Abstract：
:Tuberous sclerosis complex (TSC) is a genetic disease affecting the brain. Neurological symptoms like epilepsy and neurodevelopmental issues cause a significant burden on patients. Both neurons and glial cells are affected by TSC mutations. Previous studies have shown changes in the excitation/inhibition balance (E/I balance) in TSC. Astrocytes are known to be important for neuronal development, and astrocytic dysfunction can cause changes in the E/I balance. We hypothesized that astrocytes affect the synaptic balance in TSC. TSC patient-derived stem cells were differentiated into astrocytes, which showed increased proliferation compared to control astrocytes. RNA sequencing revealed changes in gene expression, which were related to epidermal growth factor (EGF) signaling and enriched for genes that coded for secreted or transmembrane proteins. Control neurons were cultured in astrocyte-conditioned medium (ACM) of TSC and control astrocytes. After culture in TSC ACM, neurons showed an altered synaptic balance, with an increase in the percentage of VGAT+ synapses. These findings were confirmed in organoids, presenting a spontaneous 3D organization of neurons and glial cells. To conclude, this study shows that TSC astrocytes are affected and secrete factors that alter the synaptic balance. As an altered E/I balance may underlie many of the neurological TSC symptoms, astrocytes may provide new therapeutic targets.
journal_name
Cellsjournal_title
Cellsauthors
Dooves S,van Velthoven AJH,Suciati LG,Heine VMdoi
10.3390/cells10010134subject
Has Abstractpub_date
2021-01-12 00:00:00issue
1issn
2073-4409pii
cells10010134journal_volume
10pub_type
杂志文章相关文献
Cells文献大全abstract：:Canonical transient receptor potential (TRPC) channels are a family of polymodal cation channels with some degree of Ca2+ permeability. Although initially thought to be channels mediating store-operated Ca2+ influx, TRPC channels can be activated by stimulation of Gq-coupled G-protein coupled receptors, or by an incre...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells3020288
更新日期：2014-04-09 00:00:00
abstract：:Extracellular vesicles (EVs) are involved in intercellular communication during carcinogenesis, and cancer cells are able to secrete EVs, in particular exosomes containing molecules, that can be transferred to recipient cells to induce pathological processes and significant modifications, as metastasis, increase of pr...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8080777
更新日期：2019-07-25 00:00:00
abstract：:The MRE11-RAD50-NBS1 (MRN) protein complex is one of the primary vehicles for repairing DNA double strand breaks and maintaining the genomic stability within the cell. The role of the MRN complex to recognize and process DNA double-strand breaks as well as signal other damage response factors is critical for maintaini...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9071678
更新日期：2020-07-13 00:00:00
abstract：:Increasing evidence suggests that metabolic alterations may be etiologically linked to neurodegenerative disorders such as Parkinson's disease (PD) and in particular empathizes the possibility of targeting mitochondrial dysfunctions to improve PD progression. Under different pathological conditions (i.e., cardiac and ...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9092037
更新日期：2020-09-06 00:00:00
abstract：:An outbreak of the novel coronavirus (CoV) SARS-CoV-2, the causative agent of COVID-19 respiratory disease, infected millions of people since the end of 2019, led to high-level morbidity and mortality and caused worldwide social and economic disruption. There are currently no antiviral drugs available with proven effi...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9091962
更新日期：2020-08-25 00:00:00
abstract：:Insulin and insulin-like growth factor-1 (IGF1) have important roles in breast cancer development. The recent identification of nuclear insulin (INSR) and IGF1 (IGF1R) receptors provides a novel paradigm in the area of signal transduction. The fact that INSR and IGF1R can function as transcription factors, capable of ...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8121499
更新日期：2019-11-23 00:00:00
abstract：:Lipid exchange among biological membranes, lipoprotein particles, micelles, and liposomes is an important yet underrated phenomenon with repercussions throughout the life sciences. The premature loss of lipid molecules from liposomal formulations severely impacts therapeutic applications of the latter and thus limits ...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9102213
更新日期：2020-09-29 00:00:00
abstract：:Hepatic fibrosis is the consequence of an unresolved wound healing process in response to chronic liver injury and involves multiple cell types and molecular mechanisms. The hepatic endocannabinoid and apelin systems are two signalling pathways with a substantial role in the liver fibrosis pathophysiology-both are upr...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells8111311
更新日期：2019-10-24 00:00:00
abstract：:Heat shock proteins (HSPs) constitute a large family of molecular chaperones classified by their molecular weights, and they include HSP27, HSP40, HSP60, HSP70, and HSP90. HSPs function in diverse physiological and protective processes to assist in maintaining cellular homeostasis. In particular, HSPs participate in p...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9010060
更新日期：2019-12-24 00:00:00
abstract：:HSPA8/HSC70 is a molecular chaperone involved in a wide variety of cellular processes. It plays a crucial role in protein quality control, ensuring the correct folding and re-folding of selected proteins, and controlling the elimination of abnormally-folded conformers and of proteins daily produced in excess in our ce...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells8080849
更新日期：2019-08-07 00:00:00
abstract：:Differentiation therapy is an alternative strategy used to induce the differentiation of blast cells toward mature cells and to inhibit tumor cell proliferation for cancer treatment. Nobiletin (NOB), a polymethoxyflavone phytochemical, is present abundantly in citrus peels and has been reported to possess anti-cancer ...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9040877
更新日期：2020-04-03 00:00:00
abstract：:Mast cells are long-lived, granular, myeloid-derived leukocytes that have significant protective and repair functions in tissues. Mast cells sense disruptions in the local microenvironment and are first responders to physical, chemical and biological insults. When activated, mast cells release growth factors, protease...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9122713
更新日期：2020-12-18 00:00:00
abstract：:As sessile organisms, plants must adjust their growth to withstand several environmental conditions. The root is a crucial organ for plant survival as it is responsible for water and nutrient acquisition from the soil and has high phenotypic plasticity in response to a lack or excess of them. How plants sense and tran...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9122576
更新日期：2020-12-01 00:00:00
abstract：:The pursuit of matrix metalloproteinase (MMP) inhibitors began in earnest over three decades ago. Initial clinical trials were disappointing, resulting in a negative view of MMPs as therapeutic targets. As a better understanding of MMP biology and inhibitor pharmacokinetic properties emerged, it became clear that init...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells8090984
更新日期：2019-08-27 00:00:00
abstract：:Approximately 3 × 1017 DNA damage events take place per hour in the human body. Within clustered DNA lesions, they pose a serious problem for repair proteins, especially for iron-sulfur glycosylases (MutyH), which can recognize them by the electron-transfer process. It has been found that the presence of both 5',8-cyc...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9020424
更新日期：2020-02-12 00:00:00
abstract：:Mammalian Pumilio (PUM) proteins are sequence-specific, RNA-binding proteins (RBPs) with wide-ranging roles. They are involved in germ cell development, which has functional implications in development and fertility. Although human PUM1 and PUM2 are closely related to each other and recognize the same RNA binding moti...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9040984
更新日期：2020-04-16 00:00:00
abstract：:Notch receptors are single-pass transmembrane proteins that play a critical role in cell fate decisions and have been implicated in the regulation of many developmental processes. The human Notch family comprises of four receptors (Notch 1 to 4) and five ligands. Their signaling can regulate extremely basic cellular p...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells10010016
更新日期：2020-12-24 00:00:00
abstract：:The survival of most patients with advanced stage non-small cell lung cancer is prolonged by several months when they are treated with first- and next-generation inhibitors targeting ALK rearrangements, but resistance inevitably emerges. Some of the mechanisms of resistance are sensitive to novel ALK inhibitors but af...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells10010168
更新日期：2021-01-15 00:00:00
abstract：:The role of kinases in the regulation of cell cycle transitions is very well established, however, over the past decade, studies have identified the ever-growing importance of phosphatases in these processes. It is well-known that an intact or otherwise non-deformed nuclear envelope (NE) is essential for maintaining h...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells8070687
更新日期：2019-07-07 00:00:00
abstract：:Feline coronavirus is a highly contagious virus potentially resulting in feline infectious peritonitis (FIP), while the pathogenesis of FIP remains not well understood, particularly in the events leading to the disease. A predominant theory is that the pathogenic FIPV arises from a mutation, so that it could replicate...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9061431
更新日期：2020-06-09 00:00:00
abstract：:Xeroderma Pigmentosum (XP) is a DNA repair disease characterized by nucleotide excision repair (NER) malfunction, leading to photosensitivity and increased incidence of skin malignancies. The role of XP-A in NER pathways has been well studied while discrepancies associated with ROS levels and the role of radical speci...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8111377
更新日期：2019-11-01 00:00:00
abstract：:The aim of this study was to compare the acute effects of thrombin and brain-derived neurotrophic factor (BDNF) on spontaneous miniature endplate potentials (MEPPs) and multiquantal evoked endplate potentials (EPPs) in mouse neuromuscular junctions (NMJs) of m. diaphragma and m. EDL. Intracellular microelectrode recor...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8070762
更新日期：2019-07-22 00:00:00
abstract：:To identify novel oncogenic targets in head and neck squamous cell carcinoma (HNSCC), we have analyzed antitumor microRNAs (miRNAs) and their controlled molecular networks in HNSCC cells. Based on our miRNA signature in HNSCC, both strands of the miR-99a-duplex (miR-99a-5p: the guide strand, and miR-99a-3p: the passen...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8121535
更新日期：2019-11-28 00:00:00
abstract：:The important role of microRNAs (miRNAs) in the formation, development, diagnosis, and treatment of diseases has attracted much attention among researchers recently. In this study, we present an unsupervised deep learning model of the variational autoencoder for MiRNA-disease association prediction (VAEMDA). Through c...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8091040
更新日期：2019-09-06 00:00:00
abstract：OBJECTIVES:Synovial fluids of rheumatoid arthritis (RA) patients commonly contain high concentrations of soluble CD14 (sCD14). To investigate its potential role in RA pathogenesis, we tested whether sCD14 binding transmits a signal to fibroblast-like synoviocytes from RA patients (RA-FLS). METHODS:The induction of pro...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9071689
更新日期：2020-07-14 00:00:00
abstract：:Tumor recurrence after radiotherapy due to the presence of breast cancer stem cells (BCSCs) is a clinical challenge, and the mechanism remains unclear. Low levels of ROS and enhanced antioxidant defenses are shown to contribute to increasing radioresistance. However, the role of Nrf2-Keap1-Bach1 signaling in the radio...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells10010083
更新日期：2021-01-06 00:00:00
abstract：:In the last few decades, the epithelial cell adhesion molecule (EpCAM) has received increased attention as the main membrane marker used in many enrichment technologies to isolate circulating tumor cells (CTCs). Although there has been a great deal of progress in the implementation of EpCAM-based CTC detection technol...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9081836
更新日期：2020-08-05 00:00:00
abstract：:Nuclear lamins (NLs) are essential components of the animal cell nucleus involved in the regulation of a plethora of molecular and cellular processes. These include the nuclear envelope assembly and stability, mechanotransduction and chromatin organization, transcription, DNA replication, damage repair, and genomic in...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9061340
更新日期：2020-05-27 00:00:00
abstract：:Autophagy is a eukaryotic catabolic pathway that degrades and recycles cellular components to maintain homeostasis. It can target protein aggregates, superfluous biomolecular complexes, dysfunctional and damaged organelles, as well as pathogenic intracellular microbes. Autophagy is a dynamic process in which the diffe...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells6030018
更新日期：2017-07-03 00:00:00
abstract：:Fear is a fundamental evolutionary process for survival. However, excess or irrational fear hampers normal activity and leads to phobia. The amygdala is the primary brain region associated with fear learning and conditioning. There, Rho GTPases are molecular switches that act as signaling molecules for further downstr...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9091972
更新日期：2020-08-26 00:00:00
