Featured
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| Open AccessNANOG initiates epiblast fate through the coordination of pluripotency genes expression
Pluripotent epiblast cells segregate from primitive endoderm in the blastocyst inner cell mass (ICM). Here the authors show that mosaic epiblast differentiation during mouse and human preimplantation development initiates stochastically in ICM progenitors, independently of the FGF pathway, and requires NANOG activity
- Nicolas Allègre
- , Sabine Chauveau
- & Claire Chazaud
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Article
| Open AccessRobust temporal map of human in vitro myelopoiesis using single-cell genomics
The myeloid lineage is central to homeostasis and immunity. The authors provide an atlas of human iPSC-to-myeloid cell differentiation and demonstrate that the in vitro system recapitulates yolk sac differentiation, opening new avenues to human myelopoiesis.
- Clara Alsinet
- , Maria Nascimento Primo
- & Roser Vento-Tormo
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| Open AccessA conserved YAP/Notch/REST network controls the neuroendocrine cell fate in the lungs
Notch signaling is known to control neuroendocrine fate in the lungs. Shue and colleagues further identify the REST and YAP transcriptional regulators as key components of the Notch signaling pathway in the control of the neuroendocrine cell fate in lung development, lung injury response, and small-cell lung cancer.
- Yan Ting Shue
- , Alexandros P. Drainas
- & Julien Sage
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| Open AccessReduced chromatin accessibility correlates with resistance to Notch activation
Notch signalling plays a key role in cell fate transitions, but how Notch activates distinct regulatory networks in closely related cell types is not well understood. Here the authors profile Notch and RBPJ targets in the developing mouse cortex and reveal how transcription factor occupancy and chromatin remodelling interact to direct differential gene expression during differentiation.
- Jelle van den Ameele
- , Robert Krautz
- & Andrea H. Brand
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Article
| Open AccessTranscription factors AP-2α and AP-2β regulate distinct segments of the distal nephron in the mammalian kidney
How the distal nephron is patterned during kidney development has been difficult to study. Here they show that AP-2β is required for the formation and postnatal function of distal convoluted tubules, whereas AP-2α has a role in maintaining the structure of medullary collecting ducts.
- Joseph O. Lamontagne
- , Hui Zhang
- & Alexander G. Marneros
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Article
| Open AccessVasa nucleates asymmetric translation along the mitotic spindle during unequal cell divisions
Association of mRNA translation with the mitotic spindle is thought to be involved in localized production of cell fate determinants. Here, the authors show Vasa facilitates asymmetric translation, which contributes to differential regulation during sea urchin embryogenesis.
- Ana Fernandez-Nicolas
- , Alicia Uchida
- & Mamiko Yajima
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Article
| Open AccessCell-intrinsic Aryl Hydrocarbon Receptor signalling is required for the resolution of injury-induced colonic stem cells
Rapid intestinal regeneration after injury is critical to maintain barrier integrity and homeostasis, but must be tightly controlled to prevent tumorigenesis. Here they show that the aryl hydrocarbon receptor is required to terminate the regenerative response after wound healing.
- Kathleen Shah
- , Muralidhara Rao Maradana
- & Brigitta Stockinger
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Article
| Open AccessHand2 delineates mesothelium progenitors and is reactivated in mesothelioma
The mesothelium supports homeostasis and regeneration, yet its development origins remain unclear. Here, the authors uncovered the earliest mesothelium progenitor cells in zebrafish, linking Hand2 gene function to mesothelium formation and its re-activation to mesothelioma tumors.
- Karin D. Prummel
- , Helena L. Crowell
- & Christian Mosimann
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Article
| Open AccessMassively parallel reporter perturbation assays uncover temporal regulatory architecture during neural differentiation
How gene regulatory elements regulate gene expression during cellular differentiation remains largely unknown. Here the authors use perturbation-based massively parallel reporter assays at early time points of neural differentiation to systematically characterize how regulatory elements and motifs within them guide different transcriptional patterns.
- Anat Kreimer
- , Tal Ashuach
- & Nadav Ahituv
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Article
| Open AccessCD4 expression in effector T cells depends on DNA demethylation over a developmentally established stimulus-responsive element
Epigenetic states that are established during thymic T cell development influence functionality of mature T cells. Authors here show that early developmental programming of the Cd4 locus is comprised of DNA-demethylation at a specific stimulus-responsive element, which allows long-term maintenance of activator histone H3K4 trimethylation and transcription.
- Athmane Teghanemt
- , Priyanjali Pulipati
- & Priya D. Issuree
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Article
| Open AccessConstitutive activation of canonical Wnt signaling disrupts choroid plexus epithelial fate
The cerebrospinal fluid-secreting choroid plexus needs a balanced level of canonical Wnt signaling. Here the authors show that if this signaling is over-activated, the choroid plexus loses its properties and function, and transforms to a neuronal identity.
- Arpan Parichha
- , Varun Suresh
- & Shubha Tole
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Article
| Open AccessIntegration of single-cell transcriptomes and chromatin landscapes reveals regulatory programs driving pharyngeal organ development
The molecular basis and gene regulatory networks driving pharyngeal endoderm development remain poorly understood. Here the authors report single cell transcriptomic and chromatin landscapes to delineate regulatory programs driving this process and to define the immunodeficiency-associated developmental defects resulting from Foxn1 dysfunction.
- Margaret E. Magaletta
- , Macrina Lobo
- & René Maehr
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| Open AccessExpression of the transcription factor PU.1 induces the generation of microglia-like cells in human cortical organoids
The study of human microglia function in health and disease is limited by the availability of sound models. Here, the authors develop a method to generate functional microglia in human cortical organoids and investigate the role of human microglia during amyloid beta1-42- induced inflammation.
- Bilal Cakir
- , Yoshiaki Tanaka
- & In-Hyun Park
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Article
| Open AccessMyoD is a 3D genome structure organizer for muscle cell identity
Pioneer transcription factors (TFs) have been proposed to act as protein anchors to orchestrate cell type-specific 3D genome architecture. MyoD is a pioneer TF for myogenic lineage specification. Here the authors provide further support for the role of MyoD in 3D genome architecture in muscle stem cells by comparing MyoD knockout and wild-type mice.
- Ruiting Wang
- , Fengling Chen
- & Dahai Zhu
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| Open AccessRobust differentiation of human enteroendocrine cells from intestinal stem cells
Hormone-producing enteroendocrine cells (EEC) regulate of energy homeostasis and gastrointestinal function. Here the authors report protocols to induce human intestinal stem cells into EECs producing multiple gut hormones, including SST, 5-HT, CCK and GIP, using directed differentiation with small molecules targeting FOXO1, JNK and CB1 signalling.
- Daniel Zeve
- , Eric Stas
- & David T. Breault
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Article
| Open AccessLifelong single-cell profiling of cranial neural crest diversification in zebrafish
Cranial neural crest generates a wide diversity of cell types. Here the authors perform single-cell profiling of neural crest to identify key enhancers and transcription factors for cell fate competency, thus revealing progressive acquisition of fate potential.
- Peter Fabian
- , Kuo-Chang Tseng
- & J. Gage Crump
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Article
| Open AccessVviPLATZ1 is a major factor that controls female flower morphology determination in grapevine
Unlike wild Vitis species, which produce either female or male flowers, modern grapevine cultivars form hermaphrodite flowers for self-pollination. Here, the authors report that the VviPLATZ1 (plant AT-rich sequence-and zinc-binding protein1) transcription factor functions in controlling female flower morphology determination.
- Pat Iocco-Corena
- , Jamila Chaïb
- & Harley M. Smith
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| Open AccessProgenitor translatome changes coordinated by Tsc1 increase perception of Wnt signals to end nephrogenesis
The cessation of nephrogenesis determines nephron endowments in mammals. Here the authors show that differential translation of Wnt antagonists versus agonists determines the tipping point from self-renewal to differentiation of nephron progenitors during nephrogenesis, using mutant mice with elevated nephron numbers.
- Alison E. Jarmas
- , Eric W. Brunskill
- & Raphael Kopan
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| Open AccessInner nuclear protein Matrin-3 coordinates cell differentiation by stabilizing chromatin architecture
Interactions between chromatin and nuclear components and whether these interactions affect development is not well understood. Here the authors show inner nuclear protein Matrin-3 (Matr3) loss leads to accelerated erythroid maturation, and that Matr3 is involved in chromosomal structure organization and compartmentalization to negatively regulate cell differentiation.
- Hye Ji Cha
- , Özgün Uyan
- & Stuart H. Orkin
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Article
| Open AccessMicrotubule-based transport is essential to distribute RNA and nascent protein in skeletal muscle
It is increasingly recognised that the spatial localisation of RNA is important for proper cellular function. Here, the authors investigate RNA localisation in skeletal muscle and develop methods to show that global active transport of RNA is required to maintain dispersion of gene products in the large muscle syncytium.
- Lance T. Denes
- , Chase P. Kelley
- & Eric T. Wang
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| Open AccessDissecting transition cells from single-cell transcriptome data through multiscale stochastic dynamics
How to infer transient cells and cell-fate transitions from snap-shot single cell transcriptome dataset remains a major challenge. Here the authors present a multiscale approach to construct single-cell dynamical manifold, quantify cell stability, and compute transition trajectory and probability between cell states.
- Peijie Zhou
- , Shuxiong Wang
- & Qing Nie
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| Open AccessSingle-cell transcriptomic analysis of bloodstream Trypanosoma brucei reconstructs cell cycle progression and developmental quorum sensing
Trypanosoma brucei undergoes developmental steps during host infection. Here, using oligopeptide-induced differentiation in vitro, authors model replicative ‘slender’ to transmissible ‘stumpy’ bloodstream forms and identify developmental and cell cycle regulators by single cell transcriptomics.
- Emma M. Briggs
- , Federico Rojas
- & Thomas D. Otto
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| Open AccessSelf-assembling human heart organoids for the modeling of cardiac development and congenital heart disease
There is a pressing need to develop representative organ-like platforms recapitulating complex in vivo phenotypes to study human development and disease in vitro. Here the authors present a method to generate human heart organoids by self-assembly using pluripotent stem cells, compare these to age-matched fetal cardiac tissues and recreate a model of pregestational diabetes.
- Yonatan R. Lewis-Israeli
- , Aaron H. Wasserman
- & Aitor Aguirre
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| Open AccessGrafting of iPS cell-derived tenocytes promotes motor function recovery after Achilles tendon rupture
Tendon self-renewal occurs rarely and reconstructive surgery comes with significant limitations. Here the authors present an induced pluripotent stem cell-based method to generate tenocytes, analyze their developmental trajectory using scRNA-seq, and demonstrate their contribution to motor function recovery after Achilles tendon injury via engraftment and paracrine effects.
- Taiki Nakajima
- , Akihiro Nakahata
- & Makoto Ikeya
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| Open AccessHuman iPS-derived pre-epicardial cells direct cardiomyocyte aggregation expansion and organization in vitro
The authors form pre-epicardial cells (PECs) from hiPSC-derived lateral plate mesoderm on treating with BMP4, RA and VEGF, and co-culture these PECs with cardiomyocytes, inducing cardiomyocyte aggregation, proliferation and network formation with more mature structures and improved beating/contractility.
- Jun Jie Tan
- , Jacques P. Guyette
- & Harald C. Ott
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Article
| Open AccessLineageOT is a unified framework for lineage tracing and trajectory inference
Lineage tracing and snapshots of transcriptional state at the single-cell level are powerful, complementary tools for studying development. Here, the authors propose a mathematical method combining lineage tracing with trajectory inference to improve our understanding of development.
- Aden Forrow
- & Geoffrey Schiebinger
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Article
| Open AccessCRISPR/Cas9-engineered inducible gametocyte producer lines as a valuable tool for Plasmodium falciparum malaria transmission research
During each replication cycle of P. falciparum in the human bloodstream, a small proportion of parasites commits to sexual development and differentiates into transmission-relevant gametocytes. Applying CRISPR-based genome editing, Boltryk et al. engineer P. falciparum lines with sexual commitment rates of 75% to promote future studies on gametocyte biology.
- Sylwia D. Boltryk
- , Armin Passecker
- & Till S. Voss
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Article
| Open AccessVertically transferred maternal immune cells promote neonatal immunity against early life infections
Maternal immune cells seed into the foetus during mammalian pregnancy, yet the functional role of these cells is unclear. Here the authors show that maternal immune cells in foetal bone marrow stimulate immune development, subsequently reducing the risk or severity of infections in newborns.
- Ina Annelies Stelzer
- , Christopher Urbschat
- & Petra Clara Arck
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| Open AccessMassively parallel in vivo CRISPR screening identifies RNF20/40 as epigenetic regulators of cardiomyocyte maturation
Throughput of in vivo genetic screens is a barrier to efficient application. Here the authors use a high-throughput CRISPR-based in vivo forward genetic screen in mice to identify transcriptional regulators of cardiomyocyte maturation, including the epigenetic modifiers RNF20 and RNF40.
- Nathan J. VanDusen
- , Julianna Y. Lee
- & William T. Pu
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Article
| Open AccessTranscriptional profiling of mESC-derived tendon and fibrocartilage cell fate switch
The transcriptional regulators underlying the induction and differentiation of dense connective tissues remain largely unknown. Here the authors generate tendon and fibrocartilage cells from mouse embryonic stem cells and apply scRNA-seq to identify molecular regulation of the cell fate switch between these lineages.
- Deepak A. Kaji
- , Angela M. Montero
- & Alice H. Huang
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Article
| Open AccessFibroblast fusion to the muscle fiber regulates myotendinous junction formation
Classically, myogenic precursor cells derive from somites, and connective tissues derive from lateral plate mesoderm (LPM). Here the authors identify LPM derived fibroblasts that turn on a myogenic program and fuse to muscle fibers at muscle-tendon junctions, introducing fibroblast transcripts into myofibers.
- Wesal Yaseen
- , Ortal Kraft-Sheleg
- & Peleg Hasson
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| Open AccessUnexpected contribution of fibroblasts to muscle lineage as a mechanism for limb muscle patterning
The dogma is that limb muscle cells originate from somite, while connective tissue fibroblasts derive from lateral plate mesoderm. Here the authors identify a fibroblast population that undergoes myoblast conversion in response to BMP and contributes nuclei to myotubes at the myotendinous junction.
- Joana Esteves de Lima
- , Cédrine Blavet
- & Delphine Duprez
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| Open AccessChemical combinations potentiate human pluripotent stem cell-derived 3D pancreatic progenitor clusters toward functional β cells
Human pluripotent stem cell (hPSC) derived pancreatic beta cells are a promising and potentially limitless source for cell replacement therapy. Here the authors perform stage-wise chemical screening to develop an improved protocol for hPSC differentiation to functional pancreatic beta cells at high efficiency.
- Haisong Liu
- , Ronghui Li
- & Juan Carlos Izpisua Belmonte
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| Open AccessGeneration of functional liver organoids on combining hepatocytes and cholangiocytes with hepatobiliary connections ex vivo
Combining mouse hepatocyte progenitors and cholangiocytes ex vivo, the authors form an organoid that can drain bile ex vivo and transport metabolites, as in the liver.
- Naoki Tanimizu
- , Norihisa Ichinohe
- & Toshihiro Mitaka
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| Open AccessReinforcing one-carbon metabolism via folic acid/Folr1 promotes β-cell differentiation
Regeneration of insulin-producing beta-cells may become a future alternative treatment of diabetes. Here the authors report a genetic screen in a zebrafish model that mimics the loss of beta-cells in diabetes, and identified that the folate receptor Folr1 or folinic acid treatment can stimulate beta-cell regeneration.
- Christos Karampelias
- , Habib Rezanejad
- & Olov Andersson
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Article
| Open AccessGenerative modeling of single-cell time series with PRESCIENT enables prediction of cell trajectories with interventions
Single-cell RNA-Seq allows us to observe snapshots of how biological systems change over time at cellular resolution. Here, the authors develop a generative framework that uses time-resolved single-cell data to model how cells change in physical time, including in response to perturbations.
- Grace Hui Ting Yeo
- , Sachit D. Saksena
- & David K. Gifford
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Article
| Open AccessGeneration of mature compact ventricular cardiomyocytes from human pluripotent stem cells
Cardiomyocytes of heart ventricles consist of subpopulations of trabecular and compact subtypes. Here the authors describe the generation of structurally, metabolically and functionally mature compact ventricular cardiomyocytes as well as mature atrial cardiomyocytes from human pluripotent stem cells.
- Shunsuke Funakoshi
- , Ian Fernandes
- & Gordon Keller
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| Open AccessClump sequencing exposes the spatial expression programs of intestinal secretory cells
Combining scRNA-seq with spatial information to enable the reconstruction of spatially-resolved cell atlases is challenging for rare cell types. Here the authors present ClumpSeq, an approach for sequencing small clumps of tissue attached cells, and apply it to establish spatial atlases for all secretory cell types in the small intestine.
- Rita Manco
- , Inna Averbukh
- & Shalev Itzkovitz
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Article
| Open AccessHox dosage contributes to flight appendage morphology in Drosophila
Here, the authors show that the Hox genes Antennapedia (Antp) and Ultrabithorax (Ubx) control flight appendage morphology in Drosophila. This role is dependent on a particular spatial expression profile and dosage, which was also found in evolutionary distant four-winged insect species.
- Rachel Paul
- , Guillaume Giraud
- & Samir Merabet
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Article
| Open AccessA stem cell population at the anorectal junction maintains homeostasis and participates in tissue regeneration
Transition zones connect distinct epithelia, contain cells expressing stem cell markers, and contribute to cancer development. Here, the authors examine the mouse anorectal junction, identifying a population of Krt17-positive basal cells that contribute to squamous and glandular epithelia during homeostasis and repair.
- Louciné Mitoyan
- , Véronique Chevrier
- & Géraldine Guasch
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Article
| Open AccessA coordinated progression of progenitor cell states initiates urinary tract development
Nephric duct (ND)-derived ureteric buds (UB) form the kidney collecting duct system, while ureteric tips promote nephron formation. Here the authors use single-cell RNA-seq and introduce Cluster RNA-seq to identify four progenitor populations in developing ND/UB regulated by the transcription factors Tfap2a/b and Gata3.
- Oraly Sanchez-Ferras
- , Alain Pacis
- & Maxime Bouchard
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Article
| Open AccessDifferential chromatin binding of the lung lineage transcription factor NKX2-1 resolves opposing murine alveolar cell fates in vivo
How transcription factors regulate cell fates in native tissues is unclear. Here, the authors report that differential chromatin binding of NKX2-1 determines opposing alveolar cell fates in the murine lung, showing loss of YAP/TAZ directs NKX2-1 to alternative binding sites leading to cell fate conversion.
- Danielle R. Little
- , Anne M. Lynch
- & Jichao Chen
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Article
| Open AccessSingle cell regulatory landscape of the mouse kidney highlights cellular differentiation programs and disease targets
Epigenetic and transcriptional dynamics are critical for both tissue homeostasis and injury response in the kidney. Leveraging a single cell multiomics atlas of the developing mouse kidney, the authors reveal key events in chromatin regulation and gene expression dynamics during postnatal development.
- Zhen Miao
- , Michael S. Balzer
- & Katalin Susztak
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Article
| Open AccessIntracellular trafficking of Notch orchestrates temporal dynamics of Notch activity in the fly brain
During Drosophila development, two peaks of Notch activity propagate across the neuroepithelium to generate neuroblasts. Here, the authors show Notch cis-inhibition under the control of intracellular Notch trafficking establishes these two peaks, which temporally control neurogenesis in the brain.
- Miaoxing Wang
- , Xujun Han
- & Makoto Sato
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Article
| Open AccessSpatiotemporal single-cell RNA sequencing of developing chicken hearts identifies interplay between cellular differentiation and morphogenesis
Using single-cell and spatial transcriptomics in chicken hearts, here, the authors generate a census of cellular interactions from early to late four-chambered heart stage, identifying a distinct epicardial-mesenchymal cell population with a migratory phenotype.
- Madhav Mantri
- , Gaetano J. Scuderi
- & Iwijn De Vlaminck
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Article
| Open AccessAsc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population
Adipose tissue is composed of a variety of cell types, including adipocyte precursor populations, that contribute to adipose tissue function upon differentiation. Here, using scRNA-sequencing of adolescent and adult mouse subcutaneous adipose tissue, the authors identify an Asc-1 positive preadipocyte population that is enriched in adolescent subcutaneous fat and demonstrate that loss of Asc-1 triggers spontaneous beige adipocyte differentiation.
- Lisa Suwandhi
- , Irem Altun
- & Siegfried Ussar
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Article
| Open AccessIdentifying transposable element expression dynamics and heterogeneity during development at the single-cell level with a processing pipeline scTE
How transposable elements (TE) contribute to cell fate changes is unclear. Here, the authors generate a pipeline to quantify TE expression from single cell data. They show the dynamic expression of TEs from gastrulation to somatic cell reprogramming and human disease
- Jiangping He
- , Isaac A. Babarinde
- & Jiekai Chen
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Article
| Open AccessEpidermal growth factor receptor signaling uncouples germ cells from the somatic follicular compartment at ovulation
Uncoupling of mature oocytes from somatic granulosa cells is required for their fertilization. Here the authors show that activation of EGFR signalling in granulosa cells during ovulation triggers ERK-dependent loss of filopodia oocyte adhesion, and Arp2/3 mediated retraction of granulosa cell filopodia.
- Laleh Abbassi
- , Stephany El-Hayek
- & Hugh J. Clarke
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Article
| Open AccessCre-Controlled CRISPR mutagenesis provides fast and easy conditional gene inactivation in zebrafish
Targeting a gene with two loxP sites is both time and labour intensive. Here the authors present Cre-Controlled CRISPR allowing conditional mutagenesis of a gene of interest and simultaneously labelling the putative mutant cells fluorescently.
- Stefan Hans
- , Daniela Zöller
- & Michael Brand