scholarly journals Structurally Distinct LewisX Glycans Distinguish Subpopulations of Neural Stem/Progenitor Cells

2011 ◽  
Vol 286 (18) ◽  
pp. 16321-16331 ◽  
Author(s):  
Eva Hennen ◽  
Tim Czopka ◽  
Andreas Faissner
Keyword(s):  
Progenitor Cells ◽  
Carbohydrate Binding ◽  
Neural Cells ◽  
Stem Cell Markers ◽  
Binding Assays ◽  
Embryonic Mouse ◽  
Isolation And Characterization ◽  
Neural Stem Progenitor Cells

There is increasing evidence that the stem and progenitor cell population that builds the central nervous system is very heterogeneous. Stem cell markers with the potential to divide this cell pool into subpopulations with distinct characteristics are sparse. We were looking for new cell type-specific antigens to further subdivide the progenitor pool. Here, we introduce the novel monoclonal antibody clone 5750. We show that it specifically labels cell surfaces of neural stem and progenitor cells. When 5750-expressing cells were isolated by fluorescence-activated cell sorting from embryonic mouse brains, the sorted population showed increased neurosphere forming capacity and multipotency. Neurospheres generated from 5750-positive cells could self-renew and remained multipotent even after prolonged passaging. Carbohydrate binding assays revealed that the 5750 antibody specifically binds to LewisX-related carbohydrates. Interestingly, we found that the LewisX epitope recognized by clone 5750 differs from those detected by other anti-LewisX antibody clones like 487LeX, SSEA-1LeX, and MMALeX. Our data further reveal that individual anti-LewisX clones can be successfully used to label and deplete different subpopulations of neural cells in vivo and in vitro. In conclusion, we present a new tool for the isolation and characterization of neural subpopulations and provide insights into the complexity of cell surface glycosylation.

scholarly journals Precocious neuronal differentiation and disrupted oxygen responses in Kabuki syndrome

2018 ◽  
Author(s):  
Giovanni A. Carosso ◽  
Leandros Boukas ◽  
Jonathan J. Augustin ◽  
Ha Nam Nguyen ◽  
Briana L. Winer ◽  
...  
Keyword(s):  
Neuronal Differentiation ◽  
Transcriptional Activation ◽  
Brain Cell ◽  
Model Systems ◽  
Neural Cells ◽  
Kabuki Syndrome ◽  
Neural Stem Progenitor Cells ◽  
Chromatin Profiling

AbstractChromatin modifiers act to coordinate gene expression changes critical to neuronal differentiation from neural stem/progenitor cells (NSPCs). Lysine-specific methyltransferase 2D (KMT2D) encodes a histone methyltransferase that promotes transcriptional activation, and is frequently mutated in cancers and in the majority (>70%) of patients diagnosed with the congenital, multisystem intellectual disability (ID) disorder Kabuki syndrome 1 (KS1). Critical roles for KMT2D are established in various non-neural tissues, but the effects of KMT2D loss in brain cell development have not been described. We conducted parallel studies of proliferation, differentiation, transcription, and chromatin profiling in KMT2D-deficient human and mouse models to define KMT2D-regulated functions in neurodevelopmental contexts, including adult-born hippocampal NSPCs in vivo and in vitro. We report cell-autonomous defects in proliferation, cell cycle, and survival, accompanied by early NSPC maturation in several KMT2D-deficient model systems. Transcriptional suppression in KMT2D-deficient cells indicated strong perturbation of hypoxia-responsive metabolism pathways. Functional experiments confirmed abnormalities of cellular hypoxia responses in KMT2D-deficient neural cells, and accelerated NSPC maturation in vivo. Together, our findings support a model in which loss of KMT2D function suppresses expression of oxygen-responsive gene programs important to neural progenitor maintenance, resulting in precocious neuronal differentiation in a mouse model of KS1.Graphical Abstract

scholarly journals Conditional Activation of Bmi1 Expression Regulates Self-renewal, Apoptosis, and Differentiation of Neural Stem/Progenitor Cells In Vitro and In Vivo

Stem Cells ◽  
2011 ◽  
Vol 29 (4) ◽  
pp. 700-712 ◽  
Author(s):  
Gokhan Yadirgi ◽  
Veronica Leinster ◽  
Serena Acquati ◽  
Heeta Bhagat ◽  
Olga Shakhova ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Self Renewal ◽  
Bmi1 Expression ◽  
Neural Stem Progenitor Cells

scholarly journals Visualization of individual cell division history in complex tissues

2020 ◽  
Author(s):  
Annina Denoth-Lippuner ◽  
Baptiste N. Jaeger ◽  
Tong Liang ◽  
Stefanie E. Chie ◽  
Lars N. Royall ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Progenitor Cells ◽  
Individual Cell ◽  
Cell Divisions ◽  
Mouse Tissues ◽  
Single Cell Rna Sequencing ◽  
Neural Stem Progenitor Cells

SummaryThe division potential of individual stem cells and the molecular consequences of successive rounds of proliferation remain largely unknown. We developed an inducible cell division counter (iCOUNT) that reports cell division events in human and mouse tissues in vitro and in vivo. Analysing cell division histories of neural stem/progenitor cells (NSPCs) in the developing and adult brain, we show that iCOUNT allows for novel insights into stem cell behaviour. Further, we used single cell RNA-sequencing (scRNA-seq) of iCOUNT-labelled NSPCs and their progenies from the developing mouse cortex and forebrain-regionalized human organoids to identify molecular pathways that are commonly regulated between mouse and human cells, depending on individual cell division histories. Thus, we developed a novel tool to characterize the molecular consequences of repeated cell divisions of stem cells that allows an analysis of the cellular principles underlying tissue formation, homeostasis, and repair.HighlightsiCOUNT reports previous cell divisions in mouse and human cells in vitroiCOUNT detects cell division biographies in complex mouse tissues in vivoiCOUNT allows for the analysis of human neural stem/progenitor cells in human forebrain organoidsSingle cell RNA-sequencing of iCOUNT cells derived from the mouse developing cortex and human forebrain organoids identifies molecular consequences of previous rounds of cell divisionsGraphical abstract

scholarly journals Characterization of Human Hippocampal Neural Stem/Progenitor Cells and Their Application to Physiologically Relevant Assays for Multiple Ionotropic Glutamate Receptors

2014 ◽  
Vol 19 (8) ◽  
pp. 1174-1184 ◽  
Author(s):  
Kazuyuki Fukushima ◽  
Yoshikuni Tabata ◽  
Yoichi Imaizumi ◽  
Naohiro Kohmura ◽  
Michiko Sugawara ◽  
...  
Keyword(s):  
Glutamate Receptors ◽  
Progenitor Cells ◽  
Brain Region ◽  
Long Term Potentiation ◽  
Ionotropic Glutamate Receptors ◽  
Neural Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Neural Stem Progenitor Cells

The hippocampus is an important brain region that is involved in neurological disorders such as Alzheimer disease, schizophrenia, and epilepsy. Ionotropic glutamate receptors—namely, N-methyl-D-aspartate (NMDA) receptors (NMDARs), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors (AMPARs), and kainic acid (KA) receptors (KARs)—are well known to be involved in these diseases by mediating long-term potentiation, excitotoxicity, or both. To predict the therapeutic efficacy and neuronal toxicity of drug candidates acting on these receptors, physiologically relevant systems for assaying brain region–specific human neural cells are necessary. Here, we characterized the functional differentiation of human fetal hippocampus–derived neural stem/progenitor cells—namely, HIP-009 cells. Calcium rise assay demonstrated that, after a 4-week differentiation, the cells responded to NMDA (EC50 = 7.5 ± 0.4 µM; n = 4), AMPA (EC50 = 2.5 ± 0.1 µM; n = 3), or KA (EC50 = 33.5 ± 1.1 µM; n = 3) in a concentration-dependent manner. An AMPA-evoked calcium rise was observed in the absence of the desensitization inhibitor cyclothiazide. In addition, the calcium rise induced by these agonists was inhibited by antagonists for each receptor—namely, MK-801 for NMDA stimulation (IC50 = 0.6 ± 0.1 µM; n = 4) and NBQX for AMPA and KA stimulation (IC50 = 0.7 ± 0.1 and 0.7 ± 0.03 µM, respectively; n = 3). The gene expression profile of differentiated HIP-009 cells was distinct from that of undifferentiated cells and closely resembled that of the human adult hippocampus. Our results show that HIP-009 cells are a unique tool for obtaining human hippocampal neural cells and are applicable to systems for assay of ionotropic glutamate receptors as a physiologically relevant in vitro model.

scholarly journals Soluble JAM-C Ectodomain Serves as the Niche for Adipose-Derived Stromal/Stem Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 278
Author(s):  
Morio Yamazaki ◽  
Kotaro Sugimoto ◽  
Yo Mabuchi ◽  
Rina Yamashita ◽  
Naoki Ichikawa-Tomikawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Adhesion ◽  
Progenitor Cells ◽  
Soluble Form ◽  
Interstitial Tissue ◽  
Stem Cell Markers ◽  
Stem And Progenitor Cells ◽  
Stromal Stem Cells

Junctional adhesion molecules (JAMs) are expressed in diverse types of stem and progenitor cells, but their physiological significance has yet to be established. Here, we report that JAMs exhibit a novel mode of interaction and biological activity in adipose-derived stromal/stem cells (ADSCs). Among the JAM family members, JAM-B and JAM-C were concentrated along the cell membranes of mouse ADSCs. JAM-C but not JAM-B was broadly distributed in the interstitial spaces of mouse adipose tissue. Interestingly, the JAM-C ectodomain was cleaved and secreted as a soluble form (sJAM-C) in vitro and in vivo, leading to deposition in the fat interstitial tissue. When ADSCs were grown in culture plates coated with sJAM-C, cell adhesion, cell proliferation and the expression of five mesenchymal stem cell markers, Cd44, Cd105, Cd140a, Cd166 and Sca-1, were significantly elevated. Moreover, immunoprecipitation assay showed that sJAM-C formed a complex with JAM-B. Using CRISPR/Cas9-based genome editing, we also demonstrated that sJAM-C was coupled with JAM-B to stimulate ADSC adhesion and maintenance. Together, these findings provide insight into the unique function of sJAM-C in ADSCs. We propose that JAMs contribute not only to cell–cell adhesion, but also to cell–matrix adhesion, by excising their ectodomain and functioning as a niche-like microenvironment for stem and progenitor cells.

Macrophage migration inhibitory factor (MIF) promotes cell survival and proliferation of neural stem/progenitor cells

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Cell Survival ◽  
Progenitor Cells ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Ganglionic Eminence ◽  
Neural Stem Progenitor Cells

In a previous study, we showed that murine dendritic cells (DCs) can increase the number of neural stem/progenitor cells (NSPCs) in vitroand in vivo. In the present study, we identified macrophage migration inhibitory factor (MIF) as a novel factor that can support theproliferation and/or survival of NSPCs in vitro. MIF is secreted by DCs and NSPCs, and its function in the normal brain remains largelyunknown. It was previously shown that in macrophages, MIF binds to a CD74–CD44 complex. In the present study, we observed theexpression of MIF receptors in mouse ganglionic-eminence-derived neurospheres using flow cytometry in vitro. We also found CD74expression in the ganglionic eminence of E14 mouse brains, suggesting that MIF plays a physiological role in vivo. MIF increased thenumber of primary and secondary neurospheres. By contrast, retrovirally expressed MIF shRNA and MIF inhibitor (ISO-1) suppressedprimary and secondary neurosphere formation, as well as cell proliferation. In the neurospheres, MIF knockdown by shRNA increasedcaspase 3/7 activity, and MIF increased the phosphorylation of Akt, Erk, AMPK and Stat3 (Ser727), as well as expression of Hes3 and Egfr,the products of which are known to support cell survival, proliferation and/or maintenance of NSPCs. MIF also acted as a chemoattractantfor NSPCs. These results show that MIF can induce NSPC proliferation and maintenance by multiple signaling pathways actingsynergistically, and it may be a potential therapeutic factor, capable of activating NSPC, for the treatment of degenerative brain disorders.

scholarly journals Direct Stimulation of Adult Neural Stem/Progenitor Cells In Vitro and Neurogenesis In Vivo by Salvianolic Acid B

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e35636 ◽  
Author(s):  
Pengwei Zhuang ◽  
Yanjun Zhang ◽  
Guangzhi Cui ◽  
Yuhong Bian ◽  
Mixia Zhang ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Salvianolic Acid B ◽  
Direct Stimulation ◽  
Salvianolic Acid ◽  
Neural Stem Progenitor Cells ◽  
Stimulation Of

scholarly journals Neural Stem/Progenitor Cells Promote Endothelial Cell Morphogenesis and Protect Endothelial Cells against Ischemia via HIF-1α-Regulated VEGF Signaling

2008 ◽  
Vol 28 (9) ◽  
pp. 1530-1542 ◽  
Author(s):  
Tamara Roitbak ◽  
Lu Li ◽  
Lee Anna Cunningham
Keyword(s):  
Endothelial Cell ◽  
Progenitor Cells ◽  
Adult Brain ◽  
Serum Starvation ◽  
Protective Effects ◽  
Embryonic Mouse ◽  
Vegf Signaling ◽  
Intracerebral Transplantation ◽  
Neural Stem Progenitor Cells

Vascular cells provide a neural stem/progenitor cell (NSPC) niche that regulates expansion and differentiation of NSPCs within the germinal zones of the embryonic and adult brain under both physiologic and pathologic conditions. Here, we examined the NSPC—endothelial cell (NSPC/EC) interaction under conditions of ischemia, both in vitro and after intracerebral transplantation. In culture, embryonic mouse NSPCs supported capillary morphogenesis and protected ECs from cell death induced by serum starvation or by transient oxygen and glucose deprivation (OGD). Neural stem/progenitor cells constitutively expressed hypoxia-inducible factor 1α (HIF-1α) transcription factor and vascular endothelial growth factor (VEGF), both of which were increased approximately twofold after the exposure of NSPCs to OGD. The protective effects of NSPCs on ECs under conditions of serum starvation and hypoxia were blocked by pharmacological inhibitors of VEGF signaling, SU1498 and Flt-1-Fc. After intracerebral transplantation, NSPCs continued to express HIF-1α and VEGF, and promoted microvascular density after focal ischemia. These studies support a role for NSPCs in stabilization of vasculature during ischemia, mediated via HIF-1α-VEGF signaling pathways, and suggest therapeutic application of NSPCs to promote revascularization and repair after brain injury.

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