Biology subjects

Chen, X.

Publications and source records attributed to Chen, X..

At least 937 records · Page 52Linked to original sources

bioRxiv2022

BDNF and TRiC-inspired Reagents Rescue Cortical Synaptic Deficits in a Mouse Model of Huntington's Disease

Huntingtons disease (HD) results from a CAG repeat expansion in the gene for Huntington (HTT) resulting in expansion of the polyglutamine (Q) tract in the mutant protein (mHTT). Synaptic changes are early manifestations of neuronal dysfunction in HD. However, the mechanism(s) by which mHTT impacts synapse formation and function is not well defined. Herein we explored HD pathogenesis in the BACHD and the {Delta}N17-BACHD mouse models of HD by examining cortical synapse formation and function in primary cultures maintained for up to 35 days (DIV35). We identified synapses by immunostaining with antibodies against pre-synaptic (Synapsin 1) and a post-synaptic (PSD95) marker. Consistent with earlier studies, cortical neurons from both WT and the HD models began to form synapses at DIV14; at this age there were no genotypic differences in synapse numbers. However, from DIV21 through DIV35 BACHD neurons showed progressively smaller numbers of synapses relative to WT neurons. Remarkably, BACHD synaptic deficits were completely rescued by treating cultures with BDNF. Building on earlier studies using reagents inspired by the chaperonin TRiC, we found that addition of the recombinant apical domain of CCT1 partially rescued synapse number. Unexpectedly, unlike BACHD cultures, synapses in {Delta}N17-BACHD cultures showed a progressive increase in number as compared to WT neurons, thus distinguishing synaptic changes in these HD models. Using multielectrode arrays, we discovered age-related functional deficits in BACHD cortical cultures with significant differences present by DIV28. As for synapse number, BDNF treatment prevented most synaptic deficits, including mean firing rate, spikes per burst, inter-burst interval, and synchrony. The apical domain of CCT1 showed similar, albeit less potent effects. These data are evidence that deficits in HD synapse number and function can be replicated in vitro and that treatment with either BDNF or a TRiC-inspired reagent can prevent them. Our findings support the use of cellular models to further explicate HD pathogenesis and its treatments.

neuroscience↗

bioRxiv2022

Starfysh reveals heterogeneous spatial dynamics in the breast tumor microenvironment

Spatially-resolved gene expression profiling provides valuable insight into tissue organization and cell-cell crosstalk; however, spatial transcriptomics (ST) lacks single-cell resolution. Current ST analysis methods require single-cell RNA sequencing data as a reference for a rigorous interpretation of cell states and do not utilize associated histology images. Significant sample variation further complicates the integration of ST datasets, which is essential for identifying commonalities across tissues or altered cellular wiring in disease. Here, we present Starfysh, the first comprehensive computational toolbox for joint modeling of ST and histology data, dissection of refined cell states, and systematic integration of multiple ST datasets from complex tissues. Starfysh uses an auxiliary deep generative model that incorporates archetypal analysis and any known cell state markers to avoid the need for a single-cell-resolution reference in characterizing known or novel tissue-specific cell states. Additionally, Starfysh improves the characterization of spatial dynamics in complex tissues by leveraging histology images and enables the comparison of niches as spatial "hubs" across tissues. Integrative analysis of primary estrogen receptor-positive (ER+) breast cancer, triple-negative breast cancer (TNBC), and metaplastic breast cancer (MBC) tumors using Starfysh led to the identification of heterogeneous patient- and disease-specific hubs as well as a shared stromal hub with varying spatial orientation. Our results show the ability to delineate the spatial co-evolution of tumor and immune cell states and their crosstalk underlying intratumoral heterogeneity in TNBC and revealed metabolic reprogramming shaping immunosuppressive hubs in aggressive MBC. Starfysh is publicly available (https://github.com/azizilab/starfysh).

bioinformatics↗

bioRxiv2022

Spatial transcriptomics of T and B cell receptors uncovers lymphocyte clonal dynamics in human tissue.

The spatial distribution of lymphocyte clones within tissues is critical to their development, selection, and expansion. We have developed Spatial Transcriptomics of VDJ sequences (Spatial VDJ), which maps immunoglobulin and TR antigen receptors in human tissue sections. Spatial VDJ captures lymphocyte clones matching canonical T, B, and plasma cell distributions in tissues and amplifies clonal sequences confirmed by orthogonal methods. We confirm spatial congruency between paired receptor chains, develop a computational framework to predict receptor pairs, and link the expansion of distinct B cell clones to different tumor-associated gene expression programs. Spatial VDJ delineates B cell clonal diversity, class switch recombination, and lineage trajectories within their spatial context. Taken together, Spatial VDJ captures lymphocyte spatial clonal architecture across tissues, which could have important therapeutic implications. One-Sentence SummarySpatial transcriptomics-based technology co-captures T and B cell receptors within their anatomical niche in human tissue.

immunology↗

bioRxiv2022

Reconstructing the formation of Hmong-Mien genetic fine-structure

The linguistic, historical, and subsistent uniqueness of Hmong-Mien (HM) speakers offers a wonderful opportunity to investigate how these factors impact the genetic structure. Nevertheless, the genetic differentiation among HM-speaking populations and the formation process behind are far from well characterized in previous studies. Here, we generated genome-wide data from 67 Yao ethnicity samples and analyzed them together with published data, particularly by leveraging haplotype-based methods. We identify that the fine-scale genetic substructure of HM-speaking populations corresponds better to linguistic classification than to geography, while the parallel of serial founder events and language differentiations can be found in West Hmongic speakers. Multiple lines of evidence indicate that ~500-year-old GaoHuaHua individuals are most closely related to West Hmongic-speaking Bunu. The excessive level of the genetic bottleneck of HM speakers, especially Bunu, is in agreement with their long-term practice of slash-and-burn agriculture. The inferred admixture dates in most of the HM-speaking populations overlap the reign of the Ming dynasty (1368 - 1644 CE). Besides the common genetic origin of HM speakers, their external ancestry majorly comes from neighboring Han Chinese and Kra-Dai speakers in South China. Conclusively, our analysis reveals the recent isolation and admixture events that contribute to the fine-scale genetic formation of present-day HM-speaking populations underrepresented in previous studies.

genomics↗

bioRxiv2022

Feedback brings scene information to the representation of occluded image regions in area V1 of monkeys and humans

Neuronal activity in the primary visual cortex (V1) is driven by feedforward input from within the neurons receptive fields (RFs) and modulated by contextual information in regions surrounding the RF. The effect of contextual information on spiking activity occurs rapidly, and is therefore challenging to dissociate from feedforward input. To address this challenge, we recorded the spiking activity of V1 neurons in monkeys viewing either natural scenes or scenes where the information in the RF was occluded, effectively removing the feedforward input. We found that V1 neurons responded rapidly and selectively to occluded scenes. V1 responses elicited by occluded stimuli could be used to decode scene identity and could be predicted from those elicited by non-occluded images, indicating that there is overlap between visually-driven and contextual responses. We used representational similarity analysis to show that the structure of V1 representations of occluded scenes measured with electrophysiology in monkeys correlates strongly with the representations of the same scenes in humans measured with fMRI. Our results reveal that contextual influences alter the spiking activity of V1 in monkeys across large distances on a rapid time scale, carry information about scene identity and resemble those in human V1.

neuroscience↗

bioRxiv2022

Cholecystokinin from the Rhinal Cortex Facilitates Motor Skill Learning

Cholecystokinin (CCK) is an essential modulator for neuroplasticity in sensory and emotional domains. Here, we investigated the role of CCK in motor learning using a single pellet reaching task in mice. Mice with a knockout of cck gene (CCK-/-) or blockade of CCK-B receptor (CCKBR) showed defective motor learning ability; the success rate of retrieving reward remained at the baseline level compared to the wildtype mice with significantly increased success rate. We observed no long-term potentiation (LTP) upon high-frequency stimulation (HFS) in the motor cortex of CCK-/- mice, indicating a possible association between motor learning deficiency and neuronal plasticity in the motor cortex. In vivo calcium imaging demonstrated that the deficiency of CCK signalling disrupted the refinement of population neuronal activity in the motor cortex during motor skill training. Anatomical tracing revealed direct projections from CCK-expressing neurons in the rhinal cortex to the motor cortex. Inactivating the CCK neurons in the rhinal cortex using chemogenetic methods significantly suppressed motor learning, and intraperitoneal application of CCK4, a tetrapeptide CCK agonist, rescued the motor learning deficits of CCK-/- mice. In summary, our results suggest that CCK, which could be provided from the rhinal cortex, enables neuroplasticity in the motor cortex leading to motor skill learning.

neuroscience↗

bioRxiv2022

Coupling of perinuclear actin cap and nuclear mechanics regulates flow-induced YAP spatiotemporal nucleocytoplasmic transport

Mechanical forces, including flow shear stress, regulate fundamental cellular process by modulating the nucleocytoplasmic transport of transcription factors, such as Yes-associated Protein (YAP). However, the mechanical mechanism how flow induces the nucleocytoplasmic transport remains largely unclear. Here we found that unidirectional flow applied to endothelial cells induces biphasic YAP nucleocytoplasmic transport with initial nuclear import, followed by nuclear export as perinuclear actin cap forms and nuclear stiffening in a dose and timing-dependent manner. In contrast, pathological oscillatory flow induces slight actin cap formation and nuclear softening, sustaining YAP nuclear localization. To explain the disparately spatiotemporal distribution of YAP, we developed a three-dimensional mechanochemical model considering coupling processes of flow sensing, cytoskeleton organization, nucleus mechanotransduction, and YAP spatiotemporal transport. We discovered that actin cap formation and nuclear stiffness alteration under flow synergically regulate nuclear deformation, hence governing YAP transport. Furthermore, we expanded our single cell model to a collective vertex framework and found that actin cap irregularities in individual cells under flow shear stress potentially induce topological defects and spatially heterogeneous YAP distribution in cellular monolayers. Our work unveils the unified mechanism of flow-induced nucleocytoplasmic transport, offering a universal linkage between transcriptional regulation and mechanical stimulation.

bioengineering↗

bioRxiv2022

Comparative Mucomic Analysis of Three Functionally Distinct Cornu aspersum Secretions

Every animal secretes mucus, placing them among the most diverse biological materials. Mucus hydrogels are complex mixtures of water, ions, carbohydrates, and proteins. Uncertainty surrounding their composition and how interactions between components contribute to mucus function complicates efforts to exploit their properties. There is substantial interest in commercializing mucus from the garden snail, Cornu aspersum, for skincare, drug delivery, tissue engineering, and composite materials. C. asperum secretes three mucus -- one shielding the animal from environmental threats, one adhesive mucus from the pedal surface of the foot, and another pedal mucus that is lubricating. It remains a mystery how compositional differences account for their substantially different properties. Here, we characterize mucus proteins, glycosylation, ion content, and mechanical properties to understand structure-function relationships through an integrative "mucomics" approach. We identify new macromolecular components of these hydrogels, including a novel protein class termed Conserved Anterior Mollusk Proteins (CAMPs). Revealing differences between C. aspersum mucus shows how considering structure at all levels can inform the design of mucus-inspired materials.

biochemistry↗

bioRxiv2022

PAST: latent feature extraction with a Prior-based self-Attention framework for Spatial Transcriptomics

Rapid advances in spatial transcriptomics (ST) have revolutionized the interrogation of spatial heterogeneity and increased the demand for comprehensive methods to effectively characterize spatial domains. As a prerequisite for ST data analysis, spatial domain characterization is a crucial step for downstream analyses and biological implications. Here we propose PAST, a variational graph convolutional auto-encoder for ST, which effectively integrates prior information via a Bayesian neural network, captures spatial patterns via a self-attention mechanism, and enables scalable application via a ripple walk sampler strategy. Through comprehensive experiments on datasets generated by different technologies, we demonstrated that PAST could effectively characterize spatial domains and facilitate various downstream analyses, including ST visualization, spatial trajectory inference and pseudo-time analysis, by integrating spatial information and reference from various sources. Besides, we also show the advantages of PAST for accurate annotation of spatial domains in newly sequenced ST data and biological implications in the annotated domains.

bioinformatics↗

bioRxiv2022

Prediction of Transport, Deposition, and Resultant Immune Response of Nasal Spray Vaccine Droplets using a CFPD-HCD Model in a 6-Year-Old Upper Airway Geometry to Potentially Prevent COVID-19

This study focuses on the transport, deposition, and triggered immune response of intranasal vaccine droplets to the Angiotensin-converting enzyme 2-rich region (i.e., the olfactory region (OR)) in the nasal cavity of a 6-year-old female to possibly prevent COVID-19. To investigate how administration strategy can influence nasal vaccine efficiency, a validated multiscale model (i.e., computational fluid-particle dynamics (CFPD) and host-cell dynamics (HCD) model) was employed. Droplet deposition fraction, size change, residence time, and the area percentage of OR covered by the vaccine droplets and triggered immune system response were predicted with different spray cone angles, initial droplet velocities, and compositions. Numerical results indicate that droplet initial velocity and composition have negligible influences on the vaccine delivery efficiency to OR. In contrast, the spray cone angle can significantly impact the vaccine delivery efficiency. The triggered immunity was not significantly influenced by the administration investigated in this study, due to the low percentage of OR area covered by the droplets. To enhance the effectiveness of the intranasal vaccine to prevent COVID-19 infection, it is necessary to optimize the vaccine formulation and administration strategy so that the vaccine droplets can cover more epithelial cells in OR to minimize the available receptors for SARS-CoV-2.

bioengineering↗

bioRxiv2022

Hydrodynamic and anthropogenic disturbances co-shape microbiota rhythmicity and community assembly within intertidal groundwater-surface water continuum

Tidal hydrodynamics drive the groundwater-seawater exchange and shifts in microbiota structure in the coastal zone. However, how the coastal water microbiota structure and assembly patterns respond to periodic tidal fluctuations and anthropogenic disturbance remain unexplored in the intertidal groundwater-surface water (GW-SW) continuum, although it affects biogeochemical cycles and coastal water quality therein. Here, through hourly time-series sampling in the saltmarsh tidal creek, rhythmic patterns of microbiota structure in response to daily and monthly tidal fluctuations in intertidal surface water are disentangled for the first time. The similarity in archaeal community structures between groundwater and ebb-tide surface water (R2=0.06, p=0.2) demonstrated archaeal transport through groundwater discharge, whereas multi-source transport mechanisms led to unique bacterial biota in ebb-tide water. Homogeneous selection (58.6%-69.3%) dominated microbiota assembly in the natural intertidal GW-SW continuum and the presence of 157 rhythmic ASVs identified at ebb tide and 141 at flood tide could be attributed to different environmental selection between groundwater and seawater. For intertidal groundwater in the tidal creek affected by anthropogenically contaminated riverine inputs, higher microbial diversity and shift in community structure were primarily controlled by increased co-contribution of dispersal limitation and drift (jointly 57.8%) and enhanced microbial interactions. Overall, this study fills the knowledge gaps in the tide-driven water microbial dynamics in coastal transition zone and the response of intertidal groundwater microbiota to anthropogenic pollution of overlying waters. It also highlights the potential of microbiome analysis in enhancing coastal water quality monitoring and identifying anthropogenic pollution sources (e.g., aquaculture pathogenic Vibrio) through the detection of rhythmic microbial variances associated with intertidal groundwater discharge and seawater intrusion.

ecology↗

bioRxiv2022

Modular cell type organization of cortical areas revealed by in situ sequencing

The cortex is composed of neuronal types with diverse gene expression that are organized into specialized cortical areas. These areas, each with characteristic cytoarchitecture (Brodmann 1909; Vogt and Vogt 1919; Von Bonin 1947), connectivity (Zingg et al. 2014; Harris et al. 2019), and neuronal activity (Schwarz et al. 2008; Ferrarini et al. 2009; He et al. 2009; Meunier et al. 2010; Bertolero et al. 2015), are wired into modular networks (Zingg et al. 2014; Harris et al. 2019; Huang et al. 2020). However, it remains unclear whether cortical areas and their modular organization can be similarly defined by their transcriptomic signatures and how such signatures are established in development. Here we used BARseq, a high-throughput in situ sequencing technique, to interrogate the expression of 104 cell type marker genes in 10.3 million cells, including 4,194,658 cortical neurons over nine mouse forebrain hemispheres at cellular resolution. De novo clustering of gene expression in single neurons revealed transcriptomic types that were consistent with previous single-cell RNAseq studies(Yao et al. 2021a; Yao et al. 2021b). Gene expression and the distribution of fine-grained cell types vary along the contours of cortical areas, and the composition of transcriptomic types are highly predictive of cortical area identity. Moreover, areas with similar compositions of transcriptomic types, which we defined as cortical modules, overlap with areas that are highly connected, suggesting that the same modular organization is reflected in both transcriptomic signatures and connectivity. To explore how the transcriptomic profiles of cortical neurons depend on development, we compared the cell type distributions after neonatal binocular enucleation. Strikingly, binocular enucleation caused the cell type compositional profiles of visual areas to shift towards neighboring areas within the same cortical module, suggesting that peripheral inputs sharpen the distinct transcriptomic identities of areas within cortical modules. Enabled by the high-throughput, low-cost, and reproducibility of BARseq, our study provides a proof-of-principle for using large-scale in situ sequencing to reveal brain-wide molecular architecture and to understand its development.

neuroscience↗

bioRxiv2022

PRMT5 links lipid metabolism to contractile function of skeletal muscles

The skeletal muscle plays a key role in systemic energy homeostasis besides its canonical contractile function, but what couples these functions is poorly defined. Protein Arginine MethylTransferase 5 (PRMT5) is a well-known oncoprotein but also expressed in healthy tissues with unclear physiological functions. As adult muscles express high levels of Prmt5, we generated myocyte-specific Prmt5 knockout (Prmt5MKO) mice. We observed reduced muscle mass, oxidative capacity, force production and exercise performance in Prmt5MKO mice. The motor deficiency is associated with scarce lipid droplets in myofibers due to defects in lipid biosynthesis and degradation. First, Prmt5MKO reduced demethylation and stability of Sterol Regulatory Element-Binding Transcription Factor 1a (SREBP1a), a master regulator of de novo lipogenesis. Second, Prmt5MKO impaired the repressive H4R3Me2s (histone H4 arginine-3 symmetric demethylation) at the Pnpla2 gene, elevating the level of its encoded protein ATGL, the rate-limiting enzyme catalyzing lipolysis. Accordingly, myocyte-specific double knockout of Pnpla2 and Prmt5 normalized muscle mass and function. Together, our findings delineate a physiological function of PRMT5 in linking lipid metabolism to contractile function of myofibers.

molecular biology↗

bioRxiv2022

Subcytoplasmic location of translation controls protein output

The cytoplasm is highly compartmentalized, but the extent and consequences of subcytopIasmic mRNA localization in non-polarized cells are largely unknown. We determined mRNA enrichment in TIS granules (TGs) and the rough endopIasmic reticuIum (ER) through particle sorting and isolated cytosolic mRNAs by digitonin extraction. When focusing on non-membrane protein-encoding mRNAs, we observed that 52% have a biased transcript distribution across these compartments. Compartment enrichment is determined by a combinatorial code based on mRNA length, exon length, and 3'UTR-bound RNA-binding proteins. Compartment-biased mRNAs differ in the functional classes of their encoded proteins: TG-enriched mRNAs encode low-abundance proteins with strong enrichment of transcription factors, whereas ER-enriched mRNAs encode large and highly expressed proteins. Compartment localization is an important determinant of mRNA and protein abundance, which is supported by reporter experiments showing that redirecting cytosolic mRNAs to the ER increases their protein expression. In summary, the cytoplasm is functionally compartmentaIized by local translation environments.

molecular biology↗

bioRxiv2022

Single-cell multi-omics decodes regulatory programs during development of mouse secondary palate

The abnormal perturbation in gene regulation during palatogenesis may lead to cleft palate, a major congenital birth defect in humans and mice. However, a comprehensive multi-omic map of the developing secondary palate at single-cell resolution is lacking. In this study, we performed single-cell multiome sequencing and profiled chromatin accessibility and gene expression simultaneously within the same cells (n = 36,154) isolated from mouse secondary palate across embryonic days (E) 12.5, E13.5, E14.0, and E14.5. Application of optimal transport reconstructed five trajectories, representing continuous differentiation of multipotent cells into different subpopulations in later stages. By linking open chromatin signals to gene expression changes, we discovered a list of lineage-determining transcription factors, such as Shox2 for the anterior and Dlx1/2 for the posterior palatal mesenchymal trajectories. In conclusion, this study charted epigenetic and transcriptional dynamics during palatogenesis, which provides a valuable resource for the community and facilitate future research in cleft palate. HighlightsO_LIThe first report on building a single-cell multi-omics atlas with joint chromatin accessibility and gene expression measurements from the same cells during the development of mouse secondary palate. C_LIO_LIApplication of optimal transport calculated fate probabilities to different terminal states and recovered continuous landscapes during mouse secondary palate development. C_LIO_LIBy linking cis-regulatory DNA elements to target genes, we characterized a series of transcription factors governing the differentiation of cranial neural crest-derived multipotent cells to the anterior and posterior palatal mesenchymal trajectories, respectively. C_LIO_LITranscription factors Shox2 and Dlx1/2 exhibited top regulatory roles for the anterior and posterior palatal mesenchymal trajectories, respectively, showing significant enrichment in both motif accessibility and gene expression. C_LI

developmental biology↗

bioRxiv2022

Equalizing epigenetically imprinted centromeres in early mammalian embryos

The CENP-A histone variant epigenetically defines centromeres, where its levels and locations are precisely maintained through mitotic cell divisions. However, differences in centromere CENP-A propagation in soma versus female/male germline remains poorly understood. Here, we generated CenpamScarlet mice and followed CENP-A dynamics in gametes, zygotes, and embryos. We found that, unlike somatic cells, progenitor female and male germ cells carry high centromeric CENP-A levels that decrease upon terminal differentiation. The reduction in CENP-A is differentially regulated between sexes, resulting in a ten-fold higher level in oocytes compared to sperm. In the zygote, the parent-of-origin CENP-A asymmetry is equalized prior to initial S-phase by redistribution of nuclear CENP-A from maternal to paternal chromosomes. Redistribution of CENP-A requires both CDK1/2 and PLK1 centromeric machinery. These experiments provide direct evidence for resetting of epigenetically imprinted centromeres in early pronuclear stage embryos and imply a mechanism to sense the non-equivalency of parental chromosomes. HighlightsO_LIIncreased CENP-A density at centromeres is a conserved property of germline stem cells while CENP-A reduction is coincident with germ cell differentiation C_LIO_LIPaternal and maternal CENP-A containing nucleosomes are intergenerationally inherited C_LIO_LICENP-A density at centromeres differs between male and female mature gametes C_LIO_LIUpon fertilization, maternal nuclear CENP-A is redistributed to equalize with parental CENP-A C_LIO_LICENP-C and MIS18BP1 are asymmetrically enriched in the parental pronuclei in accordance with CENP-A asymmetry. C_LIO_LILicensing for centromere equalization begins before zygotic DNA replication C_LI

developmental biology↗

bioRxiv2022

BrainPy: a flexible, integrative, efficient, and extensible framework towards general-purpose brain dynamics programming

The neural mechanisms underlying brain functions are extremely complicated. Brain dynamics modeling is an indispensable tool for elucidating these mechanisms by modeling the dynamics of the neural circuits that execute brain functions. To ease and facilitate brain dynamics modeling, a general-purpose programming framework is needed to enable users to freely define neural models across multiple scales; efficiently simulate, train, and analyze model dynamics; and conveniently extend new modeling approaches. By utilizing the advanced just-in-time (JIT) compilation, we developed BrainPy. BrainPy provides a rich infrastructure tailored for brain dynamics programming, which supports an integrated platform for brain dynamics model building, simulation, training, and analysis. Models in BrainPy can be JIT compiled into binary instructions for multiple devices (including CPU, GPU, and TPU) to achieve a high running performance comparable to native C or CUDA. Moreover, BrainPy features an extensible architecture allowing easy expansion of new infrastructure, utilities, and machine learning approaches.

neuroscience↗

bioRxiv2022

Identification of plant-derived microRNAs in human kidney

Plant-derived microRNAs (miRNAs) have been implicated as functional regulators in human diseases, although conclusive evidence of this effect remains to be reported. To examine their potential functional role, we profiled the plant-derived miRNAs in 139 blood exosome samples from renal transplantation patients and were able to identify 331 plant-derived miRNAs representing 149 families. According to their miRBase annotation, these miRNAs can be traced back to 76 plant species, most of which are foods common to the human diet (e.g., tomato, soybean, potato and rice). We also profiled 41 blood exosome samples from 22 patients with acute immune rejection (AR) of renal transplants and compared them to 21 samples from 11 patients with stable allograft function to explore possible roles of the functional plant miRNAs. We identified three plant-derived miRNAs (miR4995, miR2118/2218 and miR167) associated with allograft AR whose regulatory targets are mRNAs controlling immune response, T cell activation, and other cellular functions. miR4995 mimics were generated, transfected into HEK293T cells, and their function verified. Our findings not only demonstrate the presence of functional plant-derived miRNAs in human cells, but also provide initial evidence that these miRNAs may be involved in malfunction of renal transplantation.

genetics↗