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| Open AccessA lineage-resolved cartography of microRNA promoter activity in C. elegans empowers multidimensional developmental analysis
By tracing promoter expression in lineage-mapped single cells, Xu et al. present a whole-body cartography of microRNA transcriptional activities during C. elegans embryogenesis and demonstrate its broad utility in multifaceted functional analyses.
- Weina Xu
- , Jinyi Liu
- & Zhuo Du
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Article
| Open AccessPIBF1 regulates trophoblast syncytialization and promotes cardiovascular development
The genetic link between placenta function and congenital heart defects has been established, though the cellular mechanisms underlying this connection is less clear. Here they show that PIBF1 regulates syncytiotrophoblast fusion and that loss of PIBF1 also negatively impacts heart development, providing a potential link between the development of these two organs.
- Jong Geol Lee
- , Jung-Min Yon
- & In-Jeoung Baek
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| Open AccessMARC-3, a membrane-associated ubiquitin ligase, is required for fast polyspermy block in Caenorhabditis elegans
In many sexually reproducing animals, the oocyte fuses with only one sperm during fertilization. Here, the authors show that C. elegans MARC-3, a membrane-associated RING-CH-type ubiquitin ligase, regulates polyspermy block after fertilization and maternal membrane protein degradation during the oocyte-to-embryo transition.
- Ichiro Kawasaki
- , Kenta Sugiura
- & Ken Sato
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| Open AccessSelf-renewing human naïve pluripotent stem cells dedifferentiate in 3D culture and form blastoids spontaneously
Blastoids are emerging models for early embryo development exploration in vitro. Here, authors found self-renewing human naïve PSCs spontaneously and efficiently give rise to blastoids upon three-dimensional suspension culture.
- Mingyue Guo
- , Jinyi Wu
- & José C. R. Silva
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| Open AccessReprogramming mechanism dissection and trophoblast replacement application in monkey somatic cell nuclear transfer
Somatic cloning of rhesus monkey has not been successful until now. Here, authors report epigenetic abnormalities in SCNT embryos and placentas and develop a trophoblast replacement method that enables them to successful clone of a healthy male rhesus monkey.
- Zhaodi Liao
- , Jixiang Zhang
- & Qiang Sun
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| Open AccessLeucine aminopeptidase1 controls egg deposition and hatchability in male Aedes aegypti mosquitoes
Aedes aegypti transmit several arboviruses and control of the mosquito populations could be beneficial. Here the authors show that deletion of leucine aminopeptidase1 (LAP1) results in mitochondrial defects and abnormal autophagy in sperm, reducing fertility and fecundity of females. LAP1−/− males show no obvious defects in longevity and mating fitness.
- Xiaomei Sun
- , Xueli Wang
- & Zhen Zou
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Article
| Open AccessIsoform-resolved transcriptome of the human preimplantation embryo
Human embryo development involves extensive transcriptional remodeling. In this study, the authors apply long- and short-read RNA-Seq to profile the transcriptomes of 73 human preimplantation embryos spanning zygotic to blastocyst stages, identifying tens of thousands of additional isoforms transcribed from both known and unannotated gene loci.
- Denis Torre
- , Nancy J. Francoeur
- & Robert Sebra
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| Open AccessMultimodal spatiotemporal transcriptomic resolution of embryonic palate osteogenesis
Multimodal spatiotemporal transcriptomic resolution of palatal osteogenesis identifies previously unreported enriched genes in developing palate, paving the way toward viable diagnostic and therapeutic targets for cleft palate disorders.
- Jeremie Oliver Piña
- , Resmi Raju
- & Rena N. D’Souza
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| Open AccessUnreprogrammed H3K9me3 prevents minor zygotic genome activation and lineage commitment in SCNT embryos
H3K9me3 is an epigenetic barrier to the reprogramming of somatic cells to a totipotent state during somatic cell nuclear transfer. Here, the authors uncover molecular mechanisms regulating H3K9me3 modifications in this process.
- Ruimin Xu
- , Qianshu Zhu
- & Xiaoyu Liu
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Article
| Open AccessspinDrop: a droplet microfluidic platform to maximise single-cell sequencing information content
Droplet microfluidics enables high-throughput single-cell sequencing, but often with increased noise. Here the authors report spinDrop (sorting picoinjection inDrop) to increase gene detection and reduce noise; they use this to generate a high-quality molecular atlas of mouse brain development.
- Joachim De Jonghe
- , Tomasz S. Kaminski
- & Florian Hollfelder
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| Open AccessMaternal TDP-43 interacts with RNA Pol II and regulates zygotic genome activation
Zygotic genome activation is crucial for mammalian embryonic development. Here, the authors find that TDP-43 is indispensable for mouse embryonic development and mediates zygotic genome activation through Pol II configuration.
- Xiaoqing Nie
- , Qianhua Xu
- & Lei Li
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Article
| Open AccessSingle cell Hi-C identifies plastic chromosome conformations underlying the gastrulation enhancer landscape
Here the authors use single-cell Hi-C to investigate chromosome conformation in post-gastrulation mouse embryos. They find a distinct genome organization in primitive erythrocytes and conformations matching the mesodermal and ectodermal lineages.
- Nimrod Rappoport
- , Elad Chomsky
- & Amos Tanay
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Article
| Open AccessCFP1 governs uterine epigenetic landscapes to intervene in progesterone responses for uterine physiology and suppression of endometriosis
Progesterone (P4) signalling is involved in physiological control of the endometrium and contributes to the pathogenesis of endometrial diseases such as endometriosis. Here the authors report that CFP1, a regulator of histone methylation, controls endometrial responses to P4 and lack of endometrial CFP1 leads to failure of embryo implantation and exacerbated experimental endometriosis in mice.
- Seung Chel Yang
- , Mira Park
- & Haengseok Song
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Article
| Open AccessCopy number variation in tRNA isodecoder genes impairs mammalian development and balanced translation
Enigmatically tRNA genes exist in several hundred copies in mammalian genomes. Here the authors find a precipitous failure of development and increased amino acid misincorporation upon systematic elimination of tRNA-Phe genes in mice using CRISPR.
- Laetitia A. Hughes
- , Danielle L. Rudler
- & Aleksandra Filipovska
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| Open AccessLSM1-mediated Major Satellite RNA decay is required for nonequilibrium histone H3.3 incorporation into parental pronuclei
Asymmetric histone modifications in parental pronuclei displays epigenetic regulation. Here the authors reveal the role of LSM1-mediated Major Satellite RNA decay in the H3 variant incorporation and modifications in male pronucleus.
- Jiang Zhu
- , Kang Chen
- & Lan Kang
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Article
| Open AccessCreb5 coordinates synovial joint formation with the genesis of articular cartilage
Zhang et al. show that the Creb5 transcription factor regulates the formation of synovial joints, directs the genesis of articular cartilage, and regulates the shape of the ends of long bones by blocking Wnt5a expression in the perichondrium.
- Cheng-Hai Zhang
- , Yao Gao
- & Andrew B. Lassar
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Article
| Open AccessThe first mitotic division of human embryos is highly error prone
Human beings arise from serial mitotic divisions of a single fertilised egg. Here through live cell imaging of fertilized embryos the authors show that the first mitotic division is error prone and can contribute to preimplantation mosaicism.
- Cerys E. Currie
- , Emma Ford
- & Andrew D. McAinsh
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Article
| Open AccessMembrane potential drives the exit from pluripotency and cell fate commitment via calcium and mTOR
The plasma membrane’s electrical potential is maintained by ion channels, though the impact of this potential on cell fate has not been clearly elucidated. Here they show that changes in membrane potential can affect calcium levels and mTOR in pluripotent stem cells, altering their transition from pluripotency to differentiation.
- Emily Sempou
- , Valentyna Kostiuk
- & Mustafa K. Khokha
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| Open AccessDifferential 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
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| Open AccessSomatic cell fate maintenance in mouse fetal testes via autocrine/paracrine action of AMH and activin B
Fate determination and maintenance of foetal testes in most animals occurs cell autonomously. Here the authors show in mouse XY embryos that Sertoli cell derived AMH and activin B together maintain Sertoli cell identity, and lack of both AMH and activin B leads to transdifferentiation into female granulosa cells.
- Karina F. Rodriguez
- , Paula R. Brown
- & Humphrey Hung-Chang Yao
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| Open AccessNuclear speed and cycle length co-vary with local density during syncytial blastoderm formation in a cricket
Early in insect embryo development, many nuclei share one large cell, travel varied paths and self-organize into a single layer. Donoughe et al. illuminate this process with live-imaging, modeling, and experimental changes to the embryo’s shape.
- Seth Donoughe
- , Jordan Hoffmann
- & Cassandra G. Extavour
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Article
| Open AccessHealthy cloned offspring derived from freeze-dried somatic cells
The development of safe preservation methods for genetic resources is important. Here, the authors successfully produce cloned mice from freeze-dried somatic cells, demonstrating the possibility of safe and low-cost preservation of genetic resources.
- Sayaka Wakayama
- , Daiyu Ito
- & Teruhiko Wakayama
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Article
| Open AccessDDX1 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
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Article
| Open AccessLimiting motorboat noise on coral reefs boosts fish reproductive success
Using a season-long field manipulation with an established model fish system on the Great Barrier Reef, this study demonstrates that limiting motorboat activity on reefs leads to faster growth and survival of more fish offspring compared to reefs experiencing busy motorboat traffic. Noise mitigation and abatement could therefore present a valuable opportunity for enhancing ecosystem resilience.
- Sophie L. Nedelec
- , Andrew N. Radford
- & Stephen D. Simpson
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| Open AccessGlobal ubiquitinome profiling identifies NEDD4 as a regulator of Profilin 1 and actin remodelling in neural crest cells
Here the authors combine multi-omics approaches to uncover a role for ubiquitination and the ubiquitin ligase NEDD4 in targeting the actin binding protein Profilin 1 to regulate actin polymerisation in neural crest cells.
- Iman Lohraseb
- , Peter McCarthy
- & Quenten Schwarz
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| Open AccessThe control of transcriptional memory by stable mitotic bookmarking
Using quantitative imaging and monitoring transcription in living embryos, Bellec et al., provide evidence that the pioneer factor GAF acts as a stable mitotic bookmarker during early Drosophila development.
- Maëlle Bellec
- , Jérémy Dufourt
- & Mounia Lagha
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Article
| Open AccessSingle-cell analysis identifies a key role for Hhip in murine coronal suture development
Craniofacial development depends on formation and maintenance of sutures between bones of the skull. Here the authors identify enriched expression of the hedgehog inhibitor Hhip, specifically in the mesenchyme of the murine coronal suture, and show sutural dysgenesis in Hhip−/− mutants.
- Greg Holmes
- , Ana S. Gonzalez-Reiche
- & Ethylin Wang Jabs
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Article
| Open AccessConserved and species-specific chromatin remodeling and regulatory dynamics during mouse and chicken limb bud development
The vertebrate limb bud is a paradigm to uncover the fundamental mechanisms that govern embryogenesis and evolutionary diversification. Here the authors compare mouse and chicken limb bud development to study the impact of genome evolution on conserved and divergent gene regulatory interactions.
- Shalu Jhanwar
- , Jonas Malkmus
- & Rolf Zeller
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Article
| Open AccessBioengineered embryoids mimic post-implantation development in vitro
Previous approaches to derive embryoids either lack physiological morphology and signaling interactions, or are unconducive to model post-gastrulation development. Here the authors use a high-throughput approach to induce mouse embryonic stem cells into epiblast-like aggregates, which are then co-cultured with mouse trophoblast stem cell aggregates, to yield embryoids with axial morphogenesis and anterior development.
- Mehmet U. Girgin
- , Nicolas Broguiere
- & Matthias P. Lutolf
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| Open AccessAmnion signals are essential for mesoderm formation in primates
Human and murine embryonic development has disparities, highlighting the need for primate systems. Here, the authors construct a post-implantation transcriptional atlas from non-human primate embryos and show ISL1 controls a gene regulatory network in the amnion required for mesoderm formation.
- Ran Yang
- , Alexander Goedel
- & Kenneth R. Chien
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Article
| Open AccessFluid flow-induced left-right asymmetric decay of Dand5 mRNA in the mouse embryo requires a Bicc1-Ccr4 RNA degradation complex
Questioning what regulates left-right asymmetry breaking in the mouse node: the authors identify a 200 bp stretch of the Dand5 3’UTR where Bicc1 binds, and Cnot proteins downstream of calcium flow regulate the post-transcriptional regulation of Dand5 by Bicc1.
- Katsura Minegishi
- , Benjamin Rothé
- & Hiroshi Hamada
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| Open AccessSingle-cell multiomics sequencing reveals the functional regulatory landscape of early embryos
Extensive epigenetic reprogramming occurs during preimplantation embryo development. Here the authors develop a single cell multiomics sequencing technology that enables profiling of genome-wide chromatin accessibility, DNA methylation and RNA expression in the same individual cell and apply this method to study mouse preimplantation embryos.
- Yang Wang
- , Peng Yuan
- & Liying Yan
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| Open AccessWnt/Beta-catenin/Esrrb signalling controls the tissue-scale reorganization and maintenance of the pluripotent lineage during murine embryonic diapause
Embryonic diapause is a state of dormancy with poorly understood mechanisms of embryo intrinsic regulation. Here, the authors show that murine diapause is a dynamic process, where tissue-scale reorganization of the pluripotent lineage is controlled in an autocrine manner by the Wnt/b-catenin/Esrrb signalling cascade.
- Rui Fan
- , Yung Su Kim
- & Ivan Bedzhov
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| Open AccessE-cadherin focuses protrusion formation at the front of migrating cells by impeding actin flow
The arrival of migratory cells at their targets relies on following precise routes within tissues. Here the authors demonstrate that the cell adhesion molecule E-cadherin can control the path of cell migration by confining the site where bleb-type protrusions form within the cell front.
- Cecilia Grimaldi
- , Isabel Schumacher
- & Erez Raz
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| Open AccessPrecise allele-specific genome editing by spatiotemporal control of CRISPR-Cas9 via pronuclear transplantation
Injecting Cas9 and gRNA into an animal zygote often produces mosaicism and random biallelic targeting. Here, the authors use pronuclear transfer to reduce mosaicism and selectively target parental alleles.
- Yanhe Li
- , Yuteng Weng
- & Shaorong Gao
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| Open AccessTransgenerational inheritance of impaired larval T cell development in zebrafish
Evidence for transgenerational inheritance of epigenetic information in vertebrates is scarce. Here the authors report that homozygous dnmt1 mutant zebrafish are essentially normal, with the exception of impaired lymphopoiesis, with impaired larval (but not adult) T cell development being transmitted to subsequent generations by genotypically wildtype fish.
- Norimasa Iwanami
- , Divine-Fondzenyuy Lawir
- & Thomas Boehm
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| Open AccessGenes with spiralian-specific protein motifs are expressed in spiralian ciliary bands
Spiralians have ciliary bands, used for locomotion and feeding, but defining molecular features of these structures are unknown. Here, the authors report a gene, Lophotrochin, that contains a protein domain only found in spiralians, and specifically expressed in diverse ciliary bands across the group, which provides a molecular signature for these structures.
- Longjun Wu
- , Laurel S. Hiebert
- & J. David Lambert
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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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| 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 AccessSupernumerary B chromosomes of Aegilops speltoides undergo precise elimination in roots early in embryo development
B chromosomes are supernumerary chromosomes exhibiting dramatic differences between different organs in same species. Here, the authors show programmed B chromosome elimination in goatgrass starts at the onset of embryo differentiation by nondisjunction of chromatids, anaphase lagging, and ends with the degradation of micronucleated DNA.
- Alevtina Ruban
- , Thomas Schmutzer
- & Andreas Houben
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Article
| Open AccessChromatin architecture reorganization in murine somatic cell nuclear transfer embryos
The organisation of chromatin in somatic cell nuclear transfer (SCNT) embryos remains poorly understood. Here, the authors examine higher order chromatin structures of mouse SCNT embryos and provide insights into chromatin architecture reorganisation during SCNT embryo development.
- Mo Chen
- , Qianshu Zhu
- & Shaorong Gao
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Article
| Open AccessThe RNA-binding protein DAZL functions as repressor and activator of mRNA translation during oocyte maturation
The RNA binding protein DAZL plays a critical role during germ cell development. Here the authors provide evidence that DAZL functions both as activator and repressor of translation during oocyte maturation in mouse.
- Cai-Rong Yang
- , Gabriel Rajkovic
- & Marco Conti
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Article
| Open AccessIGF1-mediated human embryonic stem cell self-renewal recapitulates the embryonic niche
The signals regulating the establishment and maintenance of the pluripotent epiblast in human embryos are unclear. Here, the authors use a bioinformatics approach to identify the role of IGF1 in human embryo development, and from this, propose a culture medium with IGF1 together with Activin to sustain hESCs in the absence of FGF.
- Sissy E. Wamaitha
- , Katarzyna J. Grybel
- & Kathy K. Niakan
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Article
| Open AccessTissue mechanics drives regeneration of a mucociliated epidermis on the surface of Xenopus embryonic aggregates
The role of tissue mechanics in the regeneration of mucociliated epithelium in Xenopus is unclear. Here, the authors show that Xenopus ectoderm aggregates undergo epithelial-like phenotypic transition prior to differentiation of mucus-secreting goblet cells to enable regeneration.
- Hye Young Kim
- , Timothy R. Jackson
- & Lance A. Davidson
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Article
| Open AccessTet inactivation disrupts YY1 binding and long-range chromatin interactions during embryonic heart development
Tet-mediated DNA demethylation is intimately involved in reguatling embryonic development. Here the authors characterise DNA methylation and hydroxymethylation dynamics during early cardiac development in both human and mice and provide evidence that Tet-mediated DNA demethylation plays a role in regulating chromatin organization during early heart development.
- Shaohai Fang
- , Jia Li
- & Yun Huang
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Article
| Open AccessPre- and peri-implantation Zika virus infection impairs fetal development by targeting trophectoderm cells
Here, using human cells and mouse models, the authors show that Zika virus can infect preimplantation trophectoderm. Pre-implantation infection can affect nervous system development and survival of neural progenitors, and can result in miscarriage or spontaneous abortion.
- Lei Tan
- , Lauretta A. Lacko
- & Shuibing Chen
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Article
| Open AccessA conserved regulatory program initiates lateral plate mesoderm emergence across chordates
Numerous tissues are derived from the lateral plate mesoderm (LPM) but how this is specified is unclear. Here, the authors identify a pan-LPM reporter activity found in the zebrafish draculin (drl) gene that also shows transgenic activity in LPM-corresponding territories of several chordates, including chicken, axolotl, lamprey, Ciona, and amphioxus.
- Karin D. Prummel
- , Christopher Hess
- & Christian Mosimann
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| Open AccessSingle-cell CAS-seq reveals a class of short PIWI-interacting RNAs in human oocytes
PIWI-interacting RNAs (piRNAs) are ~25–33 nt small RNAs expressed in animal germ cells. Here, the authors develop a single-cell small RNA sequencing method and report that a class of ~20-nt piRNAs lacking 3′ end 2′-O-methylation are associated with PIWIL3 protein and predominantly expressed in human and monkey oocytes.
- Qiyuan Yang
- , Ronghong Li
- & Ligang Wu
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Article
| Open AccessA Hox-TALE regulatory circuit for neural crest patterning is conserved across vertebrates
Mechanisms coupling Hox genes to neural crest are largely unknown. Here, the authors use cross species regulatory comparisons between the Hox2 genes of jawed vertebrates and lamprey, a jawless vertebrate, finding a conserved ancestral mechanism for Hox2 neural crest regulation.
- Hugo J. Parker
- , Bony De Kumar
- & Robb Krumlauf