Focus 26 January 2021

From molecules and cells to organisms

Living things are a complex, coordinated network of systems, and understanding their basic organization and function integrates multiple levels of biology. This page broadly highlights our most exciting recent publications covering topics from molecular mechanisms of cellular behaviours to organismal physiology.

Featured articles

Defects in placental syncytiotrophoblast cells are a common cause of developmental heart disease

Placental dysfunction can affect heart development, but the prevalence of this causality has not been well established. Here, the authors use mouse genetic tools to show that the placenta may constitute a significant source of congenital heart defects.
- Bethany N. Radford
- Xiang Zhao
- Myriam Hemberger
ArticleOpen Access1 Mar 2023 Nature Communications
Growth anisotropy of the extracellular matrix shapes a developing organ

Tissue morphogenesis is a complex process that involves tissue growth, mechanics, and shape changes. This work demonstrates that differences in growth rate and direction between a tissue layer and its associated extracellular matrix drive 3D shape changes during organ growth.
- Stefan Harmansa
- Alexander Erlich
- Thomas Lecuit
ArticleOpen Access3 Mar 2023 Nature Communications
IDH3γ functions as a redox switch regulating mitochondrial energy metabolism and contractility in the heart

Protein targets that are affected by ROS and underly impaired inotropic effects in the heart are largely unknown. Here, the authors identify the γ-subunit of IDH3 as a redox switch linking oxidative stress to impaired metabolism and heart function.
- Maithily S. Nanadikar
- Ana M. Vergel Leon
- Dörthe M. Katschinski
ArticleOpen Access14 Apr 2023 Nature Communications
Muscle cell-type diversification is driven by bHLH transcription factor expansion and extensive effector gene duplications

Different muscle cell types account for specific abilities in animals, yet how their diversification arose remains unclear. Here, the authors show that gene duplications of bHLH transcription factors and effector genes contributed to the diversification of muscle cell types in the sea anemone Nematostella.
- Alison G. Cole
- Stefan M. Jahnel
- Ulrich Technau
ArticleOpen Access29 Mar 2023 Nature Communications
A defect in mitochondrial protein translation influences mitonuclear communication in the heart

The heart requires high levels of mitochondria to sustain function, and mitochondrial stressors can be transmitted to the nucleus and reprogram metabolism. Here, the authors show that a mitochondrial ribosomal protein is important for heart development in mice by increasing nuclear Klf15 expression.
- Feng Gao
- Tian Liang
- Jinghai Chen
ArticleOpen Access22 Mar 2023 Nature Communications
Defective BVES-mediated feedback control of cAMP in muscular dystrophy

cAMP is an important second messenger involved in many aspects of biological processes. Here, Li et al. shows that blood vessel epicardial substance (BVES) is a negative regulator of cAMP signaling required for maintaining muscle mass and function.
- Haiwen Li
- Peipei Wang
- Renzhi Han
ArticleOpen Access30 Mar 2023 Nature Communications
Emergent collective organization of bone cells in complex curvature fields

It remains unclear how cells respond to complex extracellular geometries at the mesoscale. Here, the authors study the organization of bone cells in landscapes with varying curvatures, observing a preference for local concavities, multicellular bridging, and collective stress fiber orientation.
- Sebastien J. P. Callens
- Daniel Fan
- Amir A. Zadpoor
ArticleOpen Access3 Mar 2023 Nature Communications
TRAK adaptors regulate the recruitment and activation of dynein and kinesin in mitochondrial transport

The mechanisms of microtubule-based mitochondrial transport remain poorly understood. Here, the authors show that the mitochondrial TRAK adaptors activate the dynein-dynactin complex, enhance the motility of kinesin, and can scaffold both motors to control bidirectional transport.
- John T. Canty
- Andrew Hensley
- Ahmet Yildiz
ArticleOpen Access13 Mar 2023 Nature Communications
Temporal-iCLIP captures co-transcriptional RNA-protein interactions

Dynamic RNA-protein interactions govern the co-transcriptional packaging of RNA polymerase II derived transcripts. Here the authors use temporal-iCLIP which combines transcriptional synchronisation with UV cross-linking of RNA-protein complexes to reveal dynamic RNA-protein interactions during the early phases of transcription and beyond.
- Ross A. Cordiner
- Yuhui Dou
- Torben Heick Jensen
ArticleOpen Access8 Feb 2023 Nature Communications
De novo lipogenesis fuels adipocyte autophagosome and lysosome membrane dynamics

The function of de novo lipogenesis (DNL) in adipocytes has been a mystery as it contributes little to fat storage in these cells. Here, the authors show that DNL is a critical source of fatty acids for membrane-expanding processes like autophagy.
- Leslie A. Rowland
- Adilson Guilherme
- Michael P. Czech
ArticleOpen Access13 Mar 2023 Nature Communications
Light-driven biological actuators to probe the rheology of 3D microtissues

The mechanical properties of biological tissues are key to their integrity and function. Here, the authors engineer 3D microtissues from optogenetically modified fibroblasts and use light to quantify tissue elasticity and strain propagation using their own constituent cells as internal actuators.
- Adrien Méry
- Artur Ruppel
- Thomas Boudou
ArticleOpen Access9 Feb 2023 Nature Communications
The p97-UBXD8 complex regulates ER-Mitochondria contact sites by altering membrane lipid saturation and composition

Inter-organellar contacts are hubs for several critical cellular processes, such as lipid synthesis. Here Ganji et al. show that the p97-UBXD8 complex modulates contacts by regulating membrane lipid composition and saturation.
- Rakesh Ganji
- Joao A. Paulo
- Malavika Raman
ArticleOpen Access6 Feb 2023 Nature Communications
Adaptive partitioning of a gene locus to the nuclear envelope in Saccharomyces cerevisiae is driven by polymer-polymer phase separation

Partitioning of active genes to the nuclear periphery is commonly observed but not understood. Here, the authors show that this process occurs by phase separation of transcriptionally active chromatin providing for efficient mRNA transport and memory.
- Lidice González
- Daniel Kolbin
- Stephen W. Michnick
ArticleOpen Access28 Feb 2023 Nature Communications
Homeotic compartment curvature and tension control spatiotemporal folding dynamics

Morphogenetic shape changes are regulated by mechanical properties of interacting tissues, but other factors remain less studied. By exploring how homeotic genes regulate morphogenesis, Villedieu et al. uncover how the interplay between genetic patterning and initial tissue geometry drives morphogenesis during development.
- Aurélien Villedieu
- Lale Alpar
- Yohanns Bellaïche
ArticleOpen Access3 Feb 2023 Nature Communications
Single-cell atavism reveals an ancient mechanism of cell type diversification in a sea anemone

Understanding how new cell types arise is essential for understanding the evolution of animal diversity. This study shows that a single gene, NvSox2, acts as a simple switch controlling the development of two alternative types of stinging cells in the sea anemone Nematostella vectensis.
- Leslie S. Babonis
- Camille Enjolras
- Mark Q. Martindale
ArticleOpen Access16 Feb 2023 Nature Communications
Sex-specificity of the C. elegans metabolome

Biological sex affects all aspects of animal physiology. Using the model C. elegans, the authors show that metabolomes are highly sex-specific and include a vast space of yet unidentified metabolites that may control development and lifespan.
- Russell N. Burkhardt
- Alexander B. Artyukhin
- Frank C. Schroeder
ArticleOpen Access19 Jan 2023 Nature Communications
In vivo clonal tracking reveals evidence of haemangioblast and haematomesoblast contribution to yolk sac haematopoiesis

The lineage relationship between blood and endothelial cells has been difficult to examine due to the multiphasic timing of hematopoiesis in the embryo. Here the authors use using in vivo barcoding technology to assess cell ancestry and show that blood and endothelial cells emerge through common (haemangioblast) or separate (mesenchymoangioblasts and haematomesoblasts) progenitors in the yolk sac.
- C. Biben
- T. S. Weber
- S. Taoudi
ArticleOpen Access3 Jan 2023 Nature Communications
The lipid flippase SLC47A1 blocks metabolic vulnerability to ferroptosis

Ferroptosis is cell death caused by lipid peroxidation and plasma membrane rupture. Here, the authors report an additional role for the lipid flippase SLC47A1 as a regulator of lipid remodeling and survival during ferroptosis, thereby providing a metabolic target for overcoming drug resistance.
- Zhi Lin
- Jiao Liu
- Minghua Yang
ArticleOpen Access27 Dec 2022 Nature Communications
Intracellular galectin-3 is a lipopolysaccharide sensor that promotes glycolysis through mTORC1 activation

The carbohydrate binding protein galectin-3 has been linked to diabetes and cancer. Here, authors show that galectin-3 is a sensor of LPS, an important modulator of the mTORC1 signaling, and a critical regulator of glucose metabolism.
- Xing Chen
- Chunyu Yu
- Yongfeng Shang
ArticleOpen Access8 Dec 2022 Nature Communications
Slowest possible replicative life at frigid temperatures for yeast

It is unclear what constraints exist on cellular life in frigid environments. Here, the authors demonstrate that reactive oxygen species and gene-expression speed impose a barrier to replication at low temperatures in yeast, with lower levels enabling quicker replication, and develop a model to describe this phenomenon.
- Diederik S. Laman Trip
- Théo Maire
- Hyun Youk
ArticleOpen Access6 Dec 2022 Nature Communications
Feedback between mechanosensitive signaling and active forces governs endothelial junction integrity

Gap formation in the vasculature underpins immune and tumour cell infiltration. Here the authors propose a chemo-mechanical model to analyse how feedback between mechanosensitive signalling, active cellular forces and adhesion governs the breakdown, recovery, and integrity of endothelial junctions.
- Eoin McEvoy
- Tal Sneh
- Vivek B. Shenoy
ArticleOpen Access19 Nov 2022 Nature Communications
Dominant ARF3 variants disrupt Golgi integrity and cause a neurodevelopmental disorder recapitulated in zebrafish

Disruptions to the ER-Golgi network can lead to neurodevelopmental disorders, though our understanding of these Golgipathies remains incomplete. Here Lauri, Tartaglia and colleagues show that ARF3 mutations cause a rare pediatric neurological disorder and perform detailed molecular characterization in fish.
- Giulia Fasano
- Valentina Muto
- Marco Tartaglia
ArticleOpen Access11 Nov 2022 Nature Communications
CHD7 regulates otic lineage specification and hair cell differentiation in human inner ear organoids

Mutations in the chromatin remodeler CHD7 cause CHARGE syndrome, affecting development of several organs including the inner ear. Here, the authors recapitulated pathogenesis of this disease with human inner ear organoids and found that CHD7 is indispensable for proper otic lineage specification and hair cell differentiation.
- Jing Nie
- Yoshitomo Ueda
- Eri Hashino
ArticleOpen Access17 Nov 2022 Nature Communications
DOT1L regulates chamber-specific transcriptional networks during cardiogenesis and mediates postnatal cell cycle withdrawal

How and whether histone modifications regulate distinct gene networks remains insufficiently understood. Here Cattaneo et al show that DOT1L catalyzed H3K79me2 regulates fetal chamber-specific gene expression and neonatal cardiomyocyte cell cycle withdrawal to coordinate heart development.
- Paola Cattaneo
- Michael G. B. Hayes
- Sylvia M. Evans
ArticleOpen Access2 Dec 2022 Nature Communications
Nuclear localization of mitochondrial TCA cycle enzymes modulates pluripotency via histone acetylation

Cellular metabolism is important in pluripotency and cell fate regulation. Here, authors observe chromatin remodeling followed by TCA enzyme translocation from the mitochondria to the nucleus, demonstrating pluripotency regulation by mitochondria to nucleus retrograde signaling.
- Wei Li
- Qi Long
- Xingguo Liu
ArticleOpen Access2 Dec 2022 Nature Communications
Differential nuclear import sets the timing of protein access to the embryonic genome

Here the authors address how embryos control the timing of specific gene activation in early frog development. They find transcription factors for early gene activation are maternally loaded and remain at constant levels, and rather that order of activation is based on their sequential entry into the nucleus based largely on their respective affinity to importins.
- Thao Nguyen
- Eli J. Costa
- Martin Wühr
ArticleOpen Access6 Oct 2022 Nature Communications
On-microscope staging of live cells reveals changes in the dynamics of transcriptional bursting during differentiation

Here the authors observe transcription dynamics in real-time throughout erythropoiesis by combining PP7 tagging of α-globin RNA transcripts and “on-microscope” cell staging. They show how the pattern of transcriptional bursting changes during differentiation, with variability in individual cells significantly reduced at the peak period of gene expression.
- D. M. Jeziorska
- E. A. J. Tunnacliffe
- D. R. Higgs
ArticleOpen Access4 Nov 2022 Nature Communications
Programmable integrin and N-cadherin adhesive interactions modulate mechanosensing of mesenchymal stem cells by cofilin phosphorylation

Human mesenchymal stem cells differentiate in response to mechanical adhesive interactions in their microenvironment. Here, the authors develop a culture platform that can dynamically mimic the cell-cell and cell-extracellular matrix interactions associated with development and mesenchymal differentiation in vivo.
- Zheng Zhang
- Baoyong Sha
- Min Lin
ArticleOpen Access11 Nov 2022 Nature Communications
Sphingosine 1-phosphate mediates adiponectin receptor signaling essential for lipid homeostasis and embryogenesis

Cells and organisms requires proper membrane composition, which the cell must modulate as membrane lipids are primary acquired from the diet. Here, Ruiz et al. identify a conserved pathway connecting the fluidity regulators AdipoR1/2 with fatty acid desaturase SCD to mediate membrane homeostasis.
- Mario Ruiz
- Ranjan Devkota
- Marc Pilon
ArticleOpen Access22 Nov 2022 Nature Communications
Spatially resolved phosphoproteomics reveals fibroblast growth factor receptor recycling-driven regulation of autophagy and survival

Recruitment of Receptor Tyrosine Kinase signalling partners during endocytosis, specifically during recycling to the plasma membrane, is crucial to signal propagation and regulation. Here, the authors reveal FGFR signalling partners proximal to recycling endosomes with a spatially resolved phosphoproteomics approach.
- Joanne Watson
- Harriet R. Ferguson
- Chiara Francavilla
ArticleOpen Access3 Nov 2022 Nature Communications
The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision

Motile and non-motile cilia have distinct functions and protein complexes associated with them. Here, the authors show the conserved protein CFAP20 is important for both motile and non-motile cilia and is distinct from other ciliopathy-associated domains or macromolecular complexes.
- Paul W. Chrystal
- Nils J. Lambacher
- Michel R. Leroux
ArticleOpen Access3 Nov 2022 Nature Communications
Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells

Chronic hyperglycemia impairs insulin secretion from pancreatic beta cells in diabetes. Here, the authors reveal that a glucose metabolite is responsible and show lowering glucose metabolism during hyperglycemia prevents loss of beta-cell function.
- Elizabeth Haythorne
- Matthew Lloyd
- Frances M. Ashcroft
ArticleOpen Access14 Nov 2022 Nature Communications
A noncanonical function of EIF4E limits ALDH1B1 activity and increases susceptibility to ferroptosis

Ferroptosis is lipid peroxidation-dependent cell death that has potential to be harnessed as a cancer therapeutic. Here, the authors show that the translation initiation factor eIF4E can repress ALDH1B1 independent of translation, increasing lipid peroxidation levels to promote ferroptosis.
- Xin Chen
- Jun Huang
- Rui Kang
ArticleOpen Access23 Oct 2022 Nature Communications
L-threonine promotes healthspan by expediting ferritin-dependent ferroptosis inhibition in C. elegans

How dietary restriction increases longevity is still not fully understood. Here, the authors demonstrate that L-threonine is an essential mediator of dietary restriction that prevents age-induced ferroptosis and that dietary supplementation promotes healthy ageing.
- Juewon Kim
- Yunju Jo
- Dongryeol Ryu
ArticleOpen Access2 Nov 2022 Nature Communications
A conserved megaprotein-based molecular bridge critical for lipid trafficking and cold resilience

Environmental temperature changes can alter cell membrane lipid composition but the mechanisms underlying this conserved mechanism are unclear. Here, the authors identify the megaprotein LPD-3 in C. elegans as critical for normal phospholipid distribution and cold resilience.
- Changnan Wang
- Bingying Wang
- Dengke K. Ma
ArticleOpen Access10 Nov 2022 Nature Communications
Single-molecule tracking of Nodal and Lefty in live zebrafish embryos supports hindered diffusion model

Multiple models have been proposed for how diffusion is regulated to shape morphogen gradients. Here they use single molecule tracking of an activator-inhibitor signaling pair in a developing tissue to show how effective diffusivity is modulated in the extracellular space.
- Timo Kuhn
- Amit N. Landge
- J. Christof M. Gebhardt
ArticleOpen Access15 Oct 2022 Nature Communications
Actin polymerization promotes invagination of flat clathrin-coated lattices in mammalian cells by pushing at lattice edges

The role of actin filaments in clathrin-mediated endocytosis (CME) is unclear. Here, Yang et al. show that branched actin filaments promote CME by pushing on clathrin coat edges in an epsin-dependent manner, dividing large flat clathrin plaques into sizes that facilitate invagination.
- Changsong Yang
- Patricia Colosi
- Tatyana Svitkina
ArticleOpen Access17 Oct 2022 Nature Communications
Live imaging and conditional disruption of native PCP activity using endogenously tagged zebrafish sfGFP-Vangl2

Planar cell polarity (PCP) is critical for tissue-wide coordination and successful development. Here Jussila et al. generate a GFP-Vangl2 fusion for live imaging and discover a surprising directionality to the intercellular propagation of cell polarity, and ultimately link PCP defects with idiopathic scoliosis.
- Maria Jussila
- Curtis W. Boswell
- Brian Ciruna
ArticleOpen Access23 Sep 2022 Nature Communications
PIM1 promotes hepatic conversion by suppressing reprogramming-induced ferroptosis and cell cycle arrest

Protein kinase-mediated phosphorylation plays a critical role in many biological processes. Here the authors develop a trans-omics-based algorithm called Central Kinase Inference to integrate quantitative transcriptomic and phosphoproteomic data, finding that PIM1 promotes hepatic conversion by suppressing reprogramming-induced ferroptosis and cell cycle arrest.
- Yangyang Yuan
- Chenwei Wang
- Pengyu Huang
ArticleOpen Access6 Sep 2022 Nature Communications
MRTF specifies a muscle-like contractile module in Porifera

Myocytes are a key cell type that enable animal movement, but their evolutionary origins remain unclear. Colgren and Nichols describe molecular and functional similarities between a contractile module in tissues of a sponge and muscle tissues in other animals, indicating a common evolutionary origin.
- J. Colgren
- S. A. Nichols
ArticleOpen Access15 Jul 2022 Nature Communications
GCAF(TMEM251) regulates lysosome biogenesis by activating the mannose-6-phosphate pathway

Lysosomal biogenesis errors often result in diseases including mucolipidosis. Here Zhang and Yang et al. identify TMEM251/GCAF as a mannose-6-phosphate modification regulator that is necessary for correct lysosomal targeting, and classify Mucolipidosis Type V as resulting from GCAF mutations.
- Weichao Zhang
- Xi Yang
- Ming Li
ArticleOpen Access12 Sep 2022 Nature Communications
TRIM24 is an insulin-responsive regulator of P-bodies

Insulin promotes hepatic lipogenesis, though underlying regulation remains unclear. Here the authors show that insulin translocates TRIM24 from the nucleus into cytosolic P-bodies to stabilise hepatic Pparγ mRNA, and that inactivation of TRIM24 promotes Pparγ degradation and alleviates hepatosteatosis.
- Wen Wei
- Qiaoli Chen
- Shuai Chen
ArticleOpen Access8 Jul 2022 Nature Communications
Evidence for a HURP/EB free mixed-nucleotide zone in kinetochore-microtubules

Microtubules are built from GDP-tubulin lattices with small GTP caps at their plus-ends. Here, the authors reveal that microtubules that attach to kinetochores in mitosis contain, in addition to the GTP-cap and the GDP-lattices, a dynamic micron-sized mixed-nucleotide zone.
- Cédric Castrogiovanni
- Alessio V. Inchingolo
- Patrick Meraldi
ArticleOpen Access10 Aug 2022 Nature Communications
Global stable-isotope tracing metabolomics reveals system-wide metabolic alternations in aging Drosophila

Stable-isotope tracing allows quantifying metabolic activity by measuring isotopically labeled metabolites, but its metabolome coverage has been limited. Here, the authors develop a global isotope tracing approach with metabolome-wide coverage and use it to characterize metabolic activities in aging Drosophila.
- Ruohong Wang
- Yandong Yin
- Zheng-Jiang Zhu
ArticleOpen Access20 Jun 2022 Nature Communications
DDX1 vesicles control calcium-dependent mitochondrial activity in mouse embryos

The DEAD box protein DDX1 is known to form large aggregates in the cytoplasm of early mouse embryos. Here the authors identify DDX1-containing vesicles and show that loss of Ddx1 affects their integrity, compromising mitochondria function and causing embryonic lethality.
- Yixiong Wang
- Lubna Yasmin
- Roseline Godbout
ArticleOpen Access1 Jul 2022 Nature Communications
Endothelial cell heterogeneity and microglia regulons revealed by a pig cell landscape at single-cell level

Pigs are important large animal models for biomedical research. Here, the authors construct a single-cell landscape of pig tissues, unravelling the phenotypic heterogeneity of blood endothelial cells in adipose tissues and the evolutionally conserved regulons of microglia in brains.
- Fei Wang
- Peiwen Ding
- Yonglun Luo
ArticleOpen Access24 Jun 2022 Nature Communications
Elasticity of podosome actin networks produces nanonewton protrusive forces

Actin filaments generate force in diverse contexts, although how they can produce nanonewtons of force is unclear. Here, the authors apply cryo-electron tomography, quantitative analysis, and modelling to reveal the podosome core is a dense, spring-loaded, actin network storing elastic energy.
- Marion Jasnin
- Jordan Hervy
- Renaud Poincloux
ArticleOpen Access4 Jul 2022 Nature Communications
Adipocyte HIF2α functions as a thermostat via PKA Cα regulation in beige adipocytes

Thermogenic adipocytes maintain body temperature in response to cold, but how this is tuned during cold and re-warming is unclear. Here, the authors show HIF2α inhibits beige adipocyte retention, regulating PKA catalysis to control dynamic adipocyte remodelling.
- Ji Seul Han
- Yong Geun Jeon
- Jae Bum Kim
ArticleOpen Access7 Jun 2022 Nature Communications
Membrane curvature regulates the spatial distribution of bulky glycoproteins

MUC1 is a heavily glycosylated protein on the cell surface. Here the authors show that MUC1 prefers negative over positive membrane curvature due to its bulky size, enabling MUC1 to avoid endocytosis and surface removal based on curvature preference.
- Chih-Hao Lu
- Kayvon Pedram
- Bianxiao Cui
ArticleOpen Access2 Jun 2022 Nature Communications
Stress-induced protein disaggregation in the endoplasmic reticulum catalysed by BiP

Aggregation of misfolded proteins underlie dementias. Here, the authors show that stressed cells activate an innate mechanism to resolve aggregates of defective proteins in the endoplasmic reticulum, where a third of cellular proteins are produced.
- Eduardo Pinho Melo
- Tasuku Konno
- Edward Avezov
ArticleOpen Access6 May 2022 Nature Communications

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