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Article
| Open Access
Intron detention tightly regulates the stemness/differentiation switch in the adult neurogenic niche
mRNAs associated with differentiated cells are already detected in adult neural stem cells. Here the authors show how intron detention prevents their translation, solving conflicts in fate decisions while priming stem cells for timely differentiation.
- Ainara González-Iglesias
- , Aida Arcas
- & M. Angela Nieto
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Article
| Open Access
Autophagy drives the conversion of developmental neural stem cells to the adult quiescent state
Neural stem cells in the adult mammalian brain derive from proliferating precursors that are spared as dormant reservoirs during development. Here, the authors show that autophagy is required for neural stem cells to transition to the adult quiescent state.
- Isabel Calatayud-Baselga
- , Lucía Casares-Crespo
- & Helena Mira
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Article
| Open Access
Emergence of task-related spatiotemporal population dynamics in transplanted neurons
Cell therapy is a promising treatment for brain injury, but it is unclear if transplanted neurons demonstrate population dynamics. By monitoring transplanted neurons in injured mice, here the authors show the emergence of dynamics resembling intact networks.
- Harman Ghuman
- , Kyungsoo Kim
- & Karunesh Ganguly
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Article
| Open Access
Subventricular zone cytogenesis provides trophic support for neural repair in a mouse model of stroke
The functions of newborn cells arising from the subventricular zone in response to stroke have been unclear. Here, the authors show that cells migrating from the subventricular zone after stroke promote brain repair and functional recovery in mice.
- Michael R. Williamson
- , Stephanie P. Le
- & Michael R. Drew
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Article
| Open Access
Human forebrain organoid-based multi-omics analyses of PCCB as a schizophrenia associated gene linked to GABAergic pathways
Identifying schizophrenia risk genes is essential for illuminating the disease etiology. Here, authors prioritized Propionyl-CoA Carboxylase Subunit Beta (PCCB) as a schizophrenia-associated gene, and linked PCCB to GABAergic pathways using human forebrain organoids-based transcriptomic and metabolomic analysis.
- Wendiao Zhang
- , Ming Zhang
- & Qingtuan Meng
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Article
| Open Access
Platelet-derived exerkine CXCL4/platelet factor 4 rejuvenates hippocampal neurogenesis and restores cognitive function in aged mice
Exercise has positive effects on the brain during aging. Here the authors show that in mice, platelet-released exerkine PF4 mediates the effects of exercise on the brain.
- Odette Leiter
- , David Brici
- & Tara L. Walker
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Article
| Open Access
Neural precursor cells tune striatal connectivity through the release of IGFBPL1
The physiological role of endogenous neural protenitor cells of the subventricular zone in adult stage is not fully understood. Here the authors show that in mice, these cells tune neuronal activity of the striatum via insulin-like growth factor binding protein-like 1 and cognitive functions.
- Erica Butti
- , Stefano Cattaneo
- & Gianvito Martino
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Article
| Open Access
Characterization of an RNA binding protein interactome reveals a context-specific post-transcriptional landscape of MYC-amplified medulloblastoma
MYC amplification is an independent prognostic factor for the most aggressive subgroup (Group 3) of pediatric medulloblastoma (G3 MB). Here, the authors highlight the role of the RNA-binding protein, Musashi-1 (MSI1) in G3 MB and identify MSI1-bound targets sharing MYC associated pathways.
- Michelle M. Kameda-Smith
- , Helen Zhu
- & Sheila K. Singh
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Article
| Open Access
Signal requirement for cortical potential of transplantable human neuroepithelial stem cells
The regulatory pathways that control the human neural progenitor cell pool are not well understood. Here, Varga et al. identify signals that control the division of human pluripotent stem cell derived neural stem cells and their ability to make cortical neurons and glia.
- Balazs V. Varga
- , Maryam Faiz
- & Andras Nagy
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Article
| Open Access
16p11.2 deletion is associated with hyperactivation of human iPSC-derived dopaminergic neuron networks and is rescued by RHOA inhibition in vitro
16p11.2 CNVs are associated with neurodevelopmental disorders. Here, the authors show that 16p11.2 deletion is associated with hyperactivation of human iPSC-derived dopaminergic neuron networks and is rescued by RHOA inhibition in vitro.
- Maria Sundberg
- , Hannah Pinson
- & Mustafa Sahin
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Article
| Open Access
Deep learning-based predictive identification of neural stem cell differentiation
The differentiation of neural stem cells (NSCs) into neurons is a critical part in devising potential cell-based therapeutic strategies for central nervous system diseases but NSCs fate determination and prediction is problematic. Here, the authors present a deep neural network model for predictable reliable identification of NSCs fate.
- Yanjing Zhu
- , Ruiqi Huang
- & Rongrong Zhu
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Article
| Open Access
A critical period of neuronal activity results in aberrant neurogenesis rewiring hippocampal circuitry in a mouse model of epilepsy
Adult-born granule cells integrate in hippocampal circuitry and contribute to hippocampal function. Here, the authors show that a critical period of neuronal activity regulates aberrant neurogenesis to rewire hippocampal circuitry and drive seizures in a mouse model of epilepsy.
- Zane R. Lybrand
- , Sonal Goswami
- & Jenny Hsieh
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Article
| Open Access
Long-term exposure to a hypomagnetic field attenuates adult hippocampal neurogenesis and cognition
Exposure to a hypomagnetic field (HMF) influences the cognitive processes of various animals, from insects to human beings. The authors show that in mice exposed to HMF, adult hippocampal neurogenesis and hippocampusdependent learning are impaired and could be rescued by restoring ROS levels.
- Bingfang Zhang
- , Lei Wang
- & Yongxin Pan
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Review Article
| Open Access
Steps towards standardized quantification of adult neurogenesis
Adult neurogenesis is involved in several physiological and pathological processes, however standardization for the quantification of new born neurons is lacking. Here, the authors provide guidance to improve reproducibility and rigour in cell quantification.
- Xinyu Zhao
- & Henriette van Praag
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Article
| Open Access
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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Article
| Open Access
Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs
Here, authors present results of a hiPSC transcriptomics study on corticogenesis from multiple donors across four transitions in differentiation. They present a bulk data deconvolution method and show that co-culturing human NPCs with rodent astrocytes results in mutually synergistic maturation.
- Emily E. Burke
- , Joshua G. Chenoweth
- & Andrew E. Jaffe
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Article
| Open Access
Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life
Ageing affects several brain areas causing a decrease in cognitive abilities and memory. We find that increasing the endogenous potential of the hippocampus to generate new neurons throughout life rejuvenates learning and memory, indicating that neural reserves can be exploited during ageing to compensate for age- or disease-related cognitive impairments.
- Gabriel Berdugo-Vega
- , Gonzalo Arias-Gil
- & Federico Calegari
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Article
| Open Access
Enhanced lysosomal degradation maintains the quiescent state of neural stem cells
It remains unclear why quiescent neural stem cells (qNSCs) in the subventricular zone of the mouse brain have enlarged lysosomes. Here, authors demonstrate that qNSCs exhibit higher lysosomal activity and degrade activated EGF receptor by endolysosomal degradation more rapidly than proliferating NSCs, which prevents the NSC exit from quiescence.
- Taeko Kobayashi
- , Wenhui Piao
- & Ryoichiro Kageyama
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Article
| Open Access
Robust 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 Access
HSP90-incorporating chaperome networks as biosensor for disease-related pathways in patient-specific midbrain dopamine neurons
The early molecular events that ultimately lead to neuronal cell death in pathologies such as Parkinson’s disease are poorly understood. Here the authors use pluripotent stem-cell-derived human midbrain neurons and chemical biology tools to gain molecular level insight into the events induced by toxic and genetic stresses that mimic those occurring during neurodegeneration.
- Sarah Kishinevsky
- , Tai Wang
- & Lorenz Studer
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Article
| Open Access
Human neuroepithelial stem cell regional specificity enables spinal cord repair through a relay circuit
The optimal type or regional origin of stem cells for regenerative applications in the nervous system has not yet been established. Here the authors show that human neuroepithelial stem cells from the developing spinal cord, but not those from the developing cortex, show good host-graft interaction when transplanted to rodent models of spinal cord injury.
- Maria Teresa Dell’Anno
- , Xingxing Wang
- & Stephen M. Strittmatter
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Article
| Open Access
Direct 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 Access
Reducing 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 Access
Injured 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 Access
Transcriptional 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 Access
Stage-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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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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Article
| Open Access
Activin 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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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 Access
Neural 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
Reconstruction of macroglia and adult neurogenesis evolution through cross-species single-cell transcriptomic analyses