Featured
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Article
| Open AccessPluripotency factors determine gene expression repertoire at zygotic genome activation
Zygotic genome activation in zebrafish relies on pluripotency transcription factors Pou5f3 and Sox19b. Here the authors investigate how these factors interact in vivo by analyzing the changes in chromatin state and time-resolved transcription in Pou5f3 and Sox19b single and double mutant embryos.
- Meijiang Gao
- , Marina Veil
- & Daria Onichtchouk
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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 AccessLima1 mediates the pluripotency control of membrane dynamics and cellular metabolism
How pluripotency transcription factors regulate the cellular architecture and energetics has remained largely unknown. Here the authors identify Lima1 as a key effector that mediates the pluripotency control of membrane dynamics and cellular metabolism.
- Binyamin Duethorn
- , Fabian Groll
- & Ivan Bedzhov
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Article
| Open AccessNodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids
Studying morphogen gradient formation and reception in mammalian development is challenging. Here, the authors show with human gastruloids that Nodal activity in live cells spreads via a relay mechanism with timing that is locally controlled by Lefty, which dictates mesoderm differentiation timing.
- Lizhong Liu
- , Anastasiia Nemashkalo
- & Aryeh Warmflash
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Article
| Open AccessInduction of Rosette-to-Lumen stage embryoids using reprogramming paradigms in ESCs
Synthetic embryo models have arisen as an approach to probe early development in vitro, facilitating the study of difficult to access stages. Here the authors present a simple system for generating embryo-like structures that resemble peri-implantation mouse embryos.
- Jan Langkabel
- , Arik Horne
- & Hubert Schorle
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Article
| Open AccessType-I collagen produced by distinct fibroblast lineages reveals specific function during embryogenesis and Osteogenesis Imperfecta
Collagen is the most abundant protein in the human body. Here, the authors show that different classes of fibroblasts produce collagen of unique functions with different impacts on embryo development and bone formation.
- Yang Chen
- , Sujuan Yang
- & Raghu Kalluri
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Article
| Open AccessRepression of germline genes by PRC1.6 and SETDB1 in the early embryo precedes DNA methylation-mediated silencing
Germline genes are repressed by DNA methylation and histone marks. Here, the authors show that specific germline genes hypomethylated pre-implantation are enriched for PRC1.6, H2AK119ub1 and H3K9me3, which coordinately repress their expression.
- Kentaro Mochizuki
- , Jafar Sharif
- & Matthew C. Lorincz
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Article
| Open AccessSingle cell multi-omic analysis identifies a Tbx1-dependent multilineage primed population in murine cardiopharyngeal mesoderm
Perturbations of the cardiopharyngeal mesoderm can lead to congenital defects in individuals with 22q11.2 deletion syndrome. Here the authors use single cell RNA-sequencing to identify a multilineage primed population within the mesoderm, marked by Tbx1, which has bipotent properties to form cardiac and branchiomeric muscle cells.
- Hiroko Nomaru
- , Yang Liu
- & Bernice E. Morrow
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Article
| Open AccessSmad4 controls signaling robustness and morphogenesis by differentially contributing to the Nodal and BMP pathways
The role of the transcriptional effector SMAD4 in vertebrate embryo development remains unresolved. Here the authors show that in the absence of Smad4, dorsal/ventral embryo patterning is disrupted due to the loss of BMP signaling, while Nodal signaling is maintained, but insufficient for optimal endoderm specification.
- Luca Guglielmi
- , Claire Heliot
- & Caroline S. Hill
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Article
| Open AccessSatb2 acts as a gatekeeper for major developmental transitions during early vertebrate embryogenesis
Activation of the zygotic genome is a critical transition during development, though the link to tissue-specific gene regulation remains unclear. Here the authors demonstrate distinct functions for Satb2 before and after zygotic genome activation, highlighting the temporal coordination of these roles.
- Saurabh J. Pradhan
- , Puli Chandramouli Reddy
- & Sanjeev Galande
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Article
| Open AccessIdentical twins carry a persistent epigenetic signature of early genome programming
The mechanisms underlying how monozygotic (or identical) twins arise are yet to be determined. Here, the authors investigate this in an epigenome-wide association study, showing that monozygotic twinning has a characteristic DNA methylation signature in adult somatic tissues.
- Jenny van Dongen
- , Scott D. Gordon
- & Dorret I. Boomsma
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Article
| Open AccessReconstructing aspects of human embryogenesis with pluripotent stem cells
Human early development remains largely inaccessible, owing to technical and ethical limitations of working with natural embryos. Here the authors assess the extent to which human expanded pluripotent stem cells can specify distinct cell lineages and capture aspects of early human embryogenesis.
- Berna Sozen
- , Victoria Jorgensen
- & Magdalena Zernicka-Goetz
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Article
| Open AccessBicc1 and Dicer regulate left-right patterning through post-transcriptional control of the Nodal inhibitor Dand5
The authors show that post-transcriptional regulation of the cilia-driven leftward flow target dand5 is central to symmetry breakage in frog, fish and mouse and is mediated by a 139 nt Bicc1 responsive element in the dand5 3′UTR, and they present evidence that Pkd2 regulates this Bicc1/dand5 module.
- Markus Maerker
- , Maike Getwan
- & Axel Schweickert
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Article
| Open AccessA TALE/HOX code unlocks WNT signalling response towards paraxial mesoderm
Cells in the developing embryo interpret WNT signalling with context-dependence, but the mechanism decoding these cues is unclear. Here, the authors show that combinatorial TALE/HOX activity destabilizes nucleosomes at WNT-responsive regions to activate paraxial mesodermal genes.
- Luca Mariani
- , Xiaogang Guo
- & Elisabetta Ferretti
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Comment
| Open AccessThe evolution of our understanding of human development over the last 10 years
As it fulfills an irresistible need to understand our own origins, research on human development occupies a unique niche in scientific and medical research. In this Comment, we explore the progress in our understanding of human development over the past 10 years. The focus is on basic research, clinical applications, and ethical considerations.
- Ali H. Brivanlou
- & Norbert Gleicher
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Comment
| Open AccessHow will our understanding of human development evolve over the next 10 years
In the next 10 years, the continued exploration of human embryology holds promise to revolutionize regenerative and reproductive medicine with important societal consequences. In this Comment we speculate on the evolution of recent advances made and describe emerging technologies for basic research, their potential clinical applications, and, importantly, the ethical frameworks in which they must be considered.
- Ali H. Brivanlou
- , Nicolas Rivron
- & Norbert Gleicher
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Article
| Open AccessCoordination of endothelial cell positioning and fate specification by the epicardium
It remains unclear how spatial information controls endothelial cell identity and behavior in the developing heart. Here the authors perform single cell RNA sequencing at key developmental timepoints in mice to interrogate cellular contributions to coronary vessel patterning and maturation in the epicardium.
- Pearl Quijada
- , Michael A. Trembley
- & Eric M. Small
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Article
| Open AccessA dynamic basal complex modulates mammalian sperm movement
Centrioles are ancient organelles with a conserved architecture and their rigidity is thought to restrict microtubule sliding. Here authors show that, in mammalian sperm, the atypical distal centriole and its surrounding atypical pericentriolar matrix form a dynamic basal complex that facilitates a cascade of internal sliding deformations, coupling tail beating with asymmetric head kinking.
- Sushil Khanal
- , Miguel Ricardo Leung
- & Tomer Avidor-Reiss
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Article
| Open AccessA single cell characterisation of human embryogenesis identifies pluripotency transitions and putative anterior hypoblast centre
Single cell analysis of early human embryos identifies key changes in pluripotency, the requirement of FGF signalling for embryo survival, and defines a putative anterior-like region of hypoblast cells, providing insights into how early human development is regulated.
- Matteo A. Molè
- , Tim H. H. Coorens
- & Magdalena Zernicka-Goetz
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Article
| Open AccessMaternal iron deficiency perturbs embryonic cardiovascular development in mice
From mouse experiments, the authors link iron deficiency in mothers with cardiovascular defects and increased retinoic acid signalling in their offspring, and giving iron early in pregnancy can prevent most defects.
- Jacinta I. Kalisch-Smith
- , Nikita Ved
- & Duncan B. Sparrow
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Article
| Open AccessVangl2 promotes the formation of long cytonemes to enable distant Wnt/β-catenin signaling
Cytonemes are cellular projections known to transfer Wnt ligands between cells, but their regulation remains unclear. Here, the authors show that activation of the planar cell polarity protein Vangl2 generates long and branched cytonemes increasing paracrine Wnt/β-catenin signaling.
- Lucy Brunt
- , Gediminas Greicius
- & Steffen Scholpp
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Article
| Open AccessThe deubiquitinase Usp9x regulates PRC2-mediated chromatin reprogramming during mouse development
During development, H3K27me3 is reallocated from large domains in preimplantation embryos to mark promoters of developmental genes. Here the authors show that the deubiquitinase Usp9x interacts with, deubiquitinates and stabilizes PRC2 and provide evidence that a Usp9x-PRC2 regulatory axis is critical at peri-implantation.
- Trisha A. Macrae
- & Miguel Ramalho-Santos
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Article
| Open AccessGermline inherited small RNAs facilitate the clearance of untranslated maternal mRNAs in C. elegans embryos
In animal embryos, maternally deposited mRNAs are degraded by several different mechanisms. Here the authors show that C. elegans embryos inherit antisense pool of small RNAs which are loaded into CSR-1 and cleave complementary maternal mRNAs.
- Piergiuseppe Quarato
- , Meetali Singh
- & Germano Cecere
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Article
| Open AccessStrand-specific single-cell methylomics reveals distinct modes of DNA demethylation dynamics during early mammalian development
Erasure of DNA methylation from the parental genomes is critical to reset the methylome of differentiated gametes to pluripotent cells in the blastocyst. Here, the authors present a high-throughput single-cell method that enables strand-specific quantification of DNA methylation and identify distinct modes of DNA demethylation dynamics during early mammalian development.
- Maya Sen
- , Dylan Mooijman
- & Alexander van Oudenaarden
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Article
| Open AccessTwo mechanisms drive pronuclear migration in mouse zygotes
In a newly fertilized egg, maternal and paternal chromosomes are enclosed in two separate pronuclei but the mechanisms in mammals for pronuclear movement are unclear. Here, the authors report that both F-actin and microtubule polymerization act in concern to drive inward movement of pronuclei towards the cell centre.
- Kathleen Scheffler
- , Julia Uraji
- & Melina Schuh
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Article
| Open AccessEstablishment of a morphological atlas of the Caenorhabditis elegans embryo using deep-learning-based 4D segmentation
The systematic characterization of C. elegans morphology during development has yet to be performed. Here, the authors produce a 3D atlas of C. elegans morphology from 17 embryos and 54 developmental stages, using an automated pipeline, CShaper (combining segmentation of fluorescently labeled membranes with automated cell lineage tracing).
- Jianfeng Cao
- , Guoye Guan
- & Hong Yan
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Article
| Open AccessMaternal DNMT3A-dependent de novo methylation of the paternal genome inhibits gene expression in the early embryo
The paternal genome in mice undergoes widespread DNA methylation loss post-fertilization. Here, the authors apply allele-specific analysis of WGBS data to show that a number of genomic regions are simultaneously de novo methylated on the paternal genome dependent on maternal DNMT3A activity, which induces transcriptional silencing of this allele in the early embryo.
- Julien Richard Albert
- , Wan Kin Au Yeung
- & Matthew Lorincz
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Article
| Open AccessSingle-cell transcriptomics identifies divergent developmental lineage trajectories during human pituitary development
Editor’s summary_NCOMMS-19-41732B The anterior pituitary gland controls body growth and reproduction but how early development is dynamically regulated is unclear. Here, the authors use scRNA-seq of human fetal pituitaries to identify different developmental routes and state transitions of five hormone-producing cell lineages, and a hybrid epithelial/mesenchymal state of pituitary stem cells.
- Shu Zhang
- , Yueli Cui
- & Jie Qiao
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Article
| Open AccessDynamics and clinical relevance of maternal mRNA clearance during the oocyte-to-embryo transition in humans
How maternal RNA clearance is regulated in human preimplantation embryos is unclear. Here, the authors show there is a potential correlation between maternal mRNA decay defects and early developmental arrest from in vitro fertilized human embryos, suggesting that M-decay and Z-decay pathways may regulate such early development.
- Qian-Qian Sha
- , Wei Zheng
- & Heng-Yu Fan
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Article
| Open AccessChromatin remodeling in bovine embryos indicates species-specific regulation of genome activation
Preimplantation embryos undergo extensive transcriptomic and epigenomic remodeling. Here the authors assay open chromatin in bovine oocytes, embryos, and embryonic stem cells, and compare the transcriptomes and epigenomes of cattle, human and mouse embryos, revealing species-specific regulation of genome activation.
- Michelle M. Halstead
- , Xin Ma
- & Pablo J. Ross
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Article
| Open AccessATAC-seq footprinting unravels kinetics of transcription factor binding during zygotic genome activation
Footprinting analysis allows genome-wide investigation of transcription factor (TF) binding on chromatin. Here the authors developed a framework termed TOBIAS aimed at identifying footprints of chromatin-associated proteins from ATAC-seq accessibility profiles and apply it to zygotic development datasets.
- Mette Bentsen
- , Philipp Goymann
- & Mario Looso
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Article
| Open AccessYbx1 fine-tunes PRC2 activities to control embryonic brain development
Polycomb repressive complex 2 (PRC2) methylates H3K27 and suppresses RNA polymerase II transcription by promoting a closed chromatin. Here the authors identify the transcription factor Ybx1 as an interactor that regulates the binding of PRC2 to chromatin and H3K27 methylation to promote the genetic programs underlying neural lineages and neural progenitor self-renewal–differentiation choices.
- Myron K. Evans
- , Yurika Matsui
- & Jamy C. Peng
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Article
| Open AccessDevelopmental potential of aneuploid human embryos cultured beyond implantation
Aneuploidy, abnormal chromosome number, is a major cause of early pregnancy loss. Here the authors determine the extent of post-implantation development of human embryos with common aneuploidies in culture, finding developmental arrest of monosomy 21 embryos, and trophoblast hypo-proliferation in trisomy 16 embryos.
- Marta N. Shahbazi
- , Tianren Wang
- & Magdalena Zernicka-Goetz
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Article
| Open AccessEpigenetic homogeneity in histone methylation underlies sperm programming for embryonic transcription
In addition to paternal genetic material, sperm contributes epigenetic information to the embryo to efficiently support development. Here, the authors demonstrate a homogeneous paternal contribution to epigenetic information via sperm-derived modified histone transmission to the developing vertebrate embryo.
- Mami Oikawa
- , Angela Simeone
- & Jerome Jullien
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Article
| Open AccessThe MiDAC histone deacetylase complex is essential for embryonic development and has a unique multivalent structure
The MiDAC complex recruits class I histone deacetylases to chromatin but little is known about its precise structure and function. Here, the authors explore the role of MiDAC in the cell cycle and during mouse embryogenesis, and present cryoEM structures that provide insight into MiDAC’s mode of assembly.
- Robert E. Turnbull
- , Louise Fairall
- & John W. R. Schwabe
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Article
| Open AccessAutophagy-mediated apoptosis eliminates aneuploid cells in a mouse model of chromosome mosaicism
The mechanisms behind the plasticity of embryos and how they deal with aneuploid cells are unclear. Here, the authors show that aneuploid cells in a mouse embryo are preferentially eliminated during pre- and peri-implantation development in a p53-dependent process involving both autophagy and apoptosis.
- Shruti Singla
- , Lisa K. Iwamoto-Stohl
- & Magdalena Zernicka-Goetz
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Article
| Open AccessThe BCL-2 pathway preserves mammalian genome integrity by eliminating recombination-defective oocytes
If left unrepaired, meiotic DSBs are toxic to mammalian cells, thus oocytes in which DSBs persist are eliminated by the DNA-damage checkpoint. Here the authors provide insights into the roles of PUMA, NOXA and BAX during DNA damage checkpoint that eliminates Dmc1−/− and Msh5−/− oocytes.
- Elias ElInati
- , Agata P. Zielinska
- & James M. A. Turner
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Article
| Open AccessMulti-level and lineage-specific interactomes of the Hox transcription factor Ubx contribute to its functional specificity
Many transcription factors regulate gene expression in a lineage- and process-specific manner, despite being expressed in several cell types. Here, the authors show that the Hox transcription factor Ubx has lineage-specific interactomes, which contribute to its cell context-dependent functions.
- Julie Carnesecchi
- , Gianluca Sigismondo
- & Ingrid Lohmann
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Article
| Open AccessBEN-solo factors partition active chromatin to ensure proper gene activation in Drosophila
The BEN-solo proteins—including Insensitive (Insv), Elba1 and Elba2—function in both transcriptional repression and chromatin insulation. Here, the authors investigate the role of these proteins in Drosophila embryos, finding that ELBA and Insv function as general insulators and partition active chromatin to ensure proper gene activation in Drosophila.
- Malin Ueberschär
- , Huazhen Wang
- & Qi Dai
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Article
| Open AccessMouse embryo geometry drives formation of robust signaling gradients through receptor localization
How receptor localization affects morphogen gradient formation during embryonic development is unclear. Here, the authors study the relationship between the BMP gradient, receptor localization, and compartmentalized geometry in the early mouse embryo, using experimental data and computational simulation.
- Zhechun Zhang
- , Steven Zwick
- & Sharad Ramanathan
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Article
| Open AccessCatalytically inactive Dnmt3b rescues mouse embryonic development by accessory and repressive functions
The family of DNA methyltransferases (Dnmts) consists of four catalytically active enzymes that catalyze DNA methylation and also play a role as transcriptional regulators. Here the authors show that catalytically inactive Dnmt3b rescues a majority of methylation and expression changes in the absence of Dnmt3b during mouse embryonic development.
- Pawel Nowialis
- , Katarina Lopusna
- & Rene Opavsky
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Article
| Open AccessIn vivo Hox binding specificity revealed by systematic changes to a single cis regulatory module
Hox proteins are expressed in partially overlapping regions to inform development along the embryo’s head-tail axis. Here the authors analyse a cis regulatory module directly regulated by seven different Drosophila Hox proteins to uncover how different Hox class proteins differentially control its expression.
- Carlos Sánchez-Higueras
- , Chaitanya Rastogi
- & James C.-G. Hombría
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Article
| Open AccessBlood stem cell-forming haemogenic endothelium in zebrafish derives from arterial endothelium
HSCs emerge from haemogenic endothelium (HE) in the dorsal aorta but whether these tissues share a common lineage is unclear. Here, the authors use a zebrafish runx1 reporter to show that HE maintains an arterial gene expression profile in the absence of Runx1, suggesting the aortic endothelium as a precursor of HE.
- Florian Bonkhofer
- , Rossella Rispoli
- & Roger Patient
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Article
| Open AccessMorphogenesis of extra-embryonic tissues directs the remodelling of the mouse embryo at implantation
How the shape of the pre-implantation murine embryo changes dramatically upon implantation is unclear. Here, the authors use live imaging with a cdx2-GFP reporter line in combination with loss of function experiments to demonstrate that FGF signalling mediated trophectoderm morphogenesis orchestrates this process.
- Neophytos Christodoulou
- , Antonia Weberling
- & Magdalena Zernicka-Goetz
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Article
| Open AccessSpinal neural tube closure depends on regulation of surface ectoderm identity and biomechanics by Grhl2
Loss or over-expression of Grainyhead-like transcription factors (Grhl) prevents closure of the neural tube but the mechanism underlying this is unclear. Here, the authors show that Grhl2 regulates murine posterior-neuropore closure via changes in the identity and biomechanics of the non-neural, surface ectoderm cells.
- Evanthia Nikolopoulou
- , Caroline S. Hirst
- & Nicholas D. E. Greene
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Article
| Open AccessPrimary cilia regulate hematopoietic stem and progenitor cell specification through Notch signaling in zebrafish
Haematopoietic stem and progenitor cells (HSPCs) produce all blood lineages and arise from the haemogenic endothelium (HE) during embryogenesis. Here the authors show that genes specific to cilia formation are required for HSPC development in the HE in zebrafish through transduction of Notch signal.
- Zhibin Liu
- , Haiqing Tu
- & Feng Liu
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Article
| Open AccessThe maternal to zygotic transition regulates genome-wide heterochromatin establishment in the zebrafish embryo
Eukaryotic genomes are segregated into euchromatin and heterochromatin. Here the authors show that heterochromatin establishment during zebrafish embryo development is controlled by zygotic transcription of miR-430 and subsequent degradation of maternal transcripts encoding the chromatin remodeling protein Smarca2.
- Kathrin Laue
- , Srivarsha Rajshekar
- & Mary G. Goll
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Article
| Open AccessImplantation initiation of self-assembled embryo-like structures generated using three types of mouse blastocyst-derived stem cells
The precise cellular patterning and decisions of early embryogenesis have been hard to mimic in vitro. Here, the authors culture murine embryonic and trophoblast stem cells together with extra-embryonic endoderm stem cells to form embryo-like structures (ETX-embryoids), which can initiate an implantation response.
- Shaopeng Zhang
- , Tianzhi Chen
- & Jianyong Han
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Article
| Open AccessAn integrated chromatin accessibility and transcriptome landscape of human pre-implantation embryos
Early human embryonic development involves extensive changes in chromatin structure and transcriptional activity. Here the authors present LiCAT-seq, a method enabling simultaneous profiling of chromatin accessibility and gene expression with ultra-low input of cells and map chromatin accessibility and transcriptome landscapes for human pre-implantation embryos.
- Longqi Liu
- , Lizhi Leng
- & Ge Lin