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Perspective
| Open AccessThe long and winding road of reprogramming-induced rejuvenation
Rejuvenation and partial reprogramming are two frontier areas in the field of aging. Here, the authors summarize advances in these fields and suggest future directions for research and therapy.
- Ali Doğa Yücel
- & Vadim N. Gladyshev
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Article
| Open Accessfhl2b mediates extraocular muscle protection in zebrafish models of muscular dystrophies and its ectopic expression ameliorates affected body muscles
Extraocular muscles remain unaffected in muscular dystrophies. Here, the authors show that the gene fhl2b has a protective role in extraocular muscle and that its protective function can be applied to rescue other muscles in a zebrafish model of muscular dystrophy.
- Nils Dennhag
- , Abraha Kahsay
- & Fatima Pedrosa Domellöf
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Article
| Open AccessA GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis
The endometrium is activated by the pregnancy hormones estrogen and progesterone to facilitate embryo implantation, and errors in endometrial responsiveness can lead to reduced fertility or endometriosis. Here they show that GREB1 interacts with hormone receptors in the endometrium, leading to normal or pathological consequences depending on the hormones involved.
- Sangappa B. Chadchan
- , Pooja Popli
- & Ramakrishna Kommagani
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Article
| Open AccessPolycomb-mediated silencing of miR-8 is required for maintenance of intestinal stemness in Drosophila melanogaster
Intestinal physiology requires a balance between stem cell self-renewal and differentiation. Here, the authors show that this balance is regulated epigenetically by a dynamic relationship between the evolutionarily conserved PRC2, miR-8 and Notch signaling.
- Zoe Veneti
- , Virginia Fasoulaki
- & Aristides G. Eliopoulos
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Article
| Open AccessDeregulated protein homeostasis constrains fetal hematopoietic stem cell pool expansion in Fanconi anemia
In this manuscript, the authors show deregulated protein synthesis as a novel, noncanonical defect in Fanconi Anemia. The observed deficits reflect the impact of proteostasis during fetal hematopoietic stem cell expansion and define the origins of hematopoietic failure in this disorder.
- Narasaiah Kovuru
- , Makiko Mochizuki-Kashio
- & Peter Kurre
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Article
| Open AccessThe emergence of circadian timekeeping in the intestine
Circadian rhythms are present in cells throughout the body but how these develop is poorly understood. Here, using Drosophila genetics and single cell analysis, authors find that the intestinal clock emerges after development is complete, and that differentiation disrupts its function.
- Kathyani Parasram
- , Amy Zuccato
- & Phillip Karpowicz
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Article
| Open AccessComparative transcriptomics coupled to developmental grading via transgenic zebrafish reporter strains identifies conserved features in neutrophil maturation
Maturation of innate immune cells is a graded stereotypic process which is often conserved across species. Here authors label distinct neutrophil leukocyte developmental stages via generating combinations of transgenic zebrafish reporter strains, followed by transcriptome analysis of different neutrophil maturation stages and comparison to the gene expression profile of developing neutrophils from humans and mice.
- Stefanie Kirchberger
- , Mohamed R. Shoeb
- & Martin Distel
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Article
| Open AccessQuiescence enables unrestricted cell fate in naive embryonic stem cells
Stem cell quiescence is generally considered as an inactive state with poised potential. Here, Khoa et al. find that quiescent embryonic stem cells actively maintain a dynamic reservoir of cells with unrestricted cell fate that converges on S-adenosylmethionine and H3K27me3 status.
- Le Tran Phuc Khoa
- , Wentao Yang
- & Yali Dou
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Article
| Open AccessCellular reprogramming in vivo initiated by SOX4 pioneer factor activity
Upon physiological injury, hepatocytes transdifferentiate into biliary epithelial cells, a process involving molecular rewiring. Here, authors show that Sox4 organizes the early steps, acting as a pioneer factor to decommission hepatocyte enhancers and open chromatin around biliary genes.
- Takeshi Katsuda
- , Jonathan H. Sussman
- & Ben Z. Stanger
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Article
| Open AccessInterplay between coding and non-coding regulation drives the Arabidopsis seed-to-seedling transition
Seed germination in plants is a tightly controlled process relying on translation of stored RNAs. Here, Tremblay et al. show that nascent transcriptome and epigenome reprogramming are detected from initial stages of germination.
- Benjamin J. M. Tremblay
- , Cristina P. Santini
- & Julia I. Qüesta
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Article
| Open AccessRunx1+ vascular smooth muscle cells are essential for hematopoietic stem and progenitor cell development in vivo
Hematopoietic stem cells are supported by niche cells that help balance stem cell self-renewal and differentiation. Here they show that Runx1 deletion in the embryonic perivascular HSC niche impairs hematopoietic development in vivo and causes transcriptional changes in pericytes/vSMCs, endothelial cells and hematopoietic cells in the murine AGM.
- Zaniah N. Gonzalez Galofre
- , Alastair M. Kilpatrick
- & Mihaela Crisan
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Article
| Open AccessJAK-STAT-dependent contact between follicle cells and the oocyte controls Drosophila anterior-posterior polarity and germline development
The authors identified a cell population in Drosophila follicles that elaborate filopodia penetrating the oocyte they are contacting. These somatic cells are essential during oogenesis to regulate polarity and germline development of the future embryo.
- Charlotte Mallart
- , Sophie Netter
- & Marianne Malartre
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Article
| Open AccessM2 macrophages independently promote beige adipogenesis via blocking adipocyte Ets1
Adipose beiging is a positive biological change, which is often thought to be primarily sympathetically induced. Here, the authors show that M2 macrophages can independently promote beige adipogenesis, further revealing the adipocyte transcription factor Ets1 as a negative regulator of this process.
- Suyang Wu
- , Chen Qiu
- & Xiao Han
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Article
| Open AccessNoncanonical function of folate through folate receptor 1 during neural tube formation
Neural tube defects are common birth defects that have been shown to be reduced through periconceptional folate supplementation, though the mechanism for this effect is unclear. Here they show that FOLR1 is necessary for neural tube formation in human neural organoids and Xenopus laevis embryos, and that this role is independent of its folate transport function.
- Olga A. Balashova
- , Alexios A. Panoutsopoulos
- & Laura N. Borodinsky
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Article
| Open AccessTREX tetramer disruption alters RNA processing necessary for corticogenesis in THOC6 Intellectual Disability Syndrome
THOC6 is required for TREX tetramer formation. Analysis of pathogenic THOC6 variants differentiate the conserved mRNA export functions of TREX dimers and RNA processing functions of TREX tetramers underlying THOC6 Intellectual Disability Syndrome.
- Elizabeth A. Werren
- , Geneva R. LaForce
- & Ashleigh E. Schaffer
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Article
| Open AccessCis inhibition of NOTCH1 through JAGGED1 sustains embryonic hematopoietic stem cell fate
Notch signaling is critical for HSC emergence. Here, the authors identify a sub-set of hemogenic endothelial cells with high Notch activity that it is gradually shut down through cis inhibition of NOTCH1 by JAG1, and report that this process sustains HSC.
- Roshana Thambyrajah
- , Maria Maqueda
- & Anna Bigas
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Article
| Open AccessSea lamprey enlightens the origin of the coupling of retinoic acid signaling to vertebrate hindbrain segmentation
Retinoic acid signaling is involved in patterning the embryonic antero-posterior axis, and also regulates hindbrain segmentation in jawed vertebrates. Here they show that retinoic acid signaling plays important roles in hindbrain segmentation in a jawless vertebrate, the lamprey, thus indicating this feature of hindbrain development is conserved in all vertebrates.
- Alice M. H. Bedois
- , Hugo J. Parker
- & Robb Krumlauf
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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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Article
| Open AccessEvolutionarily related host and microbial pathways regulate fat desaturation in C. elegans
Fatty acid desaturation is central to metazoan lipid metabolism. Here, using C. elegans as a model, the authors show that both endogenous and microbiota-dependent small molecule signals converge to promote lipid desaturation via the nuclear receptor NHR-49/PPARα.
- Bennett W. Fox
- , Maximilian J. Helf
- & Frank C. Schroeder
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Article
| Open AccessRegulation of long-range BMP gradients and embryonic polarity by propagation of local calcium-firing activity
Identical twins from a single embryo are formed in multiple species, albeit rarely. It is not clear how such twinning is suppressed during early development. Here they show that calcium signalling activity is propagated through the extraembryonic tissue to prevent ectopic primitive streak formation during gastrulation.
- Hyung Chul Lee
- , Nidia M. M. Oliveira
- & Claudio D. Stern
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Article
| Open AccessTime-integrated BMP signaling determines fate in a stem cell model for early human development
The interpretation of the key developmental signal BMP remains poorly understood. Here, the authors show that the total time-integrated signaling controls differentiation in a stem cell embryo model and provide a possible mechanism.
- Seth Teague
- , Gillian Primavera
- & Idse Heemskerk
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Article
| Open AccessPro-ferroptotic signaling promotes arterial aging via vascular smooth muscle cell senescence
Ferroptosis is a novel form of regulated cell death associated with lipid oxidation. Here, the authors demonstrate that the proferroptosis signal is activated and drives vascular aging by inducing senescence in vascular smooth muscle cells.
- Di-Yang Sun
- , Wen-Bin Wu
- & Pei Wang
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Article
| Open AccessNeurofibromin 1 controls metabolic balance and Notch-dependent quiescence of murine juvenile myogenic progenitors
The establishment of the postnatal skeletal muscle stem cell pool is not well understood. Here the authors show a requirement for Nf1 to coordinate muscle fiber growth and stem cell quiescence induction, and to prevent detrimental metabolic reprogramming with life-long consequences.
- Xiaoyan Wei
- , Angelos Rigopoulos
- & Sigmar Stricker
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Article
| Open AccessExperimental evidence for cancer resistance in a bat species
Bats have been suggested to be resistant to cancer due to mechanisms related to their evolved longevity, but the associated molecular drivers are still understudied. Here, the authors examine cancer resistance mechanisms across seven bat species using in vitro and in vivo models, and identify HIF1A, COPS5, and RPS3 as related genes.
- Rong Hua
- , Yuan-Shuo Ma
- & Zhen Liu
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Article
| Open AccessIn vitro induction of patterned branchial arch-like aggregate from human pluripotent stem cells
Early patterning of neural crest cells in the craniofacial primordium is important for its subsequent development. Here, authors establish in vitro model of branchial arch from human pluripotent stem cells for determining underlying mechanisms.
- Yusuke Seto
- , Ryoma Ogihara
- & Mototsugu Eiraku
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Article
| Open AccessUltrastructure of macromolecular assemblies contributing to bacterial spore resistance revealed by in situ cryo-electron tomography
Bacterial endospores are among the most resilient forms of life. Here, authors reveal ultrastructural details of the spore chromosome and the multiprotein, multilayered extracellular coat, shedding light on mechanisms contributing to spore resistance.
- Elda Bauda
- , Benoit Gallet
- & Cecile Morlot
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Article
| Open AccessNutrient-dependent regulation of a stable intron modulates germline mitochondrial quality control
The quality of germline mitochondria is essential for producing healthy oocytes. Here, Ng, Chan and Pek report a stable intron that modulates germline mitochondrial quality control during fasting, heat stress and aging.
- Annabel Qi En Ng
- , Seow Neng Chan
- & Jun Wei Pek
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Article
| Open AccessMatrin3 mediates differentiation through stabilizing chromatin loop-domain interactions and YY1 mediated enhancer-promoter interactions
Alterations in proteins within nuclear compartments often lead to changes in chromosomal architecture. Here, using acute targeted protein degradation, the authors reveal that the nuclear complex protein Matrin3 directly mediates differentiation through stabilizing chromatin loop domain interactions.
- Tianxin Liu
- , Qian Zhu
- & Stuart H. Orkin
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Article
| Open AccessDiffusible fraction of niche BMP ligand safeguards stem-cell differentiation
The activity of Drosophila male germline stem cells is tightly regulated by a cluster of somatic niche cells. Here they find that Dpp induces opposed cellular responses in stem cells versus in differentiating descendants, thereby ensuring spatial control of the niche with a single factor.
- Sharif M. Ridwan
- , Autumn Twillie
- & Mayu Inaba
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Article
| Open AccessShort-term periodic restricted feeding elicits metabolome-microbiome signatures with sex dimorphic persistence in primate intervention
Here, the authors show that periodic restricted feeding (PRF) in Rhesus monkeys induces lasting weight loss not directly tied to reduced calories, while altering sex-specific metabolome and microbiome composition, in turn associated with long-term benefits.
- Hagai Yanai
- , Bongsoo Park
- & Isabel Beerman
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Article
| Open Access5-aminosalicylic acid suppresses osteoarthritis through the OSCAR-PPARγ axis
There is a strong need for the development of effective and safe disease-modifying osteoarthritis drugs. Here, the authors show that 5-ASA, an anti-inflammatory drug used for ulcerative colitis, shows promise in treating osteoarthritis in mice by improving cartilage and reducing inflammation even when administered at late stages of disease.
- Jihee Kim
- , Gina Ryu
- & Soo Young Lee
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Article
| Open AccessR-Spondin 2 governs Xenopus left-right body axis formation by establishing an FGF signaling gradient
Left-right (LR) body asymmetry is established by leftward flow in the LR organizer. Here, the authors show in Xenopus that R-Spondin 2 acts as an FGF receptor antagonist that produces a right-to-left FGF signaling gradient in response to flow to break LR symmetry.
- Hyeyoon Lee
- , Celine Marie Camuto
- & Christof Niehrs
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Matters Arising
| Open AccessReply to: Assessing the precision of morphogen gradients in neural tube development
- Roman Vetter
- & Dagmar Iber
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Matters Arising
| Open AccessAssessing the precision of morphogen gradients in neural tube development
- Marcin Zagorski
- , Nathalie Brandenberg
- & Anna Kicheva
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Article
| Open AccessTissue-specific profiling of age-dependent miRNAomic changes in Caenorhabditis elegans
Wang et al. profile age-dependent miRNAomic changes in worm tissues and extracellular vesicles (EVs). They show that ageing controls miRNAs in a tissue-specific manner and their findings further suggest a complex EV-mediated miRNA trafficking network across tissues.
- Xueqing Wang
- , Quanlong Jiang
- & Yidong Shen
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Article
| Open AccessRan-GTP assembles a specialized spindle structure for accurate chromosome segregation in medaka early embryos
Mitotic spindle assembles in each blastomere to segregate duplicated chromosomes during cleavage of the fertilized egg. Here, the authors establish functional assays in fish embryos and find that Ran-GTP assembles a microtubule network at the metaphase spindle center that is essential for chromosome segregation.
- Ai Kiyomitsu
- , Toshiya Nishimura
- & Tomomi Kiyomitsu
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Article
| Open AccessHRDE-2 drives small RNA specificity for the nuclear Argonaute protein HRDE-1
Argonaute proteins are loaded with small RNAs to confer target RNA specificity and proper gene silencing. Here, the authors establish that HRDE-2 recruits the unloaded nuclear Argonaute HRDE-1 to germ granules to facilitate correct small RNA loading.
- Shihui Chen
- & Carolyn M. Phillips
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Article
| Open AccessUbiquitin ligase RNF20 coordinates sequential adipose thermogenesis with brown and beige fat-specific substrates
Upon cold exposure, two types of thermogenic fat cells, brown and beige adipocytes, are sequentially activated. Here, the authors show that E3 ubiquitin ligase RNF20 coordinates the sequential thermogenic activation through fat depot specific substrates.
- Yong Geun Jeon
- , Hahn Nahmgoong
- & Jae Bum Kim
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Article
| Open AccessRNA polymerase II pausing is essential during spermatogenesis for appropriate gene expression and completion of meiosis
Gene expression dynamics are tightly regulated during spermatogenesis, with disruptions resulting in infertility. Here they identify a critical role for RNA PolII pausing in spermatogenesis and show that loss of the RNA PolII pausing factor NELF causes meiotic arrest.
- Emily G. Kaye
- , Kavyashree Basavaraju
- & Prabhakara P. Reddi
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Article
| Open AccessSingle-cell multiomics decodes regulatory programs for mouse secondary palate development
Development of the secondary palate is a complex process. Here, the authors profile mouse palatogenesis through single-cell multiome sequencing, revealing dynamic gene regulation across embryonic days (E) 12.5, E13.5, E14.0, and E14.5.
- Fangfang Yan
- , Akiko Suzuki
- & Zhongming Zhao
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Article
| Open AccessCebp1 and Cebpβ transcriptional axis controls eosinophilopoiesis in zebrafish
Eosinophils are innate immune cells critical for protection from parasites, but their developmental origin remains under studied. Here they analyze development of eosinophils in zebrafish and find that eosinophilic lineage commitment and differentiation are regulated by the Cebp1-Cebpβ axis.
- Gaofei Li
- , Yicong Sun
- & Yiyue Zhang
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Article
| Open AccessChemically-defined and scalable culture system for intestinal stem cells derived from human intestinal organoids
Challenges in reproducibility and large-scale expansion limit the current applicability of human intestinal organoids. Here, the authors present a feeder-free, chemically-defined culture method for enrichment of intestinal stem cells isolated from 3D human intestinal organoids.
- Ohman Kwon
- , Hana Lee
- & Mi-Young Son
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Article
| 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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Article
| Open AccessEmergence of periodic circumferential actin cables from the anisotropic fusion of actin nanoclusters during tubulogenesis
Periodic circumferential cytoskeletons support biological tube formation. Here, the authors show that self-assembled actin nanoclusters undergo biased fusion and develop into periodic cables in response to the membrane anisotropy of the expanding Drosophila tracheal tube.
- Sayaka Sekine
- , Mitsusuke Tarama
- & Shigeo Hayashi
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Article
| Open AccessAn IL-10/DEL-1 axis supports granulopoiesis and survival from sepsis in early life
Neutrophils play critical roles in response to infection, and the limit of available neutrophils in neonates and young infants can impact responses to infections, including sepsis. Here the authors identify that the IL-10/DEL-1 axis is involved in emergency granulopoiesis in neonates and suggest a link to sepsis survival in early life.
- Eleni Vergadi
- , Ourania Kolliniati
- & Christos Tsatsanis
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Article
| 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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Article
| Open AccessSox9 regulates alternative splicing and pancreatic beta cell function
Sox9 is a well-known transcriptional regulator of embryonic pancreas and endocrine cell development. Here, the authors show that loss of Sox9 in mature beta cells disrupts alternative splicing patterns and impairs insulin secretion, with significant implications for cellular function.
- Sapna Puri
- , Hasna Maachi
- & Matthias Hebrok
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Article
| Open AccessEmbryos assist morphogenesis of others through calcium and ATP signaling mechanisms in collective teratogen resistance
The collective activity of cells enables embryos to overcome various perturbations. Here, authors show that at the higher (population) level, embryos also communicate. This enables larger groups to resist chemical and molecular-genetic teratogens.
- Angela Tung
- , Megan M. Sperry
- & Michael Levin
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Article
| Open AccessVGLL1 cooperates with TEAD4 to control human trophectoderm lineage specification
Authors report that VGLL1 regulates cell fate determination and self-renewal of human pluripotent stem cell-derived trophectoderm-like cells and trophoblast stem cells via modulation of chromatin accessibility in cooperation with TEAD4.
- Yueli Yang
- , Wenqi Jia
- & Wenjuan Li
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