Midbrain tectal stem cells display diverse regenerative capacities in zebrafish

Lindsey, Benjamin W.; Tang, Joel A.; Khabooshan, Mitra; Douek, Alon M.; Vandestadt, Celia; Kaslin, Jan

doi:10.1038/s41598-019-40734-z

Cited by 35 publications

(27 citation statements)

References 98 publications

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“…Wnt/β-catenin signaling is one of the most common intracellular signal transduction pathways activated in response to injury of virtually all tissues/organs ( Ozhan and Weidinger, 2014 ). While Wnt signaling has been revealed to promote regeneration of the optic tectum, the spinal cord, and the tectum of the midbrain in zebrafish ( Shimizu et al, 2012 , 2018 ; Strand et al, 2016 ; Wehner et al, 2017 ; Lindsey et al, 2019 ), it has not yet been associated with the regeneration of the telencephalon. We have used the Tg(6XTCF:dGFP) transgenic zebrafish reporter of Tcf/Lef-mediated transcription, which has been shown to sensitively detect Wnt/β-catenin pathway activity in several cellular contexts ( Shimizu et al, 2012 ).…”

Section: Resultsmentioning

confidence: 99%

Comparative Transcriptome Analysis of the Regenerating Zebrafish Telencephalon Unravels a Resource With Key Pathways During Two Early Stages and Activation of Wnt/β-Catenin Signaling at the Early Wound Healing Stage

Demırcı

Cucun

Poyraz

et al. 2020

Front. Cell Dev. Biol.

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Owing to its pronounced regenerative capacity in many tissues and organs, the zebrafish brain represents an ideal platform to understand the endogenous regeneration mechanisms that restore tissue integrity and function upon injury or disease. Although radial glial and neuronal cell populations have been characterized with respect to specific marker genes, comprehensive transcriptomic profiling of the regenerating telencephalon has not been conducted so far. Here, by processing the lesioned and unlesioned hemispheres of the telencephalon separately, we reveal the differentially expressed genes (DEGs) at the early wound healing and early proliferative stages of regeneration, i.e., 20 h post-lesion (hpl) and 3 days post-lesion (dpl), respectively. At 20 hpl, we detect a far higher number of DEGs in the lesioned hemisphere than in the unlesioned half and only 7% of all DEGs in both halves. However, this difference disappears at 3 dpl, where the lesioned and unlesioned hemispheres share 40% of all DEGs. By performing an extensive comparison of the gene expression profiles in these stages, we unravel that the lesioned hemispheres at 20 hpl and 3 dpl exhibit distinct transcriptional profiles. We further unveil a prominent activation of Wnt/β-catenin signaling at 20 hpl, returning to control level in the lesioned site at 3 dpl. Wnt/β-catenin signaling indeed appears to control a large number of genes associated primarily with the p53, apoptosis, forkhead box O (FoxO), mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) signaling pathways specifically at 20 hpl. Based on these results, we propose that the lesioned and unlesioned hemispheres react to injury dynamically during telencephalon regeneration and that the activation of Wnt/β-catenin signaling at the early wound healing stage plays a key role in the regulation of cellular and molecular events.

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Section: Resultsmentioning

confidence: 99%

Comparative Transcriptome Analysis of the Regenerating Zebrafish Telencephalon Unravels a Resource With Key Pathways During Two Early Stages and Activation of Wnt/β-Catenin Signaling at the Early Wound Healing Stage

Demırcı

Cucun

Poyraz

et al. 2020

Front. Cell Dev. Biol.

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“…Recent studies come to the contradictory answers. Ohshima’s lab showed that tectal RG were capable of producing some neurons after the stab injury (~25% of newborn cells) (Shimizu et al, 2018), whereas Kaslin’s lab reported the opposite result, in which tectal RG only produce glial cells but not neurons (Lindsey et al, 2019). Using EdU pulse-and-stain assay and Cre-loxP-based clonal analysis of tectal RG, we unambiguously demonstrate at the single-cell resolution that RG give rise to newborn glial cells (~91% of total newborn cells) with only a few neurons (~3–5% of total newborn cells) after the injury (Figure 7Q), which is mostly consistent with the study of Kaslin’s lab.…”

Section: Discussionmentioning

confidence: 99%

“…Unlike other brain regions where RG present as both dormant and proliferative forms at physiological conditions, tectal RG has been reported to be dormant, and are reactivated by injury to give rise to newborn neurons via Wnt signaling as well as Notch signaling (Shimizu et al, 2018; Ueda et al, 2018). Interestingly, a recent study showed that tectal RG produced a significant number of glial cells (~25%) but not neurons (Lindsey et al, 2019). It is essential to resolve this inconsistency on the fate potentials of injury-reactivated tectal RG.…”

Section: Introductionmentioning

confidence: 99%

Stochastic cell-cycle entry and cell-state-dependent fate outputs of injury-reactivated tectal radial glia in zebrafish

2019

eLife

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Gliosis defined as reactive changes of resident glia is the primary response of the central nervous system (CNS) to trauma. The proliferation and fate controls of injury-reactivated glia are essential but remain largely unexplored. In zebrafish optic tectum, we found that stab injury drove a subset of radial glia (RG) into the cell cycle, and surprisingly, proliferative RG responding to sequential injuries of the same site were distinct but overlapping, which was in agreement with stochastic cell-cycle entry. Single-cell RNA sequencing analysis and functional assays further revealed the involvement of Notch/Delta lateral inhibition in this stochastic cell-cycle entry. Furthermore, the long-term clonal analysis showed that proliferative RG were largely gliogenic. Notch inhibition of reactive RG, not dormant and proliferative RG, resulted in an increased production of neurons, which were short-lived. Our findings gain new insights into the proliferation and fate controls of injury-reactivated CNS glia in zebrafish.

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“…It is believed that neurogenesis in the pyramidal cell layer of the hippocampal CA1 area can promote the morphological and functional repair process after cerebral ischemia [30]. At present, it is generally believed that the enhancement of dentate gyrus neurogenesis may be a compensatory response to ischemic injury, which can promote the recovery of hippocampal function after ischemic injury [31], [32]. Studies have reported that inducing human-derived pluripotent stem cells into glial precursor cells and transplanting them into animal models of cerebral ischemia can improve the nervous system function of animals with cerebral ischemia injury [33]- [35].…”

Section: Introductionmentioning

confidence: 99%

Imaging Analysis and Evaluation of Neural Stem Cell Intracerebral Migration and Functional Reconstruction Based on Deep Learning

Zhang

Liu

2020

IEEE Access

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Neural stem cell is a type of stem cell with self-renewal ability and multi-directional differentiation potential. Under certain conditions, neural stem cells can differentiate into neurons, oligodendrocytes, and astrocytes, thereby participating in the occurrence of the nervous system. Considering that deep convolutional neural networks have better feature learning capabilities for image data than feedforward neural networks, this paper studies how to apply deep convolutional neural networks to modeling based on imaging features, and constructs convolutional neural networks. In this paper, the distribution of CD133 + neural stem cells in different neuroanatomical regions of rat brain and possible migration flow were studied. The experimental results show that there are obvious differences in the distribution of neural stem cells in different neuroanatomical regions. With the growth and development of rats, a large number of CD133 + neural stem cells migrate from the subventricular zone to the surrounding ganglia, corpus callosum, and cerebral cortex. Seven days before the operation, the rats were trained in water maze, and the EL (Escape Latency) of the rats was recorded for 1 week, 2 weeks and 1 month. Compared with the control group of sham operation, EL was significantly increased in the cerebral ischemia-reperfusion group. Compared with cerebral ischemia-reperfusion + acupuncture group and cerebral ischemia-reperfusion group, EL was significantly smaller. The results show that electroacupuncture can induce the proliferation of newborn cells in the brain and promote the differentiation of newborn cells into glial cells and nerve cells. After electroacupuncture intervention, a small number of new nerve cells already have the activity and function of secreting Ach. Electroacupuncture intervention can promote the recovery of rat nerve function after cerebral ischemia and reperfusion. INDEX TERMS Neural stem cells, migration flow, functional reconstruction, convolutional neural network.

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Midbrain tectal stem cells display diverse regenerative capacities in zebrafish

Cited by 35 publications

References 98 publications

Comparative Transcriptome Analysis of the Regenerating Zebrafish Telencephalon Unravels a Resource With Key Pathways During Two Early Stages and Activation of Wnt/β-Catenin Signaling at the Early Wound Healing Stage

Comparative Transcriptome Analysis of the Regenerating Zebrafish Telencephalon Unravels a Resource With Key Pathways During Two Early Stages and Activation of Wnt/β-Catenin Signaling at the Early Wound Healing Stage

Stochastic cell-cycle entry and cell-state-dependent fate outputs of injury-reactivated tectal radial glia in zebrafish

Imaging Analysis and Evaluation of Neural Stem Cell Intracerebral Migration and Functional Reconstruction Based on Deep Learning

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