Diversity of Adult Neural Stem and Progenitor Cells in Physiology and Disease

Finkel, Zachary; Esteban, Fatima; Rodriguez, Brianna; Fu, Tianyue; Ai, Xin; Cai, Li

doi:10.20944/preprints202106.0449.v1

Cited by 12 publications

(4 citation statements)

References 111 publications

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“…The ECM in the retina affects virtually all aspects of retina development, function and pathology (Pouw et al 2021). Retinal progenitor, neuronal, glial and vascular cells express ECM proteins and their cognate receptors enabling cell–matrix and cell–cell crosstalk (Besser et al 2012; Finkel et al 2021). In addition, the ECM shapes the structural environment in the retina and provides a niche sheltering resident cells and influencing not only neuronal and vascular cell differentiation, survival, growth, and function but also axon growth and myelination and function (Gonzalez and Brandan 2019; Rao et al 2007).…”

Section: Introductionmentioning

confidence: 99%

CCN–Hippo YAP signaling in vision and its role in neuronal, glial and vascular cell function and behavior

Chaqour

2023

J. Cell Commun. Signal.

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The retina is a highly specialized tissue composed of a network of neurons, glia, and vascular and epithelial cells; all working together to coordinate and transduce visual signals to the brain. The retinal extracellular matrix (ECM) shapes the structural environment in the retina but also supplies resident cells with proper chemical and mechanical signals to regulate cell function and behavior and maintain tissue homeostasis. As such, the ECM affects virtually all aspects of retina development, function and pathology. ECM‐derived regulatory cues influence intracellular signaling and cell function. Reversibly, changes in intracellular signaling programs result in alteration of the ECM and downstream ECM‐mediated signaling network. Our functional studies in vitro, genetic studies in mice, and multi omics analyses have provided evidence that a subset of ECM proteins referred to as cellular communication network (CCN) affects several aspects of retinal neuronal and vascular development and function. Retinal progenitor, glia and vascular cells are major sources of CCN proteins particularly CCN1 and CCN2. We found that expression of the CCN1 and CCN2 genes is dependent on the activity of YAP, the core component of the hippo‐YAP signaling pathway. Central to the Hippo pathway is a conserved cascade of inhibitory kinases that regulate the activity of YAP, the final transducer of this pathway. Reversibly, YAP expression and/or activity is dependent on CCN1 and CCN2 downstream signaling, which creates a positive or negative feedforward loop driving developmental processes (e.g., neurogenesis, gliogenesis, angiogenesis, barriergenesis) and, when dysregulated, disease progression in a range of retinal neurovascular disorders. Here we describe mechanistic hints involving the CCN–Hippo–YAP regulatory axis in retina development and function. This regulatory pathway represents an opportunity for targeted therapies in neurovascular and neurodegenerative diseases.

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Section: Introductionmentioning

confidence: 99%

CCN–Hippo YAP signaling in vision and its role in neuronal, glial and vascular cell function and behavior

Chaqour

2023

J. Cell Commun. Signal.

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“…Particularly, the hypothalamic region has been extensively studied in regard to neurogenesis/gliogenesis and development 13 . A variety of proliferating cell types has been identified in this region, including glial-like cells, neuronal progenitors, astrocyte progenitors, and oligodendrocyte progenitors [14][15][16] . More recently, scRNA-seq data analysis of 207,785 cells of adult macaque hippocampus revealed a comprehensive single-cell transcriptome atlas of neurogenesis for primates 10 .…”

Section: Introductionmentioning

confidence: 99%

An integrated single-cell transcriptome landscape of postnatal mouse hypothalamus

Junaid

Choe

Kondoh

et al. 2023

Preprint

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SummaryThe neural stem cells (NSCs) in the hypothalamus are relatively more narrowly defined than in other neurogenic regions of the postnatal brain. By leveraging single-cell RNA sequencing (scRNA-seq) data, we generated an integrated reference dataset comprising 296,282 cells from postnatal hypothalamic regions and the adjacent region, bed nucleus of the stria terminalis (BNST), and identified 30 hypothalamic neuronal and non-neuronal cell populations. The analyses of their gene expression pattern, and specific differentiation trajectories reveal the presence of NSCs and intermediate progenitor cells (IPCs) that show a continuum of activation and differentiation processes in the hypothalamus after birth. Through comparative analyses of the integrated dataset with our lab-generated Connect-seq data obtained from the whole hypothalamus, we further assessed the technical validity of the dataset presented in this study. Our large-scale unified scRNA-seq dataset with harmonized cell-level metadata can serve as a valuable resource for investigating cell type-specific gene expression and cellular differentiation trajectories in the postnatal mouse hypothalamus.

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“…It is known that the Sonic hedgehog (SHH) signaling pathway activator, Hh-Ag 1.5, is a potent mitogen in the developing spinal cord [17], and WNT, SHH and BMP signaling pathways define the dorsal-ventral axis of the developing spinal cord. Furthermore, NSCs are able to differentiate into Tuj1-positive neurons, glial fibrillary acidic protein (GFAP)-positive astrocytes and myelin basic protein (MBP)-positive oligodendrocytes, which may play potential roles in regenerative medicine [18].…”

Section: Introductionmentioning

confidence: 99%

In-vitro differentiation of human embryonic stem cells into spinal cord neural stem cells

Chen

Zhao

et al. 2022

NeuroReport

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In-vitro differentiation of human embryonic stem cells into spinal cord neural stem cells (NSCs) can help researchers better understand the cellular processes associated with spinal cord development and regeneration, and provide therapeutic strategies for spinal cord disorders. However, effective and consistent methods for the generation of human spinal cord NSCs are rare. Objective of the study is to establish methods for the in-vitro induction and long-term maintenance of human spinal cord NSCs. H9 cells were treated with neural induction medium for 10 days under single-cell seeding condition, followed by treatment with neural maintenance medium and replacement with NSC medium after five passages. The identity of the generated cells was determined by immunofluorescence, immunoblotting, and cleavage under targets and tagmentation (CUT&Tag) assays. After the neural induction, OCT4, an embryonic stem cell marker, was significantly reduced, whereas NESTIN and PAX6, two NSC markers, were clearly increased. After the neural maintenance, most of the H9-derived cells consistently expressed NESTIN and PAX6 together with SOX1 and HOXC9, two spinal cord markers. The Homer known motif enrichment results of the CUT&Tag assay confirmed the expression of HOXC9 in the H9-derived spinal cord NSCs, which can be maintained for more than 40 days under an in vitro culture system. This study sheds new light on effective induction and maintenance of human spinal cord NSCs.

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Diversity of Adult Neural Stem and Progenitor Cells in Physiology and Disease

Cited by 12 publications

References 111 publications

CCN–Hippo YAP signaling in vision and its role in neuronal, glial and vascular cell function and behavior

CCN–Hippo YAP signaling in vision and its role in neuronal, glial and vascular cell function and behavior

An integrated single-cell transcriptome landscape of postnatal mouse hypothalamus

In-vitro differentiation of human embryonic stem cells into spinal cord neural stem cells

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