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| Open AccessRobust elimination of genome-damaged cells safeguards against brain somatic aneuploidy following Knl1 deletion
The brain is a genomic mosaic shaped by somatic mutations and cellular responses that correct or purge these mutations. Here, by manipulating genome stability during embryonic brain development, authors revealed robust mechanisms that eliminate cells with genome damage from the brain, and the consequences of leaving somatic mutants unpurged
- Lei Shi
- , Adel Qalieh
- & Kenneth Y. Kwan
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Article
| Open AccessTET3 prevents terminal differentiation of adult NSCs by a non-catalytic action at Snrpn
The potential role of TET proteins in adult neurogenesis is unknown. In this study, authors show that TET3 is essentially required for the maintenance of the NSC pool in the adult subventricular zone niche by preventing premature differentiation of NSCs, via direct binding and repression of the paternal transcribed allele of the imprinted gene Snrpn
- Raquel Montalbán-Loro
- , Anna Lozano-Ureña
- & Sacri R. Ferrón
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| Open AccessA stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation
Induced neurons, but not induced pluripotent stem cell (iPSC)-derived neurons, preserve age-related traits. Here, the authors demonstrate that blood-derived induced neural stem cells (iNSCs), despite lacking a pluripotency transit, lose age-related signatures.
- Chao Sheng
- , Johannes Jungverdorben
- & Oliver Brüstle
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| Open AccessDirect reprogramming of fibroblasts into neural stem cells by single non-neural progenitor transcription factor Ptf1a
Fibroblasts can be reprogrammed into induced neural stem cells (iNSCs) using transcription factors expressed in neural progenitors. Here the authors show that Ptf1a, which is normally expressed in postmitotic neurons, can reprogram fibroblasts to iNSCs through Notch independent interaction with Rbpj.
- Dongchang Xiao
- , Xiaoning Liu
- & Mengqing Xiang
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Article
| Open AccessKIF20A/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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Article
| Open AccessTranscriptional synergy as an emergent property defining cell subpopulation identity enables population shift
Gaining insight into cell identities from single cell RNA-seq data remains a challenge. Here, the authors introduce an approach to identify transcription factors (TFs) that synergistically determine cellular identities, and demonstrate its ability to identify TFs that can induce cellular conversion.
- Satoshi Okawa
- , Carmen Saltó
- & Antonio del Sol
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Article
| Open AccessReducing histone acetylation rescues cognitive deficits in a mouse model of Fragile X syndrome
Loss of fragile X mental retardation protein (FMRP) leads to fragile X syndrome, associated with cognitive dysfunction. Here the authors show that mice lacking FMRP show reduced hippocampal neurogenesis and cognitive deficits, which can be rescued by reducing histone acetylation.
- Yue Li
- , Michael E. Stockton
- & Xinyu Zhao
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Article
| Open AccessIntron retention and nuclear loss of SFPQ are molecular hallmarks of ALS
Intron retention (IR) can increase protein diversity and function, and yet unregulated IR may be detrimental to cellular health. This study shows that aberrant IR occurs in ALS and finds nuclear loss of an RNA-binding protein called SFPQ as a new molecular hallmark in this devastating condition.
- Raphaelle Luisier
- , Giulia E. Tyzack
- & Rickie Patani
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Article
| Open AccessBasal condensation of Numb and Pon complex via phase transition during Drosophila neuroblast asymmetric division
Polarized localization of Numb and Pon in Drosophila neuroblasts (NBs) enables their unequal segregation during asymmetric cell divisions. Here, the authors demonstrate liquid-liquid phase separation of Pon and Numb in NBs mediated by multivalent intermolecular interactions is required for their basal condensation.
- Zelin Shan
- , Yuting Tu
- & Wenyu Wen
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Article
| Open AccessDiscordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells
Zika virus (ZIKV) infection can cause congenital Zika syndrome (CZS), but the underlying mechanisms are poorly understood. Here, the authors generate neural progenitor cells from dizygotic twins with a discordant phenotype regarding CZS and study their response to ZIKV infection.
- Luiz Carlos Caires-Júnior
- , Ernesto Goulart
- & Mayana Zatz
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Article
| Open AccessKruppel-like factor 4-dependent Staufen1-mediated mRNA decay regulates cortical neurogenesis
While being known as a transcription factor, Kruppel-like factor 4 (Klf4) may have other molecular functions. This study shows that Klf4 in neural progenitor cells regulate neurogenesis and self-renewal by interacting with RNA-binding protein Staufen1 and RNA helicase Ddx5/17 to control mRNA decay.
- Byoung-San Moon
- , Jinlun Bai
- & Wange Lu
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Article
| Open AccessInjured adult motor and sensory axons regenerate into appropriate organotypic domains of neural progenitor grafts
Understanding how transplanted cells interact with the host nervous system will be important for cell based neural regeneration approaches. Here, the authors study the sensory fate of neural progenitor cell grafts transplanted to the injured spinal cord, and show that host axons retain the ability to distinguish appropriate and inappropriate graft targets.
- Jennifer N. Dulin
- , Andrew F. Adler
- & Mark H. Tuszynski
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Article
| Open AccessNon-canonical Wnt signaling regulates neural stem cell quiescence during homeostasis and after demyelination
Following demyelination injury, neural stem cells (NSCs) in the subventricular zone switch to an activated state. Here, the authors show that a transient shift from non-canonical to canonical Wnt signaling is necessary for activation of quiescent NSCs to achieve tissue homeostasis and brain repair.
- Manideep Chavali
- , Michael Klingener
- & Adan Aguirre
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| Open AccessChromatin state changes during neural development revealed by in vivo cell-type specific profiling
While transitions between active and repressive chromatin states are essential for differentiation, little is known regarding their role during development of the brain in Drosophila. Here, the authors investigate the large scale chromatin remodelling taking place during fly neural development.
- Owen J. Marshall
- & Andrea H. Brand
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Article
| Open AccessTranscriptional signatures of schizophrenia in hiPSC-derived NPCs and neurons are concordant with post-mortem adult brains
Induced pluripotent stem cell (hiPSC)-based models have inherent variations in their cellular and molecular output and readouts. Here, Hoffman and colleagues devise a method to account for gene expression variations in hiPSC-derived neurons from patients with childhood-onset schizophrenia.
- Gabriel E. Hoffman
- , Brigham J. Hartley
- & Kristen J. Brennand
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Article
| Open AccessTen-eleven translocation 2 interacts with forkhead box O3 and regulates adult neurogenesis
Epigenetic modifications, such as DNA methylation, play an important role in adult neurogenesis. Here the authors show that Tet2, which converts 5mC to 5hmC, interacts with the transcription factor Foxo3a and regulates critical genes related to the proliferation and differentiation of adult neural stem cells.
- Xuekun Li
- , Bing Yao
- & Peng Jin
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Article
| Open AccessNeurovascular EGFL7 regulates adult neurogenesis in the subventricular zone and thereby affects olfactory perception
The vascular stem cell niche regulates the proliferation and differentiation of neural stem cells (NSCs) in the adult subventricular zone. Here the authors identify EGFL7 as a neurovascular regulator of NSCsin vivo; EGFL7-knockout mice show reduced neurogenesis, and exhibit impaired olfactory perception and behaviour.
- Frank Bicker
- , Verica Vasic
- & Mirko H. H. Schmidt
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Article
| Open AccessStage-specific functions of Semaphorin7A during adult hippocampal neurogenesis rely on distinct receptors
The functions of semaphorins in the adult brain are poorly understood. Here the authors show that Sema7A carries out stage-specific functions in the adult hippocampus via differential receptor usage; in progenitor cells, Sema7A inhibits proliferation via acting on PlexinC1, whereas in adult-born neurons, it promotes dendrite growth through β1-integrins.
- Bart C. Jongbloets
- , Suzanne Lemstra
- & R. Jeroen Pasterkamp
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| Open AccessWhole-brain 3D mapping of human neural transplant innervation
Transplantation of cells into the central nervous system has developed into a major avenue for replacing neurons lost to neurodegenerative disease. Here the authors develop an approach combining viral-based transynaptic tracing labeling and whole brain imaging to trace synaptic innervation of human neurons transplanted into a mouse background.
- Jonas Doerr
- , Martin Karl Schwarz
- & Oliver Brüstle
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| Open AccessBi- and uniciliated ependymal cells define continuous floor-plate-derived tanycytic territories
Ependymal cells lining the adult brain ventricles are comprised of multiciliated cells and a rare subpopulation with two cilia (E2 cells) whose origin and function remain unknown. Here the authors find E2 cells in the 3rd ventricle of mice and humans, along with a third ependymal cell type with only a primary cilium, and provide details of their marker profile and developmental origins.
- Zaman Mirzadeh
- , Yael Kusne
- & Arturo Alvarez-Buylla
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| Open AccessLack of Diaph3 relaxes the spindle checkpoint causing the loss of neural progenitors
Molecular mechanisms that control the division of neural progenitor cells are only partially understood. Here the authors show that Diaph3 is critical for spindle checkpoint activity in cortical progenitor cells as the loss of Diaph3 leads to apoptosis of progenitor cells and eventually results in microcephaly in mice.
- Devid Damiani
- , André M. Goffinet
- & Fadel Tissir
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Article
| Open AccessREST regulation of gene networks in adult neural stem cells
The transcription factor REST plays a crucial role in maintaining the adult neural stem cell pool. To better understand how REST maintains quiescence in neural progenitors, the authors use ChIP-seq and RNA-seq and find that REST regulates represses ribosome biogenesis, cell cycle and neuronal genes.
- Shradha Mukherjee
- , Rebecca Brulet
- & Jenny Hsieh
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| Open AccessPurification of functional human ES and iPSC-derived midbrain dopaminergic progenitors using LRTM1
Midbrain dopaminergic neurons generated from stem cells show promise for the treatment of Parkinson’s disease. Here, the authors use the cell surface marker, LRTM1, to enrich the midbrain dopaminergic progenitors and show improved motor function/cell survival when grafted into rat/monkey brains, respectively.
- Bumpei Samata
- , Daisuke Doi
- & Jun Takahashi
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Article
| Open AccessNuclear receptor NR5A2 controls neural stem cell fate decisions during development
The molecular signals regulating the decision of neural stem cells (NSC) to proliferate versus differentiate are unclear. Here, the authors identify the nuclear receptor NR5A2 as coordinating cell-cycle exit with differentiation of NSCs via direct actions on Ink4, Prox1, Notch1 and JAK/STAT.
- Athanasios Stergiopoulos
- & Panagiotis K. Politis
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| Open AccessAutophagy regulates Notch degradation and modulates stem cell development and neurogenesis
The molecular mechanisms behind how autophagy may impact on developmental pathways and cell fate decisions are unclear. Here Wu et al.identify Notch receptors being taken up into ATG16L1-positive autophagosomes and, using a mouse mutant model, show that changes in autophagy can impact on stem cell fate.
- Xiaoting Wu
- , Angeleen Fleming
- & David C. Rubinsztein
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| Open AccessTherapeutically engineered induced neural stem cells are tumour-homing and inhibit progression of glioblastoma
Neural stem cells have a tropism for glioblastoma. Here the authors employ fibroblasts directly reprogrammed into induced neural stem cells and loaded with cytotoxic molecules to migrate to xenotransplanted brain tumours in mice, achieving tumour shrinkage and prolonged survival.
- Juli R. Bagó
- , Adolfo Alfonso-Pecchio
- & Shawn D. Hingtgen
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| Open AccessThe Hippo signalling pathway maintains quiescence in Drosophila neural stem cells
Drosophila neural stem cells (NSCs) are quiescent at early larval stages but how this is regulated is unclear. Here, Ding et al. show that quiescence of NSCs is mediated by cell-contact inhibition via the Hippo pathway transmembrane proteins Crumbs and Echinoid, which in turn are regulated by nutrient levels.
- Rouven Ding
- , Kevin Weynans
- & Christian Berger
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| Open AccessPTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype
The tumor suppressor PTEN is often mutated or lost in glioblastoma. Here, the authors demonstrate that in neuronal stem cells PTEN trans-represses PAX7gene expression and PTEN deficiency promotes PAX7-dependent neoplastic transformation.
- Shunlei Duan
- , Guohong Yuan
- & Guang-Hui Liu
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Article
| Open AccessAneuploidy causes premature differentiation of neural and intestinal stem cells
It is unclear why certain tissues are more susceptible to the consequences of aneuploidy. Here, in Drosophila, Gogendeau et al.identify aneuploidy as the cause of lengthened G1 and premature differentiation in both neural and adult intestinal stem cells, which prevents cells with abnormal genomes from cycling.
- Delphine Gogendeau
- , Katarzyna Siudeja
- & Renata Basto
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| Open AccessAnalysing human neural stem cell ontogeny by consecutive isolation of Notch active neural progenitors
Profiling pluripotent stem cell (PSC)-derived neural progeny is of fundamental interest for characterizing stem cell differentiation. Here, the authors analyse neural progenitors consecutively derived from human PSCs, showing dynamic stage-specific transcriptional patterns for distinct neural progenitors.
- Reuven Edri
- , Yakey Yaffe
- & Yechiel Elkabetz
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| Open Accessα-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors
De novoneurogenesis occurs within the adult hypothalamus, suggesting the existence of a local neural stem cell niche. Here, the authors show that α-tanycytes lining the third ventricle are self-renewing multipotent neural stem cells, whose proliferation is dependent upon local FGF signalling.
- S.C. Robins
- , I. Stewart
- & M. Placzek
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Article
| Open AccessDll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis
Neural stem cells in the adult brain maintain their pool size while producing new neurons. Kawaguchi et al.show that, during neural stem cell mitosis in the adult mouse subventricular zone, the Notch ligand Dll1 is asymmetrically segregated to one daughter cell, which undergoes differentiation.
- Daichi Kawaguchi
- , Shohei Furutachi
- & Yukiko Gotoh
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Preotic neural crest cells contribute to coronary artery smooth muscle involving endothelin signalling
Endothelin-1 regulates cardiovascular development by acting on neural crest cells. Here endothelin-1-deficient mice are studied, revealing that preotic neural crest cells differentiate into coronary artery smooth muscle cells through endothelin-1-dependent mechanisms.
- Yuichiro Arima
- , Sachiko Miyagawa-Tomita
- & Hiroki Kurihara
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Direct isolation and RNA-seq reveal environment-dependent properties of engrafted neural stem/progenitor cells
Studies on neural stem and progenitor cells have shown they may be useful in treating spinal cord injuries, but the results are variable. Kumamaruet al.transplant these cells in injured spinal cords of mice, and find that their therapeutic properties are dynamically altered depending on their environment.
- Hiromi Kumamaru
- , Yasuyuki Ohkawa
- & Seiji Okada
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| Open AccessActivin induces cortical interneuron identity and differentiation in embryonic stem cell-derived telencephalic neural precursors
Signalling inputs to neural progenitors regulate the differentiation of the stem cell pool. By analysing the mechanisms occuring during neurogenesis, Cambrayet al. report that activin is the pivotal factor regulating the differentiation of telencephalic neural precursors towards a cortical interneuron fate.
- Serafí Cambray
- , Charles Arber
- & Tristan A. Rodríguez
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Homeostatic neurogenesis in the adult hippocampus does not involve amplification of Ascl1high intermediate progenitors
Neural stem cells generate neurons in the adult hippocampus, but the dynamics of neuron production remain unclear. This study shows that stem cells produce type-2a progenitors, which do not expand as previously thought, but rather generate amplifying immature neuroblasts.
- Sebastian Lugert
- , Miriam Vogt
- & Verdon Taylor
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miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells
The microRNA miR-137 is enriched in the brain of mice and induces the differentiation of adult neural stem cells. Now, Sun and colleagues report that miR-137 negatively regulates proliferation of neurons in embryonic mice and that TLX and LSD1 cooperate to negatively regulate miR-137 expression, blocking premature differentiation.
- GuoQiang Sun
- , Peng Ye
- & Yanhong Shi
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Article
| Open AccessNeural stem and progenitor cells shorten S-phase on commitment to neuron production
During neurogenesis, neural stem and progenitor cells can either proliferate or produce neurons. Here, the authors show that proliferating neural stem and progenitor cells have a longer S-phase portion of the cell cycle than cells committed to neuron production, suggesting that this may enable faithful DNA replication.
- Yoko Arai
- , Jeremy N. Pulvers
- & Wieland B. Huttner