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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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At least 469 records · Page 26Linked to original sources

bioRxiv2017

FAM83G/PAWS1 controls cytoskeletal dynamics and cell migration through association with the SH3 adaptor CD2AP

Our previous studies of PAWS1 (Protein Associated With SMAD1) have suggested that this molecule has roles beyond BMP signalling. To investigate these roles, we have used CRISPR/Cas9 to generate PAWS1 knockout cells. Here, we show that PAWS1 plays a role in the regulation of the cytoskeletal machinery, including actin and focal adhesion dynamics, and cell migration. Confocal microscopy and live cell imaging of actin in U2OS cells indicate that PAWS1 is also involved in cytoskeletal dynamics and organization. Loss of PAWS1 causes severe defects in F-actin organization and distribution as well as in lamellipodial organization, resulting in impaired cell migration. PAWS1 interacts in a dynamic fashion with the actin/cytoskeletal regulator CD2AP at lamellae, suggesting that its association with CD2AP controls actin organization and cellular migration.\n\nSummary statementPAWS1/FAM83G controls cell migration by influencing the organisation of F-actin and focal adhesions and the distribution of the actin stress fibre network through its association with CD2AP.

cell biology↗

bioRxiv2017

SIRT3-dependent mitochondrial oxidative stress in sodium fluoride-induced hepatotoxicity and salvage by melatonin

Oxidative stress induced by fluoride (F) is associated with fluorosis formation, but the underlying molecular mechanism remains unclear. In this study, Melatonin pretreatment suppressed F-induced hepatocyte injury in HepG2 cells. Melatonin increases the activity of superoxide dismutase (SOD2) by enhancing sirtuin 3 (SIRT3)-mediated deacetylation and promotes SOD2 gene expression via SIRT3-regulated DNA-binding activity of forkhead box O3 (FoxO3a), indicating that melatonin markedly enhanced mROS scavenging in F-exposed HepG2 cells. Notably, melatonin activated the peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1). PGC-1 interacted with the estrogen-related receptor alpha (ERR) bound to the SIRT3 promoter, where it functions as a transcription factor to regulate SIRT3 expression. Furthermore, daily injection of melatonin for 30 days inhibited F-induced oxidative stress in mice liver, leading to improvement of liver function. Mechanistic study revealed that the protective effects of melatonin were associated with down-regulation of JNK1/2 phosphorylation in vitro and in vivo. Collectively, our data suggest a novel role of melatonin in preventing F-induced oxidative stress through activation of the SIRT3 pathway.

cell biology↗

bioRxiv2017

Function of the Arabidopsis kinesin-4, FRA1, requires abundant processive motility

Processivity is important for kinesins that mediate intracellular transport. Structure-function analyses of N-terminal kinesins have identified several non-motor regions that affect processivity in vitro. However, whether these structural elements affect kinesin processivity and function in vivo is not known. Here, we used an Arabidopsis kinesin-4, called Fragile Fiber1 (FRA1), which is thought to mediate vesicle transport to test whether mutations that alter processivity in vitro behave similarly in vivo and whether processivity is important for FRAs function. We generated several FRA1 mutants that differed in their run lengths in vitro and then transformed them into the fra1-5 mutant for complementation and in vivo motility analyses. Our data show that the behavior of processivity mutants in vivo can differ dramatically from in vitro properties, underscoring the need to extend structure-function analyses of kinesins in vivo. In addition, we found that high density of processive motility is necessary for FRA1s physiological function.\n\nSummaryThis study shows that the motility of kinesin mutants can differ significantly between in vitro and in vivo conditions and that abundant processive motility is important for FRA1 kinesins function.

cell biology↗

bioRxiv2017

The Deubiquitylating Enzyme Ubp12 Regulates Rad23-Dependent Substrate Delivery at the Proteasome

The consecutive actions of the ubiquitin-selective segregase Cdc48 and the ubiquitin shuttle factor Rad23 result in the delivery of ubiquitylated proteins at the proteasome. Here, we show that the deubiquitylating enzyme Ubp12 interacts with Cdc48 and regulates proteasomal degradation of Rad23-dependent substrates. Overexpression of Ubp12 results in stabilization of Rad23-dependent substrates. We show that Ubp12 removes short ubiquitin chains from the N-terminal ubiquitin-like domain (UbL) of Rad23. Preventing ubiquitylation of Rad23 by substitution of lysine residues within the UbL domain, Rad23UbLK0, does not affect the non-proteolytic role of Rad23 in DNA repair but causes an increase in ubiquitylated cargo bound to the UBA2 domains of Rad23 and recapitulates the stabilization of Rad23-dependent substrates observed upon overexpression of Ubp12. Expression of Rad23UbLK0 or overexpression of Ubp12 impairs the ability of yeast to cope with proteotoxic stress consistent with inefficient clearance of misfolded proteins by the ubiquitin/proteasome system. Our data suggest that ubiquitylation of Rad23 plays a stimulatory role in facilitating the transfer of ubiquitylated substrates to the proteasome.\n\nSummary statementUbiquitylation of a ubiquitin shuttle factor regulates the delivery of substrates at the proteasome, uncovering a novel regulatory link between ubiquitin and proteasomal degradation.

cell biology↗

bioRxiv2017

Structure of the archaellar motor and associated cytoplasmic cone in Thermococcus kodakaraensis

Archaeal swimming motility is driven by rotary motors called archaella. The structure of these motors, and particularly how they are anchored in the absence of a peptidoglycan cell wall, is unknown. Here, we use electron cryotomography to visualize the archaellar motor in vivo in Thermococcus kodakaraensis. Compared to the homologous bacterial type IV pilus (T4P), we observe structural similarities as well as several unique features. While the position of the cytoplasmic ATPase appears conserved, it is not braced by linkages that extend upward through the cell envelope as in the T4P, but rather by cytoplasmic components that attach it to a large conical frustum up to 500 nm in diameter at its base. In addition to anchoring the lophotrichous bundle of archaella, the conical frustum associates with chemosensory arrays and ribosome-excluding material and may function as a polar organizing center for the coccoid cells.

cell biology↗

bioRxiv2017

Knock down of Calcineurin-B2, a calcium binding regulatory subunit of Calcineurin, gives rise to hypercontraction myopathy in indirect flight muscles of Drosophila through dysregulation of calcium homeostasis

Abstract/SummaryMuscle is a calcium responsive tissue and requires calcium for initiation of muscle contraction. Calcium concentration in muscle is tightly regulated by calcium binding proteins. Calcineurin-B2 (canB2), a calcium binding, regulatory subunit of calcineurin, is the isoform maximally expressed in the indirect flight muscles (IFMs) of Drosophila. The developmental and functional roles of CanB2 particularly in the maintenance of calcium homeostasis are not understood. In this study, we show that the loss of canB2 causes hypercontraction of IFMs. Genetic interaction studies with hypercontraction mutants suggest a synergistic interaction between Calcineurin-B2 and structural protein Troponin-T. Similarly, interaction studies with dSERCA mutant reveal that Calcineurin-B2 is important for regulating calcium homeostasis in muscles. In vivo calcium imaging showed that Calcineurin-B2 deficiency leads to arrhythmicity in the calcium oscillations. We show that Calcineurin-B2 knockdown causes deregulation of calcium homeostasis, which results in unregulated acto-myosin interaction. However, overexpression of Calcineurin-A, which inhibits calcium oscillations, had no effect on myofibrillogenesis suggesting that calcium activation is dispensable for myofibrillar assembly. Our findings contribute to the understanding of muscle physiology in normal as well as pathophysiological conditions.

cell biology↗

bioRxiv2017

A novel mitochondrial enriched antioxidant protects neurons against acute oxidative stress

Excessive reactive oxygen species (ROS) can damage proteins, lipids, and DNA, which result in cell damage and death. The outcomes can be acute, as seen in stroke, or more chronic as observed in age-related diseases such as Parkinsons disease. Here we investigate the antioxidant ability of a novel synthetic flavonoid, Proxison (7-decyl-3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4-chromenone), using a range of in vitro and in vivo approaches. We show that, while it has radical scavenging ability on par with other flavonoids in a cell-free system, Proxison is orders of magnitude more potent than natural flavonoids at protecting neural cells against oxidative stress and is capable of rescuing damaged cells. The unique combination of a lipophilic hydrocarbon tail with a modified polyphenolic head group promotes efficient cellular uptake and mitochondrial localisation of Proxison. Importantly, in vivo administration of Proxison demonstrated effective and well tolerated neuroprotection against oxidative stress in a zebrafish model of dopaminergic neuronal loss.

cell biology↗

bioRxiv2017

NIMA-related kinase 1 (NEK1) regulates the localization and phosphorylation of α-Adducin (ADD1) and Myosin X (MYO10) during meiosis

Summary statementNEK1 kinase regulates the assembly and function of the meiosis I spindle by phosphorylating -adducin (ADD1) and thereby facilitating its interaction with Myosin X (MYO10)\n\nAbstractNIMA-related kinase 1 (NEK1) is a serine/threonine and tyrosine kinase that is highly expressed in mammalian germ cells. Mutations in Nek1 induce anemia, polycystic kidney and infertility. In this study we evaluated the role of NEK1 in meiotic spindle formation in both male and female gametes. Our results show that the lack of NEK1 provokes an abnormal organization of the meiosis I spindle characterized by elongated and/or multipolar spindles, and abnormal chromosome congression. The aberrant spindle structure is concomitant with the disruption in localization and protein levels of myosin X (MYO10) and -adducin (ADD1), both of which are implicated in the regulation of spindle formation during mitosis. Interaction of ADD1 with MYO10 is dependent on phosphorylation, whereby phosphorylation of ADD1 enables its binding to MYO10 on mitotic spindles. Reduction in ADD1 protein in NEK1 mutant mice is associated with hyperphosphorylation of ADD1, thereby preventing the interaction with MYO10 during meiotic spindle formation. Our results reveal a novel regulatory role for NEK1 in the regulation of spindle architecture and function during meiosis.

cell biology↗

bioRxiv2017

MiR-126 impairs the intestinal barrier function via inhibiting S1PR2 mediated activation of PI3K/AKT signaling pathway

BackgroundAberrant expression of miRNAs was a critical element in the pathogenesis of inflammatory bowel disease (IBD). This study aimed to explore the involvement and mechanism of miR-126 in IBD.\n\nMethodsIn this study, the endogenous expressions of miR-126, S1PR2 and S1P in the pathological tissues of patients with IBD were detected using qRT-PCR and western blot assay, respectively. The luciferase reporter gene assay was performed to confirm the targeting regulatory relation between miR-126 and S1PR2. The transendothelial electrical resistance assay was used to measured the value of TEER.\n\nResultsThe expressions of miR-126, S1PR2 and S1P in the pathological tissues of IBD patients were significantly higher than that of the control group. Moreover, miR-126 overexpression contributed to intestinal mucosal barrier dysfunction in vitro. S1PR2 was a direct target of miR-126, and S1PR2 expression was negatively regulated by miR-126 in Caco-2 cells. However, S1PR2 activated by S1P had the protection effect for the integrity and permeability of intestinal mucosal barrier via a PI3K/Akt dependent mechanism. MiR-126 silencing possessed obvious protective effects on the intestinal barrier function, but these effects could be reversed by JTE-013 or LY294002.\n\nConclusionMiR-126 down-regulated S1PR2 and then prevented the activation of PI3K/AKT signaling pathway, which ultimately could damage intestinal mucosal barrier function.

cell biology↗

bioRxiv2017

COPII-coated membranes function as transport carriers of intracellular procollagen-1

The coat protein complex II (COPII) is essential for the secretion of large cargo, such as the 300 nm precursor fibrils of procollagen I (PC1). Previous work has shown that the CUL3-KLHL12 complex increases the size of COPII vesicles to over 300 nm in diameter and accelerates the secretion of PC1; however, the role of large COPII vesicles as PC1 transport carriers was not unambiguously demonstrated. In this study, using stochastic optical reconstruction microscopy (STORM), correlated light electron microscopy (CLEM), and live cell imaging we report the existence of mobile COPII-coated vesicles that completely encapsulate the cargo PC1 and are physically separated from ER. We have also developed a cell-free COPII vesicle budding reaction that reconstitutes the capture of PC1 into large COPII vesicles. This process requires COPII proteins and the GTPase activity of the COPII subunit SAR1. We conclude from in vivo and in vitro evidence that large COPII vesicles are bona fide carriers of PC1.\n\nSummaryCOPII may play a direct or indirect role in the traffic of large protein complexes such as procollagen. Using high resolution imaging techniques in intact cells and in vitro reconstituted vesicles, Gorur et al. show that COPII coated vesicles carry procollagen1.

cell biology↗

bioRxiv2017

Anoxia-Induced VEGF-Release from Rat Cardiomyocites Promotes VascularDifferentiation of Human Mesenchymal Stem Cells.

BackgroundAlbeit several studies show that cellular therapy with bone marrow mesenchymal stem cells (BM-hMSCs) improves cardiac function after myocardial infarction (MI), the underlying mechanism is subject of controversy. Here we hypothesized that soluble factors, including VEGF, secreted by cardiomyocytes and BM-hMSCs under a low oxygen environment promote vascular differentiation of BM-hMSCs.\n\nMethodsHuman BM-MSCs were isolated and expanded in vitro by the same procedure we employed to prepare cells suitable for cardiac cell therapy. BM-hMSCs were characterized by flow cytometry and functional analysis. Vascular differentiation was induced by VEGF or by conditioned media from neonate rat ventricular cardiomyocytes (NRVCs) cultured in anoxia and confirmed by immunostaining, tube formation over matrigel and cell migration across transwells. Presence of VEGF in conditioned media was determined by ELISA and activation of VEGF signaling by Western blot.\n\nResultsBM-hMSCs used in this study met the criteria recommended by International Society for Cellular Therapy for defining mesenchymal stromal cells. Von Willebrand factor (vWF) expression and tube formation in matrigel indicate that these cells had the capacity to differentiate into the endothelial lineage, which was further enhanced by VEGF and conditioned media from NRVCs cultured in anoxia. Furthermore, condition media and VEGF stimulated cell migration across transwells, which demonstrates the migratory capacity of BM-hMSCs. Finally, when VEGF signaling was blocked by neutralizing anti-VEGF, vascular differentiation of BM-hMSCs was reduced to basal levels.\n\nConclusionsSoluble VEGF released in the culture media after exposure to low oxygen conditions is responsible for endothelial differentiation of BM-hMSCs.

cell biology↗

bioRxiv2017

PBAF’s genomic binding dynamics are regulated via bromodomain-acetyl-lysine interactions and select chromatin states

Transcriptional bursting involves genes rapidly switching between active and inactive states. Chromatin remodelers actively target arrays of acetylated nucleosomes at select enhancers and promoters to facilitate or shut down the repeated recruitment of RNA Pol II during transcriptional bursting. It is unknown how acetylated chromatin is dynamically targeted and regulated by chromatin remodelers such as PBAF. Thus, we sought to understand how PBAF targets acetylated chromatin using live-cell single molecule fluorescence microscopy. Our work reveals chromatin hubs throughout the nucleus where PBAF rapidly cycles on and off the genome. Deletion of PBAFs bromodomains impairs targeting, stable engagement and persistent binding on chromatin in hubs. Interestingly, PBAF has a higher probability to stably engage chromatin inside hubs indicating that hubs contain a unique nucleosomal scaffold compared to global chromatin. Dual color imaging of PBAF in hubs near H3.3 or HP1 reveals that PBAF targets both euchromatic and heterochromatic regions with distinct genome binding kinetics that mimic chromatin stability. Removal of PBAFs bromodomains stabilizes H3.3 and HP1 binding within chromatin indicating that bromodomains may play a direct role in remodeling of the nucleosome. Our data, suggests that PBAF differentially and dynamically engages a variety of chromatin structures involved in both activation and repression of transcription via bromodomains. Furthermore, PBAFs binding stability on chromatin may reflect the chromatin remodeling potential of different bound chromatin states. Statement of SignificanceTranscriptional bursting involves a gene rapidly switching between transcriptionally active and inactive states. To regulate transcriptional bursting, chromatin must interchange between euchromatin and heterochromatin to permit or restrict access of transcription factors including RNA Polymerase II to enhancer and gene promoters. However, little is known regarding how chromatin remodelers dynamically read a rapidly changing 4D epigenome. We used live-cell single molecule imaging to characterize the spatiotemporal chromatin binding dynamics of PBAF, a chromatin remodeler that accesses both euchromatin and heterochromatin to regulate transcription. PBAF cycles on and off chromatin hubs in select nuclear regions where it distinctly engages euchromatin and heterochromatin via bromodomains in its BAF180 subunit. Our study provides the framework to understand how the 4D epigenome is regulated.

cell biology↗

bioRxiv2017

dMARCH8, a Drosophila ubiquitin ligase, regulates polymodifications of tubulin in the spermiogenic pathway

Ciliary stability and function are regulated by the covalent addition of polyglutamate and polyglycine chains to axonemal tubulin subunits. The Drosophila gene CG13442 encodes a predicted ubiquitin E3 ligase involved in the regulation of tubulin glycylation and glutamylation. Homologous to mammalian MARCH8, CG13442/dMARCH8 is required for male fertility. Sperm in dMARCH8 mutant testes appear to undergo a normal individualization process but fail to be transferred to the seminal vesicle. This phenotype is very similar to that of mutants in the Ntl gene, shown here to be a glycine transporter using a [3H]glycine uptake assay. Mutations in dMARCH8 are associated with a reduction of both polyglutamylation and polyglycylation of sperm tubulin. Polyglutamylation of tubulin is significantly increased in the Ntl- background, and recovers to wild-type levels in the Ntl--dMARCH8- double mutant background, indicating that glycine and glutamate compete for some common site(s) on tubulin molecules in this system. By analogy to the regulation of the mammalian glycine transporter GlyT2 through ubiquitin-mediated trafficking between the plasma membrane and endosome, dMARCH8 may target Ntl and glutamate transporters, or other upstream regulators of these proteins.

cell biology↗

bioRxiv2017

Super-resolution microscopy reveals the three-dimensional organization of meiotic chromosome axes in intact C. elegans tissue

When cells enter meiosis, their chromosomes reorganize as linear arrays of chromatin loops anchored to a central axis. Meiotic chromosome axes form a platform for the assembly of the synaptonemal complex (SC), and play central roles in other meiotic processes, including homologous pairing, recombination, and chromosome segregation. However, little is known about the three-dimensional organization of components within the axes, which consist of cohesin complexes and additional meiosis-specific proteins. Here we investigate the molecular organization of meiotic chromosome axes in C. elegans through STORM and PALM superresolution imaging of intact germline tissue. By tagging one axis protein (HIM-3) with a photoconvertible fluorescent protein, we established a spatial reference for other components, which were localized using antibodies against epitope tags inserted by CRISPR/Cas9 genome editing. Using three-dimensional averaging, we determined the 3D-organization of all known components within synapsed chromosome axes to a precision of 2-5 nanometers. We find that meiosis-specific HORMA-domain proteins span a gap between cohesin complexes and the central region of the SC, consistent with their essential roles in SC assembly. Our data further suggest that the two different meiotic cohesin complexes are distinctly arranged within the axes: Cohesin complexes containing COH-3 or -4 kleisins form a central core in the central plane of the axes, whereas complexes containing REC-8 kleisin protrude above and below the plane defined by the SC. This splayed organization may help to explain the role of the chromosome axes in promoting inter-homolog repair of meiotic double strand breaks by inhibiting inter-sister repair.

cell biology↗

bioRxiv2017

DHX15 regulates CMTR1-dependent gene expression and cell proliferation

CMTR1 contributes to mRNA cap formation by methylating the O-2 position of the 1st transcribed nucleotide ribose. mRNA cap O-2 methylation has roles in mRNA translation and self-RNA tolerance in innate immunity, however its role in cell physiology is unclear. We report that CMTR1 is recruited to Serine-5 phosphorylated RNA Pol II CTD, facilitating cotranscriptional methylation. We isolated CMTR1 in a complex with DHX15, an RNA helicase functioning in splicing and ribosome biogenesis, and characterised it as a regulator of CMTR1. When bound to DHX15, CMTR1 activity is repressed and prevented from binding to RNA pol II, thus constraining 1st nucleotide methylation to a co-transcriptional event. Conversely CMTR1 activates DHX15 helicase activity and influences its nuclear localisation, which is likely to impact on several nuclear functions. The impact of the CMTR1-DHX15 interaction is complex and will depend on the relative expression of these enzymes and their interactors, and the cellular dependency on different RNA processing pathways. In HCC1806 cells, the DHX15-CMTR1 interaction controls ribosome loading of a subset of mRNAs and impacts on cell proliferation.

cell biology↗

bioRxiv2017

Cartilage microRNA dysregulation during the onset and progression of mouse osteoarthritis overlaps with patient disease candidates

To explore the role of microRNAs in osteoarthritis (OA), we conducted microRNA expression profiling on micro-dissected tibial cartilage and subchondral bone in a mouse model of OA produced by medial meniscus destabilization (DMM). DMM mice had characteristic cartilage degeneration, subchondral bone sclerosis and osteophyte formation. While subchondral bone showed no microRNA dysregulation, 139 microRNAs were differentially expressed in DMM cartilage at 1 and/or 6 weeks after OA initiation. To prioritize OA-candidates, dysregulated microRNAs with human orthologues were filtered using paired microRNA:mRNA expression analysis to identify those with corresponding changes in mRNA target transcripts in the DMM cartilage. An important cohort overlapped with microRNAs identified in human end-stage OA. Comparisons with microRNAs dysregulation in DMM mouse cartilage where aggrecan cleavage was genetically-ablated demonstrated that all were independent of aggrecan breakdown, earmarking these as important to the critical stages of OA initiation. Our comprehensive analyses identified high-priority microRNA candidates that have potential as human OA-biomarkers and therapeutic targets.\n\nSUMMARYKung et al. conducted global analysis of microRNA dysregulation in joint tissues of a well-established mouse osteoarthritis model. Stringent filtering against human microRNA orthologues, integrated mRNA target analysis and comparison with published studies on human end-stage osteoarthritis identified microRNA candidates of potential clinical relevance.

cell biology↗

bioRxiv2017

Cell cycle entry triggers a switch between two modes of Cdc42 activation during yeast polarization

Cell polarization underlies many cellular and organismal functions. The GTPase Cdc42 orchestrates polarization in many contexts. In budding yeast, polarization is associated with a focus of Cdc42*GTP which is thought to self sustain by recruiting a complex containing Cla4, a Cdc42-binding effector, Bem1, a scaffold and Cdc24, a Cdc42 GEF. Using optogenetics, we probe yeast polarization and find that local recruitment of Cdc24 or Bem1 is sufficient to induce polarization by triggering self-sustaining Cdc42 activity. However, the response to these perturbations depends on the recruited molecule, the cell cycle stage, and existing polarization sites. Before cell cycle entry, recruitment of Cdc24, but not Bem1, induces a metastable pool of Cdc42 that is sustained by positive feedback. Upon Cdk1 activation, recruitment of either Cdc24 or Bem1 creates a stable site of polarization that induces budding and inhibits formation of competing sites. Local perturbations have therefore revealed unexpected features of polarity establishment.

cell biology↗

bioRxiv2017

ES cell derived neural progenitors improves visual functions in retinal ganglion cells - depleted mouse models

Retinal ganglion cells (RGC) transplantation is a promising strategy to restore visual function resulting from irreversible RGC degeneration occurring in glaucoma or inherited optic neuropathies. We previously demonstrated FGF2 induced differentiation of mouse embryonic stem cells (ESC) to RGC lineage, capable of retinal Ganglion Cell Layer (GCL) integration upon transplantation in mice. Here, we evaluated possible improvement of visual function by transplantation of ES cell derived neural progenitors in RGC depleted glaucoma mice models. ESC derived neural progenitors (ES-NP) were transplanted into NMDA (N-Methyl-D-Aspartate) injected, RGC-ablated mouse models and a pre-clinical glaucoma mouse model (DBA/2J) having sustained higher intra ocular pressure (IOP). Visual acuity and functional integration was evaluated by behavioural experiments and immunohistochemistry, respectively. GFP-expressing ES-NPs transplanted in NMDA-injected RGC-depleted mice differentiated into RGC lineage and possibly integrating into GCL. An improvement in visual acuity was observed after two months of transplantation, when compared to the pre-transplantation values. Expression of c-Fos in the transplanted cells, upon light induction, further suggests functional integration into the host retinal circuitry. However, the transplanted cells did not send axonal projections into optic nerve. Transplantation experiments in DBA/2J mouse showed no significant improvement in visual functions, possibly due to both host and transplanted retinal cell death which could be due to an inherent high IOP. We showed that, transplantation of ES-NPs into the retina of RGC-ablated mouse models could survive, differentiate to RGC lineage, and possibly integrate into GCL to improve visual function. However, for the survival of transplanted cells in glaucoma, strategies to control the IOP are warranted.

cell biology↗