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Mechanical control of neural plate folding by apical domain alteration
Theoretical and experimental observations argue that apical domain heterogeneity in the neural plate is a tug-of-war contest between constricted and elongated cells. This competition likely reflects mechanical forces operating during tissue bending.
- Miho Matsuda
- , Jan Rozman
- & Sergei Y. Sokol
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KDM2B regulates hippocampal morphogenesis by transcriptionally silencing Wnt signaling in neural progenitors
Zhang et al. report that KDM2B-∆CxxC activated Wnt signaling in the developing hippocampi, where the migration and differentiation of neural progenitors were blocked. KDM2B-∆CxxC mice exhibited defects of hippocampal morphology and related behaviors.
- Bo Zhang
- , Chen Zhao
- & Yan Zhou
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Non-uniform temporal scaling of developmental processes in the mammalian cortex
Marsupial mammals take much longer to develop than similarly sized placental mammals, though how brain development occurs across these different periods is unclear. Here they show that the neurodevelopmental events of cortical neurogenesis, cell migration and axon extension do not all temporally scale to the same extent.
- Annalisa Paolino
- , Elizabeth H. Haines
- & Laura R. Fenlon
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SNIP1 and PRC2 coordinate cell fates of neural progenitors during brain development
The balance of stem cell maintenance, differentiation, and programmed death is critical for proper development. Here they show that SNIP1 is critical for stem cell survival and differentiation in the developing brain where it acts downstream of TGFb and NFkB and regulates PRC2 activities for governing cell fates.
- Yurika Matsui
- , Mohamed Nadhir Djekidel
- & Jamy C. Peng
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Spatiotemporal proteomic atlas of multiple brain regions across early fetal to neonatal stages in cynomolgus monkey
Proteomic data covering fetal and neonatal primate brain development in the primate brain is needed to understand development and changes in functional gene products. Here, the authors show the dynamic proteomic changes of the cynomolgus macaque brain during the development from early fetal to neonatal stages by constructing a spatiotemporal proteomic atlas.
- Jingkuan Wei
- , Shaoxing Dai
- & Wei Si
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Asymmetric activity of NetrinB controls laterality of the Drosophila brain
Brain asymmetry is widespread across species, but its function remains poorly understood. Here, the authors show that the Netrin axon guidance pathway is involved in building an asymmetric neural circuit important for long-term memory in Drosophila.
- F. Lapraz
- , C. Boutres
- & S. Noselli
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Redox-dependent Igfbp2 signaling controls Brca1 DNA damage response to govern neural stem cell fate
How reactive oxygen species regulate neuronal stem cell (NSC) behavior is poorly understood. Here, the authors report that Ncf1-dependent oxidation of Igfbp2 cystines represses DNA repair networks to regulate NSC self-renewal and cell fate decisions.
- Weam S. Shahin
- , Shima O. Ebed
- & John F. Engelhardt
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CBP-HSF2 structural and functional interplay in Rubinstein-Taybi neurodevelopmental disorder
Rubinstein-Taybi syndrome (RSTS) is a neurodevelopmental disorder with unclear underlying mechanisms. Here, the authors unravel the contribution of a stress-responsive pathway to RSTS where impaired HSF2 acetylation, due to RSTS-associated CBP/EP300 mutations, alters the expression of neurodevelopmental players, in keeping with hallmarks of cell-cell adhesion defects.
- Aurélie de Thonel
- , Johanna K. Ahlskog
- & Valérie Mezger
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MTG8 interacts with LHX6 to specify cortical interneuron subtype identity
There is a large diversity of inhibitory interneurons in the mammalian cerebral cortex. How this emerges during embryogenesis remains unclear. Here, the authors identify MTG8 as a co-factor of LHX6 and a new regulator of cortical interneuron development.
- Zeinab Asgarian
- , Marcio Guiomar Oliveira
- & Nicoletta Kessaris
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Wireless charging-mediated angiogenesis and nerve repair by adaptable microporous hydrogels from conductive building blocks
Traumatic brain injury can cause long-term disability and thus constitutes a substantial healthcare burden worldwide. Here, the authors report a conductive microporous hydrogel to improve angiogenesis and recovery of brain function in traumatic brain lesions.
- Ru-Siou Hsu
- , Ssu-Ju Li
- & Shang-Hsiu Hu
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Spatiotemporal single-cell regulatory atlas reveals neural crest lineage diversification and cellular function during tooth morphogenesis
The mechanisms that govern cell fate decisions of postmigratory cranial neural crest cells remain largely unknown. Here the authors present a spatiotemporal single-cell regulatory atlas tracking these cells’ dental lineage diversification.
- Junjun Jing
- , Jifan Feng
- & Yang Chai
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An epigenome atlas of neural progenitors within the embryonic mouse forebrain
The authors took a multimodal approach to characterize the differential transcriptome and epigenetic landscape between distinct regions of the embryonic mouse forebrain, revealing many unexplored presumptive promoter-enhancer interactions.
- Christopher T. Rhodes
- , Joyce J. Thompson
- & Timothy J. Petros
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Robust derivation of transplantable dopamine neurons from human pluripotent stem cells by timed retinoic acid delivery
Stem cell based replacement therapies could provide a treatment for Parkinson’s disease. Here the authors outline a retinoic acid-based approach for robust derivation of dopamine neurons from stem cells that restore motor deficits in parkinsonian rats.
- Zhanna Alekseenko
- , José M. Dias
- & Johan Ericson
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Novel role of the synaptic scaffold protein Dlgap4 in ventricular surface integrity and neuronal migration during cortical development
The Dlgap protein family members are known for their role in synapses. Here the authors reveal important involvement in earlier steps of brain development, identifying DLGAP4 mutations in patients with cortical malformations, and also demonstrating a role in progenitors and migrating neurons.
- Delfina M. Romero
- , Karine Poirier
- & Fiona Francis
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Neuroligin-mediated neurodevelopmental defects are induced by mitochondrial dysfunction and prevented by lutein in C. elegans
Mitochondrial deficiency causes rare incurable disorders. Here, the authors use C. elegans to study these diseases and find that the natural compound lutein prevents neurodevelopmental deficits, thus pointing to a possible therapeutic target for the human diseases.
- Silvia Maglioni
- , Alfonso Schiavi
- & Natascia Ventura
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A comprehensive temporal patterning gene network in Drosophila medulla neuroblasts revealed by single-cell RNA sequencing
During development, neural progenitors generate a variety of neural types sequentially. Here the authors examine gene expression patterns in Drosophila neural progenitors at single-cell level, and identify a gene regulatory network controlling the sequential generation of different neural types.
- Hailun Zhu
- , Sihai Dave Zhao
- & Xin Li
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Precision of morphogen gradients in neural tube development
Morphogen gradients encode positional information during development. Here the authors use theory and simulations to suggest a positional accuracy of single gradients that directly explains the observed precision of progenitor domain boundaries.
- Roman Vetter
- & Dagmar Iber
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The histone demethylase Kdm6b regulates subtype diversification of mouse spinal motor neurons during development
Neural cell type diversification during development is a complex and highly regulated process. Here, the authors show that the histone H3-lysine 27 demethylase Kdm6b promotes and inhibits the generation of specific motor neuron subtypes during the development of the mouse spinal cord.
- Wenxian Wang
- , Hyeyoung Cho
- & Soo-Kyung Lee
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Selective translation of epigenetic modifiers affects the temporal pattern and differentiation of neural stem cells
The temporal development of tissues and organs may be defined by the genome-wide epigenetic and transcriptional state functioning as the clock. Here the authors found that Fbl, a ribosomal RNA methyltransferase, potentially behaves as a clock during neural stem cell (NSC) development by controlling translational efficiencies of epigenetic modifiers in the cerebral cortex primordium.
- Quan Wu
- , Yuichi Shichino
- & Fumio Matsuzaki
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Transcriptional programs regulating neuronal differentiation are disrupted in DLG2 knockout human embryonic stem cells and enriched for schizophrenia and related disorders risk variants
Coordinated programs of gene expression drive brain development. Here, the authors use human embryonic stem cells and foetal cortical tissue as well as available GWAS statistics and analysis of genetic variants associated with neuropsychiatric disorders and cognition revealing a convergence on transcriptional programs regulating excitatory cortical neurogenesis.
- Bret Sanders
- , Daniel D’Andrea
- & Eunju Shin
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Identification of a modular super-enhancer in murine retinal development
Super-enhancers are regions of genomic DNA comprised of multiple putative enhancers that contribute to dynamic gene expression patterns during development. Here the authors identify a modular super-enhancer in murine retinal development and show that distinct modules are responsible for retinal progenitor cell proliferation during early and bipolar neuron genesis during late retinal development.
- Victoria Honnell
- , Jackie L. Norrie
- & Michael A. Dyer
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Temperature sensitivity of Notch signaling underlies species-specific developmental plasticity and robustness in amniote brains
Ambient temperature significantly affects embryogenesis, but adaptive molecular mechanisms that respond to temperature remain unclear. Here, the authors identified species-specific thermal sensitivity of Notch signaling in developing amniote brains.
- Tadashi Nomura
- , Kohjiro Nagao
- & Katsuhiko Ono
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Endosomal trafficking defects alter neural progenitor proliferation and cause microcephaly
Mutations in the human WDR81 gene result in severe microcephaly. Carpentieri et al. show that mutation of WDR81, a gene coding for an endosomal regulator, alters intracellular processing of the EGF receptor, leading to reduced proliferation rates of neuronal progenitors and to microcephaly.
- Jacopo A. Carpentieri
- , Amandine Di Cicco
- & Alexandre D. Baffet
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Elp2 mutations perturb the epitranscriptome and lead to a complex neurodevelopmental phenotype
Subunits of the Elongator complex have been implicated in several nervous system pathologies. Here, the authors identify ELP2 variants in six patients with neurodevelopmental anomalies and show in mouse models that these variants impact protein stability and the activity of the complex during brain development.
- Marija Kojic
- , Tomasz Gawda
- & Brandon J. Wainwright
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Intracellular trafficking of Notch orchestrates temporal dynamics of Notch activity in the fly brain
During Drosophila development, two peaks of Notch activity propagate across the neuroepithelium to generate neuroblasts. Here, the authors show Notch cis-inhibition under the control of intracellular Notch trafficking establishes these two peaks, which temporally control neurogenesis in the brain.
- Miaoxing Wang
- , Xujun Han
- & Makoto Sato
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Single-cell transcriptomic reveals molecular diversity and developmental heterogeneity of human stem cell-derived oligodendrocyte lineage cells
Brain myelinating oligodendrocytes are rare and difficult to isolate, which has limited data on their development. Here the authors develop a reporter for scalable purification of human pluripotent stem cell derived oligodendrocyte lineage cells, and use this to map differentiation using single cell RNA-sequencing,
- Xitiz Chamling
- , Alyssa Kallman
- & Donald J. Zack
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STRAP regulates alternative splicing fidelity during lineage commitment of mouse embryonic stem cells
STRAP (serine threonine kinase receptor-associated protein) promotes tumorigenicity. Here the authors report that STRAP associates with spliceosome and regulates alternative splicing during embryonic stem cell lineage commitment and early mouse embryo organogenesis.
- Lin Jin
- , Yunjia Chen
- & Pran K. Datta
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ABHD4-dependent developmental anoikis safeguards the embryonic brain
During embryonic development, neural progenitor cells undergo numerous cell divisions. Here, the authors show that ABHD4-mediated developmental anoikis distinguishes the physiological delamination and the pathological detachment of progenitor cells with relevance to fetal alcohol-induced apoptosis.
- Zsófia I. László
- , Zsolt Lele
- & István Katona
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Single cell RNA sequencing identifies early diversity of sensory neurons forming via bi-potential intermediates
The diversity of primary sensory neurons and how fate choice is determined is unclear. Here, the authors use single cell RNA sequencing analysis of early murine somatosensory neurons to show that sensory neuron diversity is achieved by a transition through a bi-potential intermediate state.
- Louis Faure
- , Yiqiao Wang
- & Saida Hadjab
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CTCF-mediated chromatin looping in EGR2 regulation and SUZ12 recruitment critical for peripheral myelination and repair
Myelination by Schwann cells (SC) in the peripheral nervous system is essential for motor function, and dysregulation of SC myelination can lead to various neuropathies. Here the authors describe a critical role of CCCTC-binding factor (CTCF)-dependent chromatin reorganization in peripheral myelination and myelin regeneration after injury.
- Jincheng Wang
- , Jiajia Wang
- & Q. Richard Lu
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Dscam1 establishes the columnar units through lineage-dependent repulsion between sister neurons in the fly brain
Columns are the functional and morphological unit of the brain, but how neurons assemble into this structure was unclear. Here, the authors show that Dscam gene rewires neurons that derive from the same stem cell to establish columns through the process of lineage-dependent repulsion.
- Chuyan Liu
- , Olena Trush
- & Makoto Sato
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Ybx1 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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Cellular and molecular properties of neural progenitors in the developing mammalian hypothalamus
The hypothalamus performs a wide range of vital physiological functions, including growth and reproductive behaviors, and circadian rhythms. The authors identify and characterize hypothalamic radial glial and hypothalamic mantle zone radial glial cells as the neural progenitors in the hypothalamus.
- Xin Zhou
- , Suijuan Zhong
- & Xiaoqun Wang
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Developmental GABA polarity switch and neuronal plasticity in Bioengineered Neuronal Organoids
Brain organoids are important tools to study early development and disease but little is known of their network activity and plasticity. Here the authors generate iPSC-derived neuronal organoids that display early network formation and maturation with evidence for a GABA polarity switch and long-term potentiation.
- Maria-Patapia Zafeiriou
- , Guobin Bao
- & Wolfram-Hubertus Zimmermann
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ADNP promotes neural differentiation by modulating Wnt/β-catenin signaling
ADNP has been connected to neural developmental disorders. Here, the authors uncover a role for ADNP in neural induction and differentiation via β-Catenin stabilization, with ADNP disruption in zebrafish leading to defective neurogenesis and decreased Wnt signaling.
- Xiaoyun Sun
- , Xixia Peng
- & Yuhua Sun
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Methylglyoxal couples metabolic and translational control of Notch signalling in mammalian neural stem cells
Gene regulation and metabolism co-ordinate self-renewal and differentiation of neural precursors (NPCs) in the developing brain. Here the authors show that methylglyoxal, a glycolytic intermediate metabolite, promotes GADPH-dependent translational repression of Notch1, thereby promoting NPC differentiation.
- Deivid Carvalho Rodrigues
- , Emily M. Harvey
- & Guang Yang
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Glial type specific regulation of CNS angiogenesis by HIFα-activated different signaling pathways
In the central nervous system, the maturation of glial cells is temporally and functionally coupled with that of the vascular network during postnatal development. Here the authors show that oligodendroglial HIFα regulates CNS angiogenesis through Wnt-independent and VEGF-dependent signaling, while astroglial HIFα participates through Wnt-dependent signaling.
- Sheng Zhang
- , Bokyung Kim
- & Fuzheng Guo
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Transient microglial absence assists postmigratory cortical neurons in proper differentiation
Microglia temporarily disappear from the cortical plate in the midembryonic stage. This study demonstrated that microglial transient absence from the cortical plate is required for postmigratory neurons to appropriately fine-tune the expression of molecules needed for their proper differentiation.
- Yuki Hattori
- , Yu Naito
- & Takaki Miyata
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Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development
How the imprinted Cdkn1c locus regulates corticogenesis is unclear. Here, the authors dissect the level of cell-autonomy of imprinted Cdkn1c gene function in mouse corticogenesis and identify this as regulating radial glial progenitor cell and projection neuron survival.
- Susanne Laukoter
- , Robert Beattie
- & Simon Hippenmeyer
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Early dorsomedial tissue interactions regulate gyrification of distal neocortex
The contribution of long-range signaling to cortical gyrification remains poorly understood. In this study, authors demonstrate that the combined genetic loss of transcription factors Lmx1a and Lmx1b, expressed in the telencephalic dorsal midline neuroepithelium and head mesenchyme, respectively, induces gyrification in the mouse neocortex
- Victor V. Chizhikov
- , Igor Y. Iskusnykh
- & Kathleen J. Millen
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Quantitative single-cell live imaging links HES5 dynamics with cell-state and fate in murine neurogenesis
The single-cell gene expression changes during spinal cord formation and neurogenesis in mice are unclear. Here, the authors use a HES5 reporter to live image, then mathematically model, oscillations in single cells in presumed progenitors and neurons of the developing spinal cord.
- Cerys S. Manning
- , Veronica Biga
- & Nancy Papalopulu
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| Open Access
Yin Yang 1 sustains biosynthetic demands during brain development in a stage-specific manner
The transcription factor Yin Yang 1 (YY1) plays an important role in human disease, yet little is known about its role in brain development. This study shows that YY1 controls cerebral cortex development by maintaining proliferation and survival of neural progenitor cells via transcriptional regulation of genes involved in metabolism and protein translation.
- Luis Zurkirchen
- , Sandra Varum
- & Lukas Sommer
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| Open Access
Single-cell RNA sequencing reveals midbrain dopamine neuron diversity emerging during mouse brain development
Midbrain dopamine (mDA) neurons are significantly associated with Parkinson’s disease and yet there is no systematic molecular classification of these heterogenous group of cells. Here authors use single cell RNA sequencing of isolated mouse neurons expressing the transcription factor Pitx3 (broad mDA neuronal marker) to identify and characterize seven neuron subgroups divided in two major branches of developing Pitx3-expressing neurons.
- Katarína Tiklová
- , Åsa K. Björklund
- & Thomas Perlmann
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Transcriptome 3′end organization by PCF11 links alternative polyadenylation to formation and neuronal differentiation of neuroblastoma
In gene regulation, diversification at the transcriptome 3′end is linked to differentiation and dedifferentiation. Here, the authors discover extensive transcriptome 3′end-alterations in neuroblastoma, regulated by PCF11, and provide an interactive data repository of transcriptome-wide alternative polyadenylation.
- Anton Ogorodnikov
- , Michal Levin
- & Sven Danckwardt
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| Open Access
Elevated H3K79 homocysteinylation causes abnormal gene expression during neural development and subsequent neural tube defects
Elevated maternal homocysteine (Hcy) increases the risk for neural tube defects (NTDs) but how this arises is unclear. Here, the authors show that high levels of Hcy on histone H3K79Hcy correlate with NTDs, causing abnormal gene expression (for example Cecr2, Smarca4 and Dnmt3B) linked to neural tube closure.
- Qin Zhang
- , Baoling Bai
- & Ting Zhang
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| Open Access
KIF20A/MKLP2 regulates the division modes of neural progenitor cells during cortical development
The division of neural progenitors is closely regulated but how is unclear. Here, the authors show that mitotic kinesin KIF20A/MKLP2 interacts with a regulator of G protein signaling RGS3 in neural progenitor cells, dislodging it from the intercellular bridge of dividing cortical cells.
- Anqi Geng
- , Runxiang Qiu
- & Qiang Lu
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| Open Access
mTORC1 accelerates retinal development via the immunoproteasome
One of the determinants of the neuronal subtype produced from retinal progenitor cells is their proliferative potential. Here the authors show that mTORC1 promotes progenitor cell cycle progression and hence accelerated development in mouse retina through induction of the immunoproteasome which enhances the degradation of cyclins.
- Ji-Heon Choi
- , Hong Seok Jo
- & Jin Woo Kim
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Dlx1/2 and Otp coordinate the production of hypothalamic GHRH- and AgRP-neurons
In the hypothalamus, the arcuate nucleus (ARC) contains AgRP-neurons that regulate energy balance as well as GHRH-neurons that regulate linear growth. Here, the authors looked at how the transcription factors Dlx1/2 and Otp link development of AgRP- and GHRH-neurons.
- Bora Lee
- , Janghyun Kim
- & Jae W. Lee
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| Open Access
A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells
Unlike transcriptional regulation of hESC identity, little is known post-transcriptionally. Here, the authors show that the RNA binding protein CSDE1 regulates core components of hESC identity, neurectoderm commitment and neurogenesis to maintain pluripotency and prevent neural differentiation.
- Hyun Ju Lee
- , Deniz Bartsch
- & David Vilchez
Implication of thermal signaling in neuronal differentiation revealed by manipulation and measurement of intracellular temperature