scholarly journals High resolution mouse subventricular zone stem cell niche transcriptome reveals features of lineage, anatomy, and aging

2020 ◽  
Author(s):  
Xuanhua P. Xie ◽  
Dan R. Laks ◽  
Daochun Sun ◽  
Asaf Poran ◽  
Ashley M. Laughney ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Single Cell ◽  
Rna Sequencing ◽  
Subventricular Zone ◽  
Stem Cell Niche ◽  
Advanced Age ◽  
Single Cell Rna Sequencing ◽  
Cell Niche

AbstractAdult neural stem cells (NSC) serve as a reservoir for brain plasticity and origin for certain gliomas. Lineage tracing and genomic approaches have portrayed complex underlying heterogeneity within the major anatomical location for NSC, the subventricular zone (SVZ). To gain a comprehensive profile of NSC heterogeneity, we utilized a well validated stem/progenitor specific reporter transgene in concert with single cell RNA sequencing to achieve unbiased analysis of SVZ cells from infancy to advanced age. The magnitude and high specificity of the resulting transcriptional data sets allow precise identification of the varied cell types embedded in the SVZ including specialized parenchymal cells (neurons, glia, microglia), and non-central nervous system cells (endothelial, immune). Initial mining of the data delineates four quiescent NSC and three progenitor cell subpopulations formed in a linear progression. Further evidence indicates that distinct stem and progenitor populations reside in different regions of the SVZ. As stem/progenitor populations progress from neonatal to advanced age, they acquire a deficiency in transition from quiescence to proliferation. Further data mining identifies stage specific biological processes, transcription factor networks, and cell surface markers for investigation of cellular identities, lineage relationships, and key regulatory pathways in adult NSC maintenance and neurogenesis.Significance StatementAdult neural stem cells (NSC) are closely related to multiple neurological disorders and brain tumors. Comprehensive investigation of their composition, lineage, and aging will provide new insights that may lead to enhanced patient treatment. This study applies a novel transgene to label and manipulate neural stem/progenitor cells, and monitor their evolution during aging. Together with high-throughput single cell RNA sequencing, we are able to analyze the subventricular zone (SVZ) cells from infancy to advanced age with unprecedented granularity. Diverse new cell states are identified in the stem cell niche, and an aging related NSC deficiency in transition from quiescence to proliferation is identified. The related biological features provide rich resources to inspect adult NSC maintenance and neurogenesis.

scholarly journals Fractone bulbs derive from ependymal cells and their laminin composition influence the stem cell niche in the subventricular zone

2016 ◽  
Author(s):  
Marcos Assis Nascimento ◽  
Lydia Sorokin ◽  
Tatiana Coelho-Sampaio
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Adult Neurogenesis ◽  
Subventricular Zone ◽  
Stem Cell Niche ◽  
Ependymal Cells ◽  
Cell Niche

AbstractFractones are extracellular matrix structures in the neural stem cell niche of the subventricular zone (SVZ), where they appear as round deposits named bulbs or thin branching lines called stems. Their cellular origin and what determines their localization at this site is poorly studied and it remains unclear whether they influence neural stem and progenitor cells formation, proliferation and/or maintenance. To address these questions, we analyzed whole mount preparations of the lateral ventricle by confocal microscopy using different extracellular matrix and cell markers. We found that bulbs are rarely connected to stems and that they contain laminin α5 and α2 chains, respectively. Fractone bulbs were profusely distributed throughout the SVZ and appeared associated with the center of pinwheels, a critical site for adult neurogenesis. We demonstrate that bulbs appear at the apical membrane of ependymal cells at the end of the first week after birth. The use of transgenic mice lacking laminin α5 gene expression (Lama5) in endothelium and in FoxJ1-expressing ependymal cells, revealed ependymal cells as the source of laminin α5-containing fractone bulbs. Loss of laminin α5 from bulbs correlated with a 60% increase in cell proliferation, as determined by PH3 staining, and with a selective reduction in the number of quiescent neural stem cells in the SVZ. These results indicate that fractones are a key component of the SVZ and suggest that laminin α5 modulates the physiology of the neural stem cell niche.Significance StatementOur work unveils key aspects of fractones, extracellular matrix structures present in the SVZ that still lack a comprehensive characterization. We show that fractones extensively interact with neural stem cells, whereas some of them are located precisely at pinwheel centers, which are hotspots for adult neurogenesis. Our results also demonstrate that fractones increase in size during aging and that their interactions with NSPCs become more complex in old mice. Lastly, we show that fractone bulbs are produced by ependymal cells and that their laminin content regulates neural stem cells.

Estrogen Selectively Mobilizes Neural Stem Cells in the Third Ventricle Stem Cell Niche of Postnatal Day 21 Rats

2015 ◽  
Vol 52 (2) ◽  
pp. 927-933 ◽  
Author(s):  
Zhen He ◽  
Li Cui ◽  
Merle G. Paule ◽  
Sherry A. Ferguson
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Stem Cell Niche ◽  
Third Ventricle ◽  
The Third ◽  
Cell Niche

STEM-27. A PERIVASCULAR STEM CELL UNDERLIES VERTEBRATE MENINGEAL TUMORIGENESIS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi26-vi27
Author(s):  
Abrar Choudhury ◽  
Martha Cady ◽  
Calixto Lucas ◽  
Brisa Palikuqi ◽  
Ophir Klein ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Single Cell ◽  
Tumor Cells ◽  
Rna Sequencing ◽  
Single Cells ◽  
Cell Types ◽  
Human Meningioma ◽  
Single Cell Rna Sequencing ◽  
Human Meningiomas

Abstract BACKGROUND Meningiomas are the most common primary intracranial tumors in humans and dogs, but biologic drivers and cell types underlying meningeal tumorigenesis are incompletely understood. Here we integrate meningioma single-cell RNA sequencing with stem cell approaches to define a perivascular stem cell underlying vertebrate meningeal tumorigenesis. METHODS Single-cell RNA sequencing was performed on 57,114 cells from 8 human meningiomas, 54,607 cells from 3 dog meningiomas, and human meningioma xenografts in mice. Results were validated using immunofluorescence (IF), immunohistochemistry (IHC), and deconvolution of bulk RNA sequencing of 200 human meningiomas. Mechanistic and functional studies were performed using clonogenic and limiting dilution assays, xenografts, and genetically engineered mouse models. RESULTS Copy number variant identification from human meningioma single cells distinguished tumor cells with loss of chr22q from non-tumor cells with intact chr22q. A single cluster distinguished by expression of Notch3 and other cancer stem cell genes had an intermediate level of loss of chr22q, suggesting this cluster may represent meningioma stem cells. In support of this hypothesis, pseudotime trajectory analysis demonstrated transcriptomic progression starting from Notch3+ cells and encompassing all other meningioma cell types. Notch3+ meningioma cells had transcriptomic concordance to mural pericytes, and IF/IHC of prenatal and adult human meninges, as well as lineage tracing using a Notch3-CreERT2 allele in mice, confirmed Notch3+ cells were restricted to the perivascular stem cell niche in mammalian meningeal development and homeostasis. Integrating human and dog meningioma single cells revealed Notch3+ cells in tumor and non-tumor clusters in dog meningiomas. Notch3 IF/IHC and cell-type deconvolution of bulk RNA sequencing showed Notch3+ cells were enriched in high-grade human meningiomas. Notch3 overexpression in human meningioma cells increased clonogenic growth in vitro, and increased tumorigenesis and tumor growth in vivo, decreasing overall survival. CONCLUSIONS Notch3+ stem cells in the perivascular niche underlie vertebrate meningeal tumorigenesis.

scholarly journals Histological Studies of the Ventricular–Subventricular Zone as Neural Stem Cell and Glioma Stem Cell Niche

2021 ◽  
pp. 002215542110320
Author(s):  
Asa A. Brockman ◽  
Bret C. Mobley ◽  
Rebecca A. Ihrie
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tumor Cells ◽  
Neural Stem Cell ◽  
Subventricular Zone ◽  
Stem Cell Niche ◽  
Special Focus ◽  
Neural Stem Cell Niche ◽  
Stem And Progenitor Cells ◽  
Cell Niche

The neural stem cell niche of the ventricular–subventricular zone supports the persistence of stem and progenitor cells in the mature brain. This niche has many notable cytoarchitectural features that affect the activity of stem cells and may also support the survival and growth of invading tumor cells. Histochemical studies of the niche have revealed many proteins that, in combination, can help to reveal stem-like cells in the normal or cancer context, although many caveats persist in the quest to consistently identify these cells in the human brain. Here, we explore the complex relationship between the persistent proliferative capacity of the neural stem cell niche and the malignant proliferation of brain tumors, with a special focus on histochemical identification of stem cells and stem-like tumor cells and an eye toward the potential application of high-dimensional imaging approaches to the field.

scholarly journals A cell atlas of the adult Drosophila midgut

2020 ◽  
Vol 117 (3) ◽  
pp. 1514-1523 ◽  
Author(s):  
Ruei-Jiun Hung ◽  
Yanhui Hu ◽  
Rory Kirchner ◽  
Yifang Liu ◽  
Chiwei Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Single Cell ◽  
Rna Sequencing ◽  
Cell Biology ◽  
Single Cells ◽  
Intestinal Stem Cells ◽  
Cell Type ◽  
Molecular Features ◽  
Single Cell Rna Sequencing

Studies of the adult Drosophila midgut have led to many insights in our understanding of cell-type diversity, stem cell regeneration, tissue homeostasis, and cell fate decision. Advances in single-cell RNA sequencing provide opportunities to identify new cell types and molecular features. We used single-cell RNA sequencing to characterize the transcriptome of midgut epithelial cells and identified 22 distinct clusters representing intestinal stem cells, enteroblasts, enteroendocrine cells (EEs), and enterocytes. This unbiased approach recovered most of the known intestinal stem cells/enteroblast and EE markers, highlighting the high quality of the dataset, and led to insights on intestinal stem cell biology, cell type-specific organelle features, the roles of new transcription factors in progenitors and regional variation along the gut, 5 additional EE gut hormones, EE hormonal expression diversity, and paracrine function of EEs. To facilitate mining of this rich dataset, we provide a web-based resource for visualization of gene expression in single cells. Altogether, our study provides a comprehensive resource for addressing functions of genes in the midgut epithelium.

scholarly journals A comprehensive temporal patterning gene network in Drosophila medulla neuroblasts revealed by single-cell RNA sequencing

2021 ◽  
Author(s):  
Hailun Zhu ◽  
Sihai Dave Zhao ◽  
Alokananda Ray ◽  
Yu Zhang ◽  
Xin Li
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Transcription Factors ◽  
Neural Stem Cells ◽  
Single Cell ◽  
Rna Sequencing ◽  
Gene Network ◽  
Temporal Patterning ◽  
Single Cell Rna Sequencing ◽  
High Gradients

During development, neural stem cells are temporally patterned to sequentially generate a variety of neural types before exiting the cell cycle. Temporal patterning is well-studied in Drosophila, where neural stem cells called neuroblasts sequentially express cascades of Temporal Transcription Factors (TTFs) to control the birth-order dependent neural specification. However, currently known TTFs were mostly identified through candidate approaches and may not be complete. In addition, many fundamental questions remain concerning the TTF cascade initiation, progression, and termination. It is also not known why temporal progression only happens in neuroblasts but not in their differentiated progeny. In this work, we performed single-cell RNA sequencing of Drosophila medulla neuroblasts of all ages to study the temporal patterning process with single-cell resolution. Our scRNA-seq data revealed that sets of genes involved in different biological processes show high to low or low to high gradients as neuroblasts age. We also identified a list of novel TTFs, and experimentally characterized their roles in the temporal progression and neural fate specification. Our study revealed a comprehensive temporal gene network that patterns medulla neuroblasts from start to end. Furthermore, we found that the progression and termination of this temporal cascade also require transcription factors differentially expressed along the differentiation axis (neuroblasts -> -> neurons). Lola proteins function as a speed modulator of temporal progression in neuroblasts; while Nerfin-1, a factor required to suppress de-differentiation in post-mitotic neurons, acts at the final temporal stage together with the last TTF of the cascade, to promote the switch to gliogenesis and the cell cycle exit. Our comprehensive study of the medulla neuroblast temporal cascade illustrated mechanisms that might be conserved in the temporal patterning of neural stem cells.

scholarly journals Systemic and local cues drive neural stem cell niche remodelling during neurogenesis in Drosophila

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Pauline Spéder ◽  
Andrea H Brand
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neuronal Differentiation ◽  
Neural Stem Cell ◽  
Stem Cell Niche ◽  
Environmental Changes ◽  
Newborn Neuron ◽  
Membrane Processes ◽  
Cell Niche

Successful neurogenesis requires adequate proliferation of neural stem cells (NSCs) and their progeny, followed by neuronal differentiation, maturation and survival. NSCs inhabit a complex cellular microenvironment, the niche, which influences their behaviour. To ensure sustained neurogenesis, niche cells must respond to extrinsic, environmental changes whilst fulfilling the intrinsic requirements of the neurogenic program and adapting their roles accordingly. However, very little is known about how different niche cells adjust their properties to such inputs. Here, we show that nutritional and NSC-derived signals induce the remodelling of Drosophila cortex glia, adapting this glial niche to the evolving needs of NSCs. First, nutrition-induced activation of PI3K/Akt drives the cortex glia to expand their membrane processes. Second, when NSCs emerge from quiescence to resume proliferation, they signal to glia to promote membrane remodelling and the formation of a bespoke structure around each NSC lineage. The remodelled glial niche is essential for newborn neuron survival.

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