Featured
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Comment |
Bringing computation to biology by bridging the last mile
Advances in technology dramatically accelerate biology research, with computation being a standout example. Typically, adapting a new technology follows stages from method creation, via proof-of-concept application to biology, to the development of usable tools. Creating user-friendly software to bridge computer science and biology is a crucial step, yielding high returns on investment and driving biological discoveries. However, we need dedicated resources and a shift in the academic reward system to harness the full potential of computer science in biology.
- Anne E. Carpenter
- & Shantanu Singh
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Article
| Open AccessSingle-cell spatial multi-omics and deep learning dissect enhancer-driven gene regulatory networks in liver zonation
Bravo González-Blas et al. uncover enhancer-gene regulatory networks underlying hepatocyte identity and their zonation state by combining single-cell and spatial multiomics with massively parallel reporter assays and deep learning.
- Carmen Bravo González-Blas
- , Irina Matetovici
- & Stein Aerts
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Technical Report
| Open AccessJoint epigenome profiling reveals cell-type-specific gene regulatory programmes in human cortical organoids
Noack and Vangelisti et al. present 3DRAM-seq, which simultaneously profiles genome organization, chromatin accessibility and DNA methylation at high resolution and allows mapping cell-type-specific epigenetic regulation in human neurogenesis.
- Florian Noack
- , Silvia Vangelisti
- & Boyan Bonev
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Resource |
An atlas of rabbit development as a model for single-cell comparative genomics
Ton, Keitley et al. provide a morphological and molecular atlas of rabbit development. Comparative studies reveal that combining rabbit and mouse atlases can serve as a model for dissecting early primate development.
- Mai-Linh Nu Ton
- , Daniel Keitley
- & Berthold Göttgens
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Article
| Open AccessAn mRNA processing pathway suppresses metastasis by governing translational control from the nucleus
Using ribosome profiling, Navickas et al. show that heterogeneous nuclear ribonucleoprotein C functions with PABPC4 to regulate alternative polyadenylation of a set of mRNAs, which inhibits lung metastasis in xenograft models of breast cancer.
- Albertas Navickas
- , Hosseinali Asgharian
- & Hani Goodarzi
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Technical Report
| Open AccessBiologically informed deep learning to query gene programs in single-cell atlases
Lotfollahi et al. present ExpiMap, a deep-learning model enabling interpretable reference mapping of RNA sequencing data using biologically defined entities, offering end-to-end analysis from dataset integration to functional interpretation.
- Mohammad Lotfollahi
- , Sergei Rybakov
- & Fabian J. Theis
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Article |
KCNQ1OT1 promotes genome-wide transposon repression by guiding RNA–DNA triplexes and HP1 binding
Zhang et al. report that the long noncoding RNA KCNQ1OT1 binds to double-stranded genomic DNA and to the heterochromatin protein HP1α to induce and maintain epigenetic silencing at repetitive DNA elements and guard against genomic instability and senescence.
- Xiaoli Zhang
- , Quanlong Jiang
- & Jing-Dong J. Han
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Article
| Open AccessPan-cancer pervasive upregulation of 3′ UTR splicing drives tumourigenesis
Chan et al. report that 3′ UTR splicing is widespread and enhanced across different cancer types and is associated with more advanced tumour progression.
- Jia Jia Chan
- , Bin Zhang
- & Yvonne Tay
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Article |
ETV2 functions as a pioneer factor to regulate and reprogram the endothelial lineage
Gong et al. report that ETV2 functions as a pioneer factor that remodels chromatin and regulates endothelial genes, thus providing a mechanism of endothelial development with potential therapeutic applications.
- Wuming Gong
- , Satyabrata Das
- & Daniel J. Garry
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Article |
The PPR domain of mitochondrial RNA polymerase is an exoribonuclease required for mtDNA replication in Drosophila melanogaster
Liu et al. report that Drosophila melanogaster mitochondrial RNA polymerase harbours an intrinsic 3′-to-5′ exoribonuclease activity that enables it to generate short RNA primers for mitochondrial DNA replication.
- Yi Liu
- , Zhe Chen
- & Hong Xu
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Technical Report |
CellComm infers cellular crosstalk that drives haematopoietic stem and progenitor cell development
Lummertz da Rocha et al. present CellComm, an algorithm that analyses cell–cell communication to predict signalling and regulatory networks, and identify regulators of haematopoietic development in the aorta–gonad–mesonephros region.
- Edroaldo Lummertz da Rocha
- , Caroline Kubaczka
- & George Q. Daley
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Perspective |
Exploring the expanding universe of small RNAs
Shi et al. discuss recent approaches for the discovery of small noncoding RNAs (sncRNAs), limitations associated with sncRNA expression analyses, and emerging methods for direct and simultaneous detection of multiple RNA modifications.
- Junchao Shi
- , Tong Zhou
- & Qi Chen
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Perspective |
Cell type ontologies of the Human Cell Atlas
In this Perspective, Teichmann and colleagues present ongoing efforts from consortia of the Human Cell Atlas to harmonize and integrate data sources into a reference cell ontology and the contributions of cell ontologies to discovery.
- David Osumi-Sutherland
- , Chuan Xu
- & Sarah A. Teichmann
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Perspective |
Anatomical structures, cell types and biomarkers of the Human Reference Atlas
In this Perspective, Börner et al. discuss initiatives by 16 consortia to construct a Human Reference Atlas (HRA) comprising reference organs linked to tables that name major anatomical structures, cell types, plus biomarkers (ASCT+B) and present examples of HRA usage.
- Katy Börner
- , Sarah A. Teichmann
- & Griffin Weber
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Article |
Dynamic transcriptional reprogramming leads to immunotherapeutic vulnerabilities in myeloma
Frede et al. perform single-cell transcriptome and chromatin accessibility profiling of immune cells isolated from patients with refractory multiple myeloma before or during the course of chemotherapy.
- Julia Frede
- , Praveen Anand
- & Jens G. Lohr
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Letter |
Non-canonical Wnt/PCP signalling regulates intestinal stem cell lineage priming towards enteroendocrine and Paneth cell fates
Polarity cues regulate intestinal stem cell fate. Böttcher et al. demonstrate that mouse intestinal stem cells, which express the Wnt/planar cell polarity reporter Flattop, are primed either towards the enteroendocrine or Paneth cell lineage.
- Anika Böttcher
- , Maren Büttner
- & Heiko Lickert
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News & Views |
A bridge between melanoma cell states
Cellular plasticity allows tumours to adapt to and overcome therapeutic challenges. A recent study uncovered the gene regulatory networks that govern cell states and phenotype switching in melanoma, opening up possibilities to therapeutically target cell states or phenotypic plasticity to render melanoma cells more vulnerable to treatment.
- Nicole M. Aiello-Couzo
- & Yibin Kang
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Article |
Robust gene expression programs underlie recurrent cell states and phenotype switching in melanoma
Profiling phenotype switching in melanoma. Wouters et al. perform large-scale gene expression analysis in patient samples and identify transcriptional networks that modulate the intermediate cell state and ultimate mesenchymal switching in melanoma.
- Jasper Wouters
- , Zeynep Kalender-Atak
- & Stein Aerts
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News & Views |
In and out from senescence
Cellular senescence has been widely recognised for decades as a stable arrest of cell proliferation. A recent study identifies senescence establishment and maintenance as a dynamic and reversible process regulated by (in)activation of a predetermined enhancer landscape controlled by the pioneer transcription factor AP-1.
- Sara Zumerle
- & Andrea Alimonti
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Article |
AP-1 imprints a reversible transcriptional programme of senescent cells
Bischof and colleagues report that AP-1 bookmarks prospective senescence enhancers for future activation to achieve a timely execution of the senescence programme.
- Ricardo Iván Martínez-Zamudio
- , Pierre-François Roux
- & Oliver Bischof
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News & Views |
Unraveling bone marrow architecture
Different types of stromal cells in the bone marrow associate to form niches that support differentiating blood cells and ensure lifelong production of all major blood lineages. A study now combines single-cell and spatial transcriptomics with imaging to infer the cellular composition and spatial architecture of specific niches.
- Daniel Lucas
- , Nathan Salomonis
- & H. Leighton Grimes
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Resource |
Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms
Using a BioID approach, Bagci et al. systematically analyse the Rho-family GTPase interactome and reveal previously unappreciated interactions with RhoGEFs and RhoGAPs and effectors for Rho proteins.
- Halil Bagci
- , Neera Sriskandarajah
- & Jean-François Côté
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Article |
Combined single-cell and spatial transcriptomics reveal the molecular, cellular and spatial bone marrow niche organization
Baccin, Al-Sabah, Velten et al. use single-cell and spatially resolved transcriptomics to map the cellular, molecular and spatial organization of the endosteal, sinusoidal and arteriolar bone marrow niches.
- Chiara Baccin
- , Jude Al-Sabah
- & Simon Haas
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Article |
Early chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineages
Ling and Sauka-Spengler reveal chromatin and transcriptional landscapes that regulate the early specification of vagal neural crest cells during the development of the enteric nervous system in chicken.
- Irving T. C. Ling
- & Tatjana Sauka-Spengler
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Letter |
miRNA-mediated feedback inhibition of JAK/STAT morphogen signalling establishes a cell fate threshold
Unpaired morphogen specifies migratory border-cell migration in a STAT-dependent manner, so that cells with low STAT signalling do not migrate. In a feedback loop, miR-279 generates a cell-fate threshold in STAT signalling in response to the Upd gradient to prevent inappropriate migration.
- Wan Hee Yoon
- , Hans Meinhardt
- & Denise J. Montell
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Editorial |
Protocol Exchange
Protocol Exchange, a new online repository to enable sharing of protocols.
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Comment |
Finding an image in a haystack: the case for public image repositories
Image repositories are growing. Their potential impact is huge; they require support and proper funding.
- Jason R. Swedlow
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Article |
Endothelial cells dynamically compete for the tip cell position during angiogenic sprouting
Notch and vascular endothelial growth factor receptor (VEGFR) coordinates endothelial cells behaviour during angiogenesis sprouting although exactly how is uncertain. Endothelial cells dynamically compete for the leading position in a sprout through relative levels of Vegfr1 and Vegfr2 in a Notch dependent manner.
- Lars Jakobsson
- , Claudio A. Franco
- & Holger Gerhardt
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