Featured
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Article
| Open AccessSOXC are critical regulators of adult bone mass
Angelozzi et al. uncover key mechanisms involved in physiological and pathological bone mass remodeling by showing that SOXC transcription factors regulate the bone formation and resorption balance via critical roles in LepR+ mesenchymal stem cells.
- Marco Angelozzi
- , Anirudha Karvande
- & Véronique Lefebvre
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Article
| Open AccessTwo orthogonal differentiation gradients locally coordinate fruit morphogenesis
The coordination of cellular behaviors is essential for proper organogenesis. Here the authors show that fruit development in Arabidopsis is governed by time-shifted differentiation gradients that act locally along two perpendicular organ axes.
- Andrea Gómez-Felipe
- , Elvis Branchini
- & Daniel Kierzkowski
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Article
| Open AccessEph-ephrin signaling couples endothelial cell sorting and arterial specification
Arteries are vital blood vessels for our body and their growth and patterning are critical for proper blood flow. Here they use a retina model to show that a balance of EphB4 receptor and ephrin-B2 ligand integrate a well-wired molecular network to control arteriovenous patterning and vascular growth.
- Jonas Stewen
- , Kai Kruse
- & Mara E. Pitulescu
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Article
| Open AccessAge-progressive interplay of HSP-proteostasis, ECM-cell junctions and biomechanics ensures C. elegans astroglial architecture
Neural circuit architecture must be maintained during an animal’s lifetime. Here, the authors show that a protective mechanism combining proteostasis and biomechanics supports the integrity of glial cells to environmental stressors.
- Francesca Coraggio
- , Mahak Bhushan
- & Georgia Rapti
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Article
| 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 AccessA conserved NR5A1-responsive enhancer regulates SRY in testis-determination
Disease-causing variants define a conserved and unique NR5A1 responsive enhancer for SRY expression to initiate testis-determination in humans. Modelling regulatory variants causing sex-reversal provides a tool to understand global enhancer activity.
- Denis Houzelstein
- , Caroline Eozenou
- & Ken McElreavey
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Article
| Open AccessTransient expression of the neuropeptide galanin modulates peripheral‑to‑central connectivity in the somatosensory thalamus during whisker development in mice
The function of transient neuropeptides in developmental roles in the nervous system remains elusive. Here, authors demonstrate that galanin shapes synaptic wiring in the whisker pathway, a fundamental sensory modality for infant rodents before eye opening.
- Zsofia Hevesi
- , Joanne Bakker
- & Tibor Harkany
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Article
| Open AccessGene-expression memory-based prediction of cell lineages from scRNA-seq datasets
Combining experimental lineage tracing with single cell transcriptomics is technically demanding. Here, authors present GEMLI, a computational tool to annotate cell lineages in single cell RNA sequencing data solely based on gene expression.
- A. S. Eisele
- , M. Tarbier
- & D. M. Suter
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Article
| Open AccessMapping cell-to-tissue graphs across human placenta histology whole slide images using deep learning with HAPPY
Placenta histopathology for maternal and newborn health is highly specialised and time consuming. Here, authors present a deep learning pipeline for quantifying cells and tissues in placenta whole slide images, revealing biological and clinical insights.
- Claudia Vanea
- , Jelisaveta Džigurski
- & Christoffer Nellåker
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Article
| Open AccessPheromone-based communication influences the production of somatic extracellular vesicles in C. elegans
Extracellular vesicles are fundamental in cellular communication. Here, authors show how C. elegans pheromones regulate vesicle production, showcasing the impact of social behaviors on cellular mechanisms.
- Agata Szczepańska
- , Katarzyna Olek
- & Michał Turek
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Article
| Open AccessCondensin-mediated restriction of retrotransposable elements facilitates brain development in Drosophila melanogaster
Mutations in condensin subunits cause microcephaly, but the underlying molecular mechanisms remain elusive. Here, the authors show that unrestricted retrotransposable element activity impairs brain development in condensin insufficient organisms.
- Bert I. Crawford
- , Mary Jo Talley
- & Michelle S. Longworth
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Review Article
| Open AccessDevelopmental timing in plants
Plants exhibit reproducible timing of developmental events at multiple scales, from switches in cell identity to maturation of the whole plant. Using simplified models to convey key concepts, we review how timing mechanisms interact with the environment to control cyclical and progressive developmental transitions.
- Enrico Coen
- & Przemyslaw Prusinkiewicz
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Article
| Open AccessCell-fate conversion of intestinal cells in adult Drosophila midgut by depleting a single transcription factor
The mechanisms underlying cell plasticity remain poorly understood. Here, Guo et.al discover that intestinal cells in the fly gut can alter their fates through the loss of a single gene, and identify several molecular barriers to cell reprogramming.
- Xingting Guo
- , Chenhui Wang
- & Rongwen Xi
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Article
| Open AccessThe level of protein in the maternal murine diet modulates the facial appearance of the offspring via mTORC1 signaling
Children’s faces resemble their parents to various degrees. Here they show that the maternal diet affects the facial appearances of newborns and that inherited and adaptive mechanisms sculpturing facial bones are linked via dietary protein levels and the mTOR signaling pathway.
- Meng Xie
- , Markéta Kaiser
- & Andrei S. Chagin
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Article
| Open AccessA let-7 microRNA-RALB axis links the immune properties of iPSC-derived megakaryocytes with platelet producibility
The authors pioneered the iPSC-derived platelet transfusion in human. Here they employ miRNA switches, identifying RALB as a determinant of immune megakaryocytes and a marker for quality control, advancing standardization of iPSC-platelet production.
- Si Jing Chen
- , Kazuya Hashimoto
- & Koji Eto
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Article
| Open Accessp53 regulates diverse tissue-specific outcomes to endogenous DNA damage in mice
DNA repair deficiency can cause tissue-specific phenotypes in humans and mice. Here, the authors find that p53 drives different, but tissue-specific responses despite the same defect in DNA repair. p53 drives blood stem cell loss but restrains liver polyploidisation in the absence of Ercc1.
- Ross J. Hill
- , Nazareno Bona
- & Gerry P. Crossan
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Article
| Open AccessOsteocyte mitochondria regulate angiogenesis of transcortical vessels
Osteocytes are the key cellular components of cortical bone. Here they show that osteocytes transfer mitochondria to the endothelial cells of transcortical vessels (TCVs), which promotes angiogenesis and increases function of the TCV network.
- Peng Liao
- , Long Chen
- & Junjie Gao
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Article
| Open AccessAn evolutionary mechanism to assimilate new nutrient sensors into the mTORC1 pathway
Unmet expectations, a previously uncharacterized fly protein, is a SAM sensor for the mTORC1 pathway. Tracing the evolution of Unmet reveals that the pathway uses the GATOR2 complex to capture and repurpose ancestral enzymes as nutrient sensors.
- Grace Y. Liu
- , Patrick Jouandin
- & David M. Sabatini
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Article
| Open AccessTgfbr1 controls developmental plasticity between the hindlimb and external genitalia by remodeling their regulatory landscape
Development of hindlimbs and external genitalia share several regulatory factors. Lozovska et al. show that Tgfbr1 controls the response to those factors; embryos lacking Tgfbr1 develop two sets of hindlimbs at the expense of the external genitalia.
- Anastasiia Lozovska
- , Artemis G. Korovesi
- & Moisés Mallo
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Article
| Open AccessHeterozygous missense variant in GLI2 impairs human endocrine pancreas development
Mutations in the Hedgehog signaling have not been previously associated to diabetes. Here, authors identify a missense variant of GLI2 in a family with early-onset diabetes and report an essential role of this gene during human iPSC-based pancreatic differentiation.
- Laura M. Mueller
- , Abigail Isaacson
- & Francesca M. Spagnoli
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Article
| Open AccessBalancing competing effects of tissue growth and cytoskeletal regulation during Drosophila wing disc development
The authors integrate computational and quantitative approaches to elucidate how organ shape arises through the interplay between multiple growth pathways through regulation of both proliferation and the cytoskeleton.
- Nilay Kumar
- , Jennifer Rangel Ambriz
- & Mark Alber
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Article
| Open AccessSingle cell atlas of Xenoturbella bocki highlights limited cell-type complexity
Recent phylogenetic analyses have identified orphan clades, including Xenacoelomorphs, that can offer insights into bilaterian evolution. Here they generate a cell type atlas of Xenoturbella bockithat highlights cellular diversity in the nervous system and other tissues, reinforcing the idea of parallel evolution of cell types across animals.
- Helen E. Robertson
- , Arnau Sebé-Pedrós
- & Heather Marlow
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Article
| Open AccessEvolutionary origin of Hoxc13-dependent skin appendages in amphibians
Hair is the main skin appendage of mammals. Here, the authors show that claws of clawed frogs and hair contain homologous keratins and depend on the same transcription factor, Hoxc13, suggesting a common evolutionary origin of these skin appendages.
- Marjolein Carron
- , Attila Placido Sachslehner
- & Leopold Eckhart
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Article
| Open AccessHepatic nutrient and hormone signaling to mTORC1 instructs the postnatal metabolic zonation of the liver
The liver is segregated into spatially organized areas that serve distinct functions, though how these zones are patterned remains unclear. Here they show that mTORC1 controls spatial segregation of liver metabolic functions via modulation of Wnt signaling, and find that impaired zonation is also observed in pigs given total parenteral nutrition.
- Ana Belén Plata-Gómez
- , Lucía de Prado-Rivas
- & Alejo Efeyan
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Article
| Open AccessTemporospatial hierarchy and allele-specific expression of zygotic genome activation revealed by distant interspecific urochordate hybrids
Wei et al. report a unique interspecific ascidian hybrid system and single-cell RNA sequencing to reveal the temporal hierarchy, spatial heterogeneity, and allele-specific expression of zygotic genome activation in urochordates.
- Jiankai Wei
- , Wei Zhang
- & Bo Dong
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Article
| Open AccessAutophagy regulates the maturation of hematopoietic precursors in the embryo
The production of hematopoietic stem cells in the embryo is precisely regulated by various intrinsic and extrinsic factors. Here, the authors find that autophagy is involved in the maturation of hematopoietic precursors through nucleolin pathways.
- Yumin Liu
- , Linjuan Shi
- & Zhuan Li
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Article
| Open AccessTANGO6 regulates cell proliferation via COPI vesicle-mediated RPB2 nuclear entry
How RNA polymerase II subunits enter the nucleus is not well understood. Here, the authors show that Transport and Golgi organization protein 6, TANGO6, recruits RNA polymerase II subunit B2, RPB2, to the ER membrane in a retrograde manner and transports it to the nucleus with the aid of importins.
- Zhi Feng
- , Shengnan Liu
- & Li Li
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Article
| Open AccessSpatiotemporal formation of glands in plants is modulated by MYB-like transcription factors
The spatiotemporal formation of glands in tomato trichomes is regulated by two MYB-like transcription factors, named as GCR1 and 2, whose expression is tightly restricted by SlTOE1B. GCR1 and 2 inhibit gland formation by repressing LFS expression.
- Jiang Chang
- , Shurong Wu
- & Shuang Wu
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Article
| Open AccessSuppression of apoptosis impairs phalangeal joint formation in the pathogenesis of brachydactyly type A1
Authors explore the biological mechanisms underlying a missing digit joint in Brachydactyly type A1. They showed that excess Indian Hedgehog proteins suppress the apoptosis level needed for the progression of digit joint development in a mouse model.
- Adrian On Wah Leung
- , Andrew Chung Hin Poon
- & Danny Chan
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Article
| Open AccessDynamic enhancer landscapes in human craniofacial development
Rajderkar et al. provide a genome-wide compendium of transcriptional enhancers active in human craniofacial development, along with single-cell resources for studies of mammalian craniofacial morphogenesis.
- Sudha Sunil Rajderkar
- , Kitt Paraiso
- & Axel Visel
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Article
| Open AccessA single-cell atlas of Drosophila trachea reveals glycosylation-mediated Notch signaling in cell fate specification
Studying Drosophila trachea development can inform the mechanisms of growth of all tubular structures. Here, the authors generate a transcriptomic cell atlas of the developing fly trachea and establish roles for Notch signaling, which may be disrupted by diet-induced glycosylation.
- Yue Li
- , Tianfeng Lu
- & Hai Huang
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Article
| Open AccessKey homeobox transcription factors regulate the development of the firefly’s adult light organ and bioluminescence
Adult firefly light organs exhibit flashing signals important for courtship, though how these organs form during development is largely unknown. Here the authors demonstrate that homeobox transcription factors play a patterning role in the development of the adult light organs.
- Xinhua Fu
- & Xinlei Zhu
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Article
| Open AccessEndothelial cells regulate alveolar morphogenesis by constructing basement membranes acting as a scaffold for myofibroblasts
During alveologenesis myofibroblasts contractions at terminal sacs produce alveoli in the lungs. Here they show that endothelial cells promote myofibroblast-driven alveologenesis by forming basement membranes via Rap1-induced integrin β1 activation.
- Haruko Watanabe-Takano
- , Katsuhiro Kato
- & Shigetomo Fukuhara
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Article
| Open AccessExtensive DNA methylome rearrangement during early lamprey embryogenesis
DNA methylation plays a major role in establishing cell identity, but the dynamics of DNA methylation patterns are highly variable across species. Here, the authors discover extensive DNA methylation reprogramming during embryonic development of the sea lamprey, a jawless fish with a distinctive, highly disordered methylome.
- Allegra Angeloni
- , Skye Fissette
- & Ozren Bogdanovic
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Article
| Open AccessNotch2 controls developmental fate choices between germinal center and marginal zone B cells upon immunization
Sustained exogenous Notch2 signaling prompts Follicular B cells to trans-differentiate into Marginal Zone B cells. This study reveals that under physiological conditions, Notch2 signalling regulates a fate choice in antigen activated Follicular B cells, dictating whether they develop into Germinal Center B cells or Marginal Zone B cells.
- Tea Babushku
- , Markus Lechner
- & Lothar J. Strobl
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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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