Biology subjects

Zhuo, Y.

Publications and source records attributed to Zhuo, Y..

24 records · Page 2Linked to original sources

bioRxiv2020

Subcortical magnocellular visual system facilities object recognition by processing topological property

The Magnocellular (M) visual pathway is known as a fast route to convey coarse information and facilitates object recognition by initiating top-down processes. It is unclear what exact properties M pathway conveys to accelerate visual object processing. Previous studies suggest that visual systems are highly sensitive to the perception of topological property (TP), which remains unchanged under various shape changes, and the TP is probably processed through a fast subcortical pathway. Here we hypothesize that a subcortical M system contributes to the fast object recognition by processing TP first. We first demonstrate that the facilitation effect of TP processing on object perception occurs mainly in the M visual system, and then support the subcortical M hypothesis of TP processing by the evidence that the early processing of TP was not affected when cortical function was temporarily damaged by the transcranial magnetic stimulation and when stimuli were biased to M system.

neuroscience↗

bioRxiv2019

Exponential Growth of Glioblastoma In Vivo Driven by Rapidly Dividing and Outwardly Migrating Cancer Stem Cells

How overall tumor growth emerges from the properties of functionally heterogeneous tumor cell subpopulations is a fundamental question of cancer biology. Here we combined lineage tracing, continuous monitoring of tumor mass, proliferation assays and transcriptomics with mathematical modeling and statistical inference to dissect the growth of glioblastoma in mice. We found that tumors grow exponentially at the rate of symmetric divisions of brain tumor stem cells (BTSCs). Spatial modeling predicts, and data show, that BTSCs accumulate at the tumor rim rather than in the core. The physiological differentiation hierarchy downstream of BTSCs is preserved in mice and humans: transit amplifying progenitors give rise to terminally differentiated cells. Consistent with our quantification of the mechanisms underlying tumor growth, molecular data show elevated expression of cell cycle-and migration-related genes in BTSCs. Our systematic approach reveals fundamental properties of glioblastoma and may be transferable to the study of other animal models of cancer.

cancer biology↗

bioRxiv2019

Potential role of heat shock protein 90 in regulation of hyperthermia-driven differentiation of neural stem cells

ObjectiveOur previous studies indicated that hyperthermia may play a role in differentiation of neural stem cells and that hypoxia inducible factor-1(HIF-1) was critical in this process. Heat shock protein 90 (Hsp90) is one of the most common heat-related proteins and involved in HIF-1 expression by regulating its activity and stabilization. Here, we hypothesized that HSP90 may be involved in regulation of hyperthermia-driven differentiation of neural stem cells(NSCs). We also investigated whether the HSP90 activity exert its regulatory action via HIF-1 pathway and the transcriptional level of the target genes of HIF-1.\n\nMethodThe cultured NSCs were divided into three groups: an hyperthermic treatment group(40NSC) which NSCs was induced under 40{degrees}C temperature; a control group(37NSC) which NSCs was induced under 37{degrees}C temperature; an hyperthermic treatment and HSP90-inhibited group(40NSC+GA) which NSCs was induced with 0.5M HSP90 inhibitor Geldanamycin(GA) under 40{degrees}C temperature. We examined cells HSPa and HIF-1a expression during a time window of 5 days(12h, 1d, 3d, 5d) post-differentiation. The expression HSP, HIF-1, VEGF (vascular endothelial growth factor) and erythmpoietin(EPO) of during a time window was evaluated by RT-qPCR. The proportion of Tuj-1 positive differentiated cells were observed by flow cytometry.\n\nResultHyperthermia promoted neuronal differentiation of NSC, and this effect could be blocked by HSP90 inhibitor GA. We observed the up-regulation of HSP90 during hyperthermia treatment, and that the protein levels of HIF-1 changed depending of the GA treatment. GA could not inhibited HSP90 expression but suppressed HSP activity and decreased the expression HIF-1 protein. Inhibition of HIF-1 expression by GA could consequently affect expression of its targeted genes such as VEGF and EPO.\n\nConclusionHyperthermia promote differentiation of NSCs into neurons. HSP90 involved in the regulation of hyperthermia-driven differentiation of NSC, and the mechanism is related to HIF-1 and its downstream gene activation.

cell biology↗

bioRxiv2019

Extensive adaptive immune response of AAVs and Cas proteins in non-human primates

The CRISPR-mediated Cas system is the most widely used tool in gene editing and gene therapy for its convenience and efficiency. Delivery of the CRISPR system by adeno-associated viruses (AAVs) is currently the most promising approach to gene therapy. However, pre-existing adaptive immune responses against CRISPR nuclease (PAIR-C) and AAVs has been found in human serum, indicating that immune response is a problem that cannot be ignored, especially for in vivo gene correction. Non-human primates (NHPs) share many genetic and physiological traits with human, and are considered as the bridge for translational medicine. However, whether NHPs have same PAIR-C status with human is still unknown. Here, macaques (rhesus and cynomolgus), including normal housed and CRISPR-SpCas9 or TALENs edited individuals, were used to detect PAIR-C which covered SaCas9, SpCas9, AsCas12a and LbCas12a. Dogs and mice were also detected to expand the range of species. In addition, pre-existing adaptive antibodies to AAV8 and AAV9 were performed against macaques of different ages. The results showed that adaptive immunity was pre-existing in the macaques regardless of Cas proteins and AAVs. These findings indicate that the pre-existing adaptive immune of AAV-delivered CRISPR construction and correction system should be concerned for in vivo experiments.

immunology↗

bioRxiv2018

Single-cell RNA-seq analysis maps the development of human fetal retina

Vision starts with image formation at the retina, which contains diverse neuronal cell types that extract, process, and relay visual information to higher order processing centers in the brain. Though there has been steady progress in defining retinal cell types, very little is known about retinal development in humans, which starts well before birth. In this study, we performed transcriptomic profiling of developing human fetal retina from gestational weeks 12 to 27 using single-cell RNA-seq (scRNA-seq) and used pseudotime analysis to reconstruct the developmental trajectories of retinogenesis. Our analysis reveals transcriptional programs driving differentiation down four different cell types and suggests that Muller glia (MG) can serve as embryonic progenitors in early retinal development. In addition, we also show that transcriptional differences separate retinal progenitor cells (RPCs) into distinct subtypes and use this information to reconstruct RPC developmental trajectories and cell fate. Our results support a hierarchical program of differentiation governing cell-type diversity in the developing human retina. In summary, our work details comprehensive molecular classification of retinal cells, reconstructs their relationships, and paves the way for future mechanistic studies on the impact of gene regulation upon human retinogenesis.

neuroscience↗

bioRxiv2017

Autonomous Combinatorial Color Barcoding For Multiplexing Single Molecule RNA Visualization

Single molecular fluorescence in situ hybridization (smFISH) detects RNA transcripts with spatial information and digital molecular counting. However, the broad usage of smFISH is still hindered by the complex chemical probe conjugation or microscopy set-up, especially for investigating multiple gene expression. Here we present a multiple fluorophore enzymatic labeling method (termed HuluFISH) for smFISH probes to achieve flexible combinatorial color barcoding in single hybridization step. The multiplex capacity of HuluFISH follows an exponential growth with the increase of the number of fluorophore types. We demonstrate that this method can be used to detect cellular heterogeneity in embryonic mouse brain on single cell level.

molecular biology↗