Neuronal Cell Differentiation Research Articles

Neuronal and muscle differentiation of mammalian cells is accompanied by a change of PHF10 isoform expression

Neuronal and muscle differentiation of mammalian cells is accompanied by a change of PHF10 isoform expression

Dopamine-Functionalized, Red Carbon Quantum Dots for In Vivo Bioimaging, Cancer Therapeutics, and Neuronal Differentiation.

One of the crucial requirements of quantum dots for biological applications is their surface modification for very specific and enhanced biological recognition and uptake. Toward this end, we present the green synthesis of bright, red-emitting carbon quantum dots derived from mango leaf extract (mQDs). These mQDs are conjugated electrostatically with dopamine to form mQDs-dopamine (mQDs:DOPA) bioconjugates. Bright-red fluorescence of mQDs was used for bioimaging and uptake in cancerous and noncancerous cell lines, tissues, and in vivo models like zebrafish. mQDs exhibited the highest uptake in brain tissue compared to the heart, kidney, and liver. mQD:DOPA conjugates killed breast cancer cells and increased uptake in epithelial RPE-1 cells and zebrafish. Additionally, mQDs:DOPA promoted neuronal differentiation of SH-SY5Y cells to differentiated neurons. Both mQDs and mQDs:DOPA exhibited the potential for higher collective cell migrations, implicating their future potential as next-generation tools for advanced biological and biomedical applications.

Pan-Cancer Analysis and Experimental Validation of CEND1 as a Prognostic and Immune Infiltration-Associated Biomarker for Gliomas.

Cell cycle exit and neuronal differentiation 1 (CEND1), highly expressed in the brain, is a specific transmembrane protein which plays a tumor suppressor role. This study is performed to investigate the role of CEND1 in various cancers through pan-cancer analysis, and further investigate its functions in gliomas by cell experiments. The expression and subcellular localization of CEND1 in different cancer types were analyzed utilizing the data from the GEPIA, UCSC, UALCAN and HPA databases. Relationships of CEND1 expression with prognosis, immunomodulation-related genes, immune checkpoint genes, microsatellite instability (MSI), tumor mutation burden (TMB) and RNA modifications were analyzed based on the TCGA database. The ESTIMATE algorithm was utilized to evaluate tumors' StromalScore, Immune Score, and ESTIMATES Score. The cBioPortal database was employed to analyze the categories and frequencies of CEND1 gene alterations. Biological functions and co-expression patterns of CEND1 in gliomas were explored using the LinkedOmics database, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted. The interactions between CEND1 and drugs were explored employing the Comparative Toxicogenomics Database and molecular docking technology. Cell experiments were conducted to analyze triptonide's effects on glioma cells through CCK-8, flow cytometry and qRT-PCR. CEND1 was lowly expressed in gliomas, and high CEND1 expression was correlated to better overall survival of glioma patients (HR = 0.65, P = 0.02). Deep deletion was the main type of hereditary change of CEND1 mutation. CEND1 expression was markedly associated with immune infiltration, TMB, MSI, and RNA modification in various tumors (r > 0.3, P < 0.05). CEND1 co-expressed genes in gliomas were markedly correlated with immune responses and cell cycle (FDR < 0.05). Triptonide could bind well to CEND1 (-5.0kcal/mol), and triptonide could facilitate CEND1 expression in glioma cells and cell apoptosis, and block the cell cycle progression (P < 0.05). CEND1 serves as a potential biomarker for pan-cancer. Particularly in gliomas, CEND1 is a key regulator of cell apoptosis and cell cycle, and a potential target for glioma treatment.

A novel mutation of DNA2 regulates neuronal cell membrane potential and epileptogenesis.

Mesial temporal lobe epilepsy (MTLE) is one of the most intractable epilepsies. Previously, we reported that mitochondrial DNA deletions were associated with epileptogenesis. While the underlying mechanism of mitochondrial DNA deletions during epileptogenesis remain unknown. In this study, a novel somatic mutation of DNA2 gene was identified in the hippocampal tissue of two MTLE patients carrying mitochondrial DNA deletions, and this mutation decreased the full-length expression of DNA2 protein significantly, aborting its normal functions. Then, we knocked down the DNA2 protein in zebrafish, and we demonstrated that zebrafish with DNA2 deficiency showed decreased expression of mitochondrial complex II-IV, and exhibited hallmarks of epileptic seizures, including abnormal development of the zebrafish and epileptiform discharge signals in brain, compared to the Cas9-control group. Moreover, our cell-based assays showed that DNA2 deletion resulted in accumulated mitochondrial DNA damage, abnormal oxidative phosphorylation and decreased ATP production in cells. Inadequate ATP generation in cells lead to declined Na+, K+-ATPase activity and change of cell membrane potential. Together, these disorders caused by DNA2 depletion increased cell apoptosis and inhibited the differentiation of SH-SY5Y into branched neuronal phenotype. In conclusion, DNA2 deficiency regulated the cell membrane potential via affecting ATP production by mitochondria and Na+, K+-ATPase activity, and also affected neuronal cell growth and differentiation. These disorders caused by DNA2 dysfunction are important causes of epilepsy. In summary, we are the first to report the pathogenic somatic mutation of DNA2 gene in the patients with MTLE disease, and we uncovered the mechanism of DNA2 regulating the epilepsy. This study provides new insight into the pathogenesis of epilepsy and underscore the value of DNA2 in epilepsy.

Selective targeting of IRAK1 attenuates low molecular weight hyaluronic acid-induced stemness and non-canonical STAT3 activation in epithelial ovarian cancer

Advanced epithelial ovarian cancer (EOC) survival rates are dishearteningly low, with ~25% surviving beyond 5 years. Evidence suggests that cancer stem cells contribute to acquired chemoresistance and tumor recurrence. Here, we show that IRAK1 is upregulated in EOC tissues, and enhanced expression correlates with poorer overall survival. Moreover, low molecular weight hyaluronic acid, which is abundant in malignant ascites from patients with advanced EOC, induced IRAK1 phosphorylation leading to STAT3 activation and enhanced spheroid formation. Knockdown of IRAK1 impaired tumor growth in peritoneal disease models, and impaired HA-induced spheroid growth and STAT3 phosphorylation. Finally, we determined that TCS2210, a known inducer of neuronal differentiation in mesenchymal stem cells, is a selective inhibitor of IRAK1. TCS2210 significantly inhibited EOC growth in vitro and in vivo both as monotherapy, and in combination with cisplatin. Collectively, these data demonstrate IRAK1 as a druggable target for EOC.

PLCβ1 by-passes early growth response -1 to induce the differentiation of neuronal cells

The Gαq/phospholipase C-β (PLCβ) signaling system mediates calcium responses to a variety of hormones and neurotransmitters. Recent studies suggest that PLCβ1 expression plays a role in the differentiation of two types of cultured neuronal cells (PC12 and SK-N-SH) through a mechanism independent of Gαq. Here, we show that, similar to that observed in PC12 and SK-N-SH cells, PLCβ1 expression increases when human NT2 cells are induced to differentiate either through cytosine-β-D-arabinofuranoside or retinoic acid. Preventing this increase, abolishes differentiation, and down-regulating PLCβ1 in rat primary astrocytes causes cells to adapt an undifferentiated morphology. Surprisingly, transfecting PLCβ1 into undifferentiated PC12 or NT2 cells induces differentiation without the need for differentiating agents. Studies to uncover the underlying mechanism focused on the transcription factor early growth response 1 (Egr-1) which mediates PLCβ1 expression early in differentiation. Over-expressing PLCβ1 in HEK293 cells enhances Egr-1 expression and induces morphological changes. We show that increased levels of cytosolic PLCβ1 in undifferentiated PC12 cells disrupts the association between Egr-1 and its cytosolic binding partner (Tar RNA binding protein), promoting relocalization of Egr-1 to the nucleus, which promotes transcription of proteins needed for differentiation. These studies show a novel mechanism through which differentiation can be modulated.

Viscoelastic cues to induce stem cell migration and neuronal differentiation in cell-free hydrogel-assisted TBI recovery

The concept of tissue-inducing biomaterials, such as osteoinductive biomaterials, has inspired the design of regenerative material with biomimetic cues to manipulate cell/tissue responses but has been little applied for neuroinduction in traumatic brain injury (TBI) treatment. Meanwhile, material design has typically focused on elasticity without viscoelasticity taken into consideration. Here, guided by the intrinsic viscoelasticity of brain tissue and the decisive role of viscoelasticity in cell-matrix interactions, we developed a family of brain-mimicking hydrogels, in which the viscoelasticity can be tuned over a wide range under the premise that hydrogels have a low modulus comparable to that of brain tissue. Then, we revealed the promoted migration of stem cells on the viscoelastic hydrogel resulted from the increased number of motor − clutch pairs and filopodia protrusions, as well as their enhanced neuronal differentiation. In a rat TBI model, the cell-free viscoelastic hydrogel successfully induced endogenous stem cells to migrate into lesions and differentiate into neurons, contributing to brain tissue regeneration and neurological function restoration. This study reveals the great promise of biomimetic viscoelastic matrices for TBI treatment, and simultaneously, provides intriguing insights for the design of tissue-inducing biomaterials.

SFlt-1 impairs neurite growth and neuronal differentiation in SH-SY5Y cells and human neurons.

Pre-eclampsia (PE) is a hypertensive disorder of pregnancy which is associated with increased risk of neurodevelopmental disorders in exposed offspring. The pathophysiological mechanisms mediating this relationship are currently unknown, and one potential candidate is the anti-angiogenic factor soluble Fms-like tyrosine kinase 1 (sFlt-1), which is highly elevated in PE. While sFlt-1 can impair angiogenesis via inhibition of VEGFA signalling, it is unclear whether it can directly affect neuronal development independently of its effects on the vasculature. To test this hypothesis, the current study differentiated the human neural progenitor cell (NPC) line ReNcell® VM into a mixed culture of mature neurons and glia, and exposed them to sFlt-1 during development. Outcomes measured were neurite growth, cytotoxicity, mRNA expression of nestin, MBP, GFAP, and βIII-tubulin, and neurosphere differentiation. sFlt-1 induced a significant reduction in neurite growth and this effect was timing- and dose-dependent up to 100 ng/ml, with no effect on cytotoxicity. sFlt-1 (100 ng/ml) also reduced βIII-tubulin mRNA and neuronal differentiation of neurospheres. Undifferentiated NPCs and mature neurons/glia expressed VEGFA and VEGFR-2, required for endogenous autocrine and paracrine VEGFA signalling, while sFlt-1 treatment prevented the neurogenic effects of exogenous VEGFA. Overall, these data provide the first experimental evidence for a direct effect of sFlt-1 on neurite growth and neuronal differentiation in human neurons through inhibition of VEGFA signalling, clarifying our understanding of the potential role of sFlt-1 as a mechanism by which PE can affect neuronal development.

CLOCK evolved in cnidaria to synchronize internal rhythms with diel environmental cues

CLOCK evolved in cnidaria to synchronize internal rhythms with diel environmental cues

CLOCK evolved in cnidaria to synchronize internal rhythms with diel environmental cues.

The circadian clock enables anticipation of the day/night cycle in animals ranging from cnidarians to mammals. Circadian rhythms are generated through a transcription-translation feedback loop (TTFL or pacemaker) with CLOCK as a conserved positive factor in animals. However, CLOCK's functional evolutionary origin and mechanism of action in basal animals are unknown. In the cnidarian Nematostella vectensis, pacemaker gene transcript levels, including NvClk (the Clock ortholog), appear arrhythmic under constant darkness, questioning the role of NvCLK. Utilizing CRISPR/Cas9, we generated a NvClk allele mutant (NvClkΔ), revealing circadian behavior loss under constant dark (DD) or light (LL), while maintaining a 24 hr rhythm under light-dark condition (LD). Transcriptomics analysis revealed distinct rhythmic genes in wild-type (WT) polypsunder LD compared to DD conditions. In LD, NvClkΔ/Δ polyps exhibited comparable numbers of rhythmic genes, but were reduced in DD. Furthermore, under LD, the NvClkΔ/Δ polyps showed alterations in temporal pacemaker gene expression, impacting their potential interactions. Additionally, differential expression of non-rhythmic genes associated with cell division and neuronal differentiation was observed. These findings revealed that a light-responsive pathway can partially compensate for circadian clock disruption, and that the Clock gene has evolved in cnidarians to synchronize rhythmic physiology and behavior with the diel rhythm of the earth's biosphere.

Salidroside promotes the repair of spinal cord injury by inhibiting astrocyte polarization, promoting neural stem cell proliferation and neuronal differentiation

Spinal cord injury (SCI) remains a formidable challenge, lacking effective treatments. Following SCI, neural stem cells (NSCs) migrate to SCI sites, offering a potential avenue for nerve regeneration, but the effectiveness of this intrinsic repair mechanism remains suboptimal. Salidroside has demonstrated pro-repair attributes in various pathological conditions, including arthritis and cerebral ischemia, and the ability to curtail early-stage inflammation following SCI. However, the specific role of salidroside in the late-stage repair processes of SCI remains less defined. In this investigation, we observed that continuous salidroside treatment in SCI mice improved motor function recovery. Immunofluorescence-staining corroborated salidroside’s capacity to stimulate nerve regeneration and remyelination, suppress glial scar hyperplasia, reduce the activation of neurotoxic A1 astrocytes, and facilitate NSCs migration towards the injured region. Mechanistically, in vitro experiments elucidated salidroside’s significant role in restraining astrocyte proliferation and A1 polarization. It was further established that A1 astrocytes hinder NSCs proliferation while inducing their differentiation into astrocytes. Salidroside effectively ameliorated this inhibition of NSCs proliferation through diminishing c-Jun N-terminal kinase (JNK) pathway phosphorylation and restored their differentiation into neurons by suppressing the signal transducer and activator of transcription 3 (STAT3) pathway. In summary, our findings suggest that salidroside holds promise as a therapeutic agent for traumatic SCI treatment.

EFA6A, an Exchange Factor for Arf6, Regulates NGF-Dependent TrkA Recycling From Early Endosomes and Neurite Outgrowth in PC12 Cells.

Endosomal trafficking of TrkA is a critical process for nerve growth factor (NGF)-dependent neuronal cell survival and differentiation. The small GTPase ADP-ribosylation factor 6 (Arf6) is implicated in NGF-dependent processes in PC12 cells through endosomal trafficking and actin cytoskeleton reorganization. However, the regulatory mechanism for Arf6 in NGF signaling is largely unknown. In this study, we demonstrated that EFA6A, an Arf6-specific guanine nucleotide exchange factor, was abundantly expressed in PC12 cells and that knockdown of EFA6A significantly inhibited NGF-dependent Arf6 activation, TrkA recycling from early endosomes to the cell surface, prolonged ERK1/2 phosphorylation, and neurite outgrowth. We also demonstrated that EFA6A forms a protein complex with TrkA through its N-terminal region, thereby enhancing its catalytic activity for Arf6. Similarly, we demonstrated that EFA6A forms a protein complex with TrkA in cultured dorsal root ganglion (DRG) neurons. Furthermore, cultured DRG neurons from EFA6A knockout mice exhibited disturbed NGF-dependent TrkA trafficking compared with wild-type neurons. These findings provide the first evidence for EFA6A as a key regulator of NGF-dependent TrkA trafficking and signaling.

Alternative splicing of a chromatin modifier alters the transcriptional regulatory programs of stem cell maintenance and neuronal differentiation

Development of embryonic stem cells (ESCs) into neurons requires intricate regulation of transcription, splicing, and translation, but how these processes interconnect is not understood. We found that polypyrimidine tract binding protein 1 (PTBP1) controls splicing of DPF2, a subunit of BRG1/BRM-associated factor (BAF) chromatin remodeling complexes. Dpf2 exon 7 splicing is inhibited by PTBP1 to produce the DPF2-S isoform early in development. During neuronal differentiation, loss of PTBP1 allows exon 7 inclusion and DPF2-L expression. Different cellular phenotypes and gene expression programs were induced by these alternative DPF2 isoforms. We identified chromatin binding sites enriched for each DPF2 isoform, as well as sites bound by both. In ESC, DPF2-S preferential sites were bound by pluripotency factors. In neuronal progenitors, DPF2-S sites were bound by nuclear factor I (NFI), while DPF2-L sites were bound by CCCTC-binding factor (CTCF). DPF2-S sites exhibited enhancer modifications, while DPF2-L sites showed promoter modifications. Thus, alternative splicing redirects BAF complex targeting to impact chromatin organization during neuronal development.

Metformin inhibits nerve growth factor-induced sympathetic neuron differentiation through p35/CDK5 inhibition.

The authors' previous research has shown the pivotal roles of cyclin-dependent kinase 5 (CDK5) and its regulatory protein p35 in nerve growth factor (NGF)-induced differentiation of sympathetic neurons in PC12 cells. During the process of differentiation, neurons are susceptible to environmental influences, including the effects of drugs. Metformin is commonly used in the treatment of diabetes and its associated symptoms, particularly in diabetic neuropathy, which is characterized by dysregulation of the sympathetic neurons. However, the impacts of metformin on sympathetic neuronal differentiation remain unknown. In this study, we investigated the impact of metformin on NGF-induced sympathetic neuronal differentiation using rat pheochromocytoma PC12 cells as a model. We examined the regulation of TrkA-p35/CDK5 signaling in NGF-induced PC12 differentiation. Our results demonstrate that metformin reduces NGF-induced PC12 differentiation by inactivating the TrkA receptor, subsequently inhibiting ERK and EGR1. Inhibition of this cascade ultimately leads to the downregulation of p35/CDK5 in PC12 cells. Furthermore, metformin inhibits the activation of the presynaptic protein Synapsin-I, a substrate of CDK5, in PC12 differentiation. In addition, metformin alters axonal and synaptic bouton formation by inhibiting p35 at both the axons and axon terminals in fully differentiated PC12 cells. In summary, our study elucidates that metformin inhibits sympathetic neuronal differentiation in PC12 cells by disrupting TrkA/ERK/EGR1 and p35/CDK5 signaling. This research contributes to uncovering a novel signaling mechanism in drug response during sympathetic neuronal differentiation, enhancing our understanding of the intricate molecular processes governing this critical aspect of neurodevelopment.NEW & NOTEWORTHY This study unveils a novel mechanism influenced by metformin during sympathetic neuronal differentiation. By elucidating its inhibitory effects from the nerve growth factor (NGF) receptor, TrkA, to the p35/CDK5 signaling pathways, we advance our understanding of metformin's mechanisms of action and emphasize its potential significance in the context of drug responses during sympathetic neuronal differentiation.

Biological Implications and Functional Significance of Transglutaminase Type 2 in Nervous System Tumors.

Transglutaminase type 2 (TG2) is the most ubiquitously expressed member of the transglutaminase family. TG2 catalyzes the transamidation reaction leading to several protein post-translational modifications and it is also implicated in signal transduction thanks to its GTP binding/hydrolyzing activity. In the nervous system, TG2 regulates multiple physiological processes, such as development, neuronal cell death and differentiation, and synaptic plasticity. Given its different enzymatic activities, aberrant expression or activity of TG2 can contribute to tumorigenesis, including in peripheral and central nervous system tumors. Indeed, TG2 dysregulation has been reported in meningiomas, medulloblastomas, neuroblastomas, glioblastomas, and other adult-type diffuse gliomas. The aim of this review is to provide an overview of the biological and functional relevance of TG2 in the pathogenesis of nervous system tumors, highlighting its involvement in survival, tumor inflammation, differentiation, and in the resistance to standard therapies.

Harnessing developmental dynamics of spinal cord extracellular matrix improves regenerative potential of spinal cord organoids

Neonatal spinal cord tissues exhibit remarkable regenerative capabilities as compared to adult spinal cord tissues after injury, but the role of extracellular matrix (ECM) in this process has remained elusive. Here, we found that early developmental spinal cord had higher levels of ECM proteins associated with neural development and axon growth, but fewer inhibitory proteoglycans, compared to those of adult spinal cord. Decellularized spinal cord ECM from neonatal (DNSCM) and adult (DASCM) rabbits preserved these differences. DNSCM promoted proliferation, migration, and neuronal differentiation of neural progenitor cells (NPCs) and facilitated axonal outgrowth and regeneration of spinal cord organoids more effectively than DASCM. Pleiotrophin (PTN) and Tenascin (TNC) in DNSCM were identified as contributors to these abilities. Furthermore, DNSCM demonstrated superior performance as a delivery vehicle for NPCs and organoids in spinal cord injury (SCI) models. This suggests that ECM cues from early development stages might significantly contribute to the prominent regeneration ability in spinal cord.

Brain neurotrophic factor BDNF: new data, functions and questions

The brain-derived neurotrophic factor (BDNF) is a key modulator of neurogenesis, synaptogenesis, neuroregeneration, and cell differentiation in the nervous system. Impaired BDNF functioning is a characteristic of various neurological diseases, such as Alzheimer’s disease, multiple sclerosis, and depressive disorders. There is recent evidence that patients with COVID-19 have reduced BDNF levels in the blood plasma. Furthermore, exogenous BDNF and its mimetics have demonstrated therapeutic potential.&#x0D; In this review, we systematized data of the BDNF gene structure, epigenetic and microRNA-mediated regulation of its expression, transcriptional variants of BDNF, and the effects of BDNF on neuronal and oligodendroglial differentiation. Further, we point out the gaps in the current knowledge about BDNF and propose experiments that can expand such knowledge and the range of possibilities for using BDNF in biomedicine. These include determining the expression pattern of all BDNF gene transcripts at different stages of differentiation and in different cell subpopulations and studying the role of receptor-independent BDNF signaling, circadian fluctuations in BDNF levels, and their role in physiological and pathophysiological conditions. Finally, for translational medicine, evaluating the effect of BDNF mimetics (including those immobilized on three-dimensional scaffolds for tissue engineering) on neuronal and oligodendroglial differentiation of pluripotent and polypotent cells and identifying molecular regulators of BDNF transcription, including small molecules and microRNAs capable of regulating BDNF gene expression, are crucial.

Endoplasmic reticulum stress and death receptor-mediated apoptosis in the neuronal differentiation of adult adipose-derived stromal cells

Apoptosis is the primary cause of cell death in the differentiation of Adipose-derived stromal cells (ADSCs) into neurons. However, the relationship between endoplasmic reticulum stress (ERS) and death receptor-mediated apoptosis in ADSC-induced neuronal differentiation is not clear. ADSCs were isolated and induced to differentiate into neurons using β-mercaptoethanol. The expression of neuron-specific enolase (NSE), GRP94, CHOP, Fas/FasL, TNFR1/TNF-α, DR5/TRAIL, Caspase8, and Caspase3 in ADSCs was examined using immunocytochemistry and Western blotting before induction, during pre-induction, and after induction. Transmission electron microscopy (TEM) was used to observe changes in the morphology of the endoplasmic reticulum (ER), and the MTT assay was employed to measure cell viability in the uninduced and induced groups. Additionally, the number of apoptotic cells during the induction process was measured using flow cytometry with Annexin V/PI. With increasing induction time, the positive expression rates of CHOP, Fas/FasL, Caspase8, Caspase-3, and NSE gradually increased, while the positive expression rate of GRP94 decreased. TNFR1/TNF-α and DR5/TRAIL peaked at 5 h post-induction and then decreased at 8 h. TEM revealed swelling and expansion of the ER, vacuolar changes, and degranulation in cells. The MTT assay showed a gradual decrease in the absorbance of surviving cells in all groups. Flow cytometry indicated an increasing rate of apoptosis in cells. Therefore, ERS in the normal culture and growth of ADSCs, manifesting as enhanced unfolded protein response (UPR), maintains the normal survival of ADSCs. However, in the process of ADSC-induced differentiation into neurons, ERS and death receptor-mediated apoptosis are significant causes of cell death.

Platelet-Activating Factor Receptor (PAFR) Regulates Retinal Progenitor/Stem Cells Profile in Ciliary Epithelium Cells.

The retina is a central nervous tissue essential to visual perception and highly susceptible to environmental damage. Lower vertebrate retinas activate intrinsic regeneration mechanisms in response to retinal injury regulated by a specialized population of progenitor cells. The mammalian retina does not have populations of progenitor/stem cells available to activate regeneration, but contains a subpopulation of differentiated cells that can be reprogrammed into retinal stem cells, the ciliary epithelium (CE) cells. Despite the regenerative potential, stem cells derived from CE exhibit limited reprogramming capacity probably associated with the expression of intrinsic regulatory mechanisms. Platelet-activating factor (PAF) is a lipid mediator widely expressed in many cells and plays an important role in stem cell proliferation and differentiation. During mammalian development, PAF receptor signaling showed important effects on retinal progenitors' cell cycle regulation and neuronal differentiation that need to be further investigated. In this study, our findings suggested a dynamic role for PAF receptor signaling in CE cells, impacting stem cell characteristics and neurosphere formation. We showed that PAF receptors and PAF-related enzymes are downregulated in retinal progenitor/stem cells derived from PE cells. Blocking PAFR activity using antagonists increased the expression of specific progenitor markers, revealing potential implications for retinal tissue development and maintenance.

Mild hypothermia promotes neuronal differentiation of human neural stem cells via RBM3-SOX11 signaling pathway

Mild hypothermia promotes neuronal differentiation of human neural stem cells via RBM3-SOX11 signaling pathway