. Here the authors show that elevated  aerobic glycolysis is not essential for cancer initiation by testing the effect of lactate dehydrogenase depletion on the ability of hair follicle stem cells (HFSCs) to form squamous cell carcinoma (SCC) in mouse genetic models.

    • A. Flores
    • , S. Sandoval-Gonzalez
    •  & W. E. Lowry
  • Article
    | Open Access

    The PI3K/Akt/mTOR pathway has been previously implicated in fibrosis and a pan-PI3K/mTOR inhibitor is currently under clinical evaluation for the treatment of IPF. Here the authors show that the mTORC1/4E-BP1 axis is critical for TGF-β1-induced fibrogenesis in in vitro and ex vivo models and that canonical PI3K/Akt signalling is dispensable.

    • Hannah V. Woodcock
    • , Jessica D. Eley
    •  & Rachel C. Chambers
  • Article
    | Open Access

    Increased levels of the Yap oncoprotein stimulate liver growth and promote hepatocarcinogenesis. Here the authors show that hepatocyte-specific loss of Atg7 in mice leads to decreased autophagic degradation of Yap and liver overgrowth, and further establish this association in human liver cancer tissues.

    • Youngmin A. Lee
    • , Luke A. Noon
    •  & Scott L. Friedman
  • Article
    | Open Access

    The transcriptional co-factors Yap and TAZ are regulated by Hippo signalling and mechanical forces via their nucleocytoplasmic shuttling. Here the authors identify a RhoA-regulated C-terminal nuclear localization signal and a TEAD-regulated N-terminal nuclear export signal of TAZ in an epithelial cell line.

    • Michael Kofler
    • , Pam Speight
    •  & András Kapus
  • Article
    | Open Access

    Hippo-YAP pathway plays an important role in cancers; however the in vivo relevance of YAP/TAZ target genes is unclear. Here, the authors show that NUAK2 is a target of YAP and participates in a feedback loop to maximize YAP activity. Inhibition of NUAK2 suppresses YAP-driven hepatomegaly and liver cancer growth, offering a new target for cancer therapy.

    • Wei-Chien Yuan
    • , Brian Pepe-Mooney
    •  & Fernando D. Camargo
  • Article
    | Open Access

    The drivers of growth rate variability in bacteria are yet unknown. Here, the authors present a theory to predict the growth dynamics of individual cells and use a stochastic cell model integrating metabolism, gene expression and replication to identify the processes that underlie growth variation.

    • Philipp Thomas
    • , Guillaume Terradot
    •  & Andrea Y. Weiße
  • Article
    | Open Access

    During mammary gland involution, the organ undergoes extensive remodeling. Here, the authors explore the role of mammary gland adipose tissue (mgWAT) in this process and demonstrate that adipocyte hypertrophy and lipid trafficking underlie mgWAT expansion and epithelial regression.

    • Rachel K. Zwick
    • , Michael C. Rudolph
    •  & Valerie Horsley
  • Article
    | Open Access

    The size of cells fluctuates but there are limited experimental methods to measure live mammalian cell sizes. Here, the authors track single cell volume (FXm) over the cell cycle and generate a mathematical framework to compare size homeostasis in datasets ranging from bacteria to mammalian cells.

    • Clotilde Cadart
    • , Sylvain Monnier
    •  & Matthieu Piel