Biology subjects

Shao, S.

Publications and source records attributed to Shao, S..

48 records · Page 3Linked to original sources

bioRxiv2020

A high-quality genome of the mangrove Aegiceras corniculatum aids investigation of molecular adaptation to intertidal environments

Mangroves have colonized extreme intertidal environments characterized by high salinity, hypoxia, and other abiotic stresses. During millions of years of evolution, mangroves have adapted to these habitats, evolving a series of highly specialized traits. Aegiceras corniculatum, a pioneer mangrove species that evolved salt secretion and crypto-vivipary, is an attractive ecological model to investigate molecular mechanisms underlying adaptation to intertidal environments. Here we report a high-quality reference genome of A. corniculatum using the PacBio SMRT sequencing technology, comprising 827 Megabases (Mb) and containing 32,092 protein-coding genes. The longest scaffold and N50 for the assembled genome are 13.76 Mb and 3.87 Mb. Comparative and evolutionary analyses revealed that A. corniculatum experienced a whole-genome duplication (WGD) event around 35 million years ago after the divergence between Aegiceras and Primula. We inferred that maintenance of cellular environmental homeostasis is an important adaptive process in A. corniculatum. The 14-3-3 protein-coding genes were retained after the recent WGD event, decoding a calcium signal to regulate Na+ homeostasis. A. corniculatum has more H+-ATPase coding genes, essential for the maintenance of low Na+ concentration in the cells, than its relatives. Photosynthesis and oxidative-phosphorylation pathways are overrepresented among significantly expanded gene families and might supply the energy needed for salt secretion. Genes involved in natural antioxidant biosynthesis, contributing to scavenging reactive oxygen species against high salinity, have also increased in copy number. We also found that all homologs of DELAY OF GERMINATION1 (DOG1), a pivotal regulator of seed dormancy, lost their heme-binding ability in A. corniculatum. This loss may contribute to crypto-vivipary. Our study provides a valuable resource to investigate molecular adaptation to extreme environments in mangroves.

genomics↗

bioRxiv2020

Transcriptome analysis of Fenneropenaeus chinensis (Decapoda: Penaeidae) after low-salinity exposure identifies differentially expressed genes in pathways potentially related to osmoregulation

This study investigates the molecular responses of Chinese shrimp (Fenneropenaeus chinensis) to low salinity stress, employing RNA-seq and functional enrichment analyses. A total of 12,332 expressed genes were identified, with 227 differentially expressed genes (DEGs) detected, revealing intricate adaptive responses in gill tissues. Functional enrichment analysis highlighted DEGs associated with ion-transport regulation, bio-metabolism and detoxification (based on GO terms). The upregulation of ATP1A1, SLC26A2, and STK39 suggested a pivotal role of ion-transport regulation, emphasizing the importance of maintaining osmotic balance. In terms of bio-metabolism, ENPP6, GLS, and DMGDH exhibited significant upregulation, indicating adjustments in energy metabolism for low-salinity adaptation. Notably, the downregulation of GSTO1 and CTH raised questions about detoxification pathways, potentially reflecting adaptations or compromises in response to low salinity. Further correlation network analysis highlighted key genes like GLS, STK39, SESN1, and SARDH, revealing intricate relationships among DEGs. RT-qPCR validation confirmed the consistency of gene expression patterns with RNA-seq results. In conclusion, this study provides a comprehensive understanding of the molecular mechanisms underlying Chinese shrimp responses to low salinity stress. The identified genes lay the groundwork for targeted interventions and strategies to enhance shrimp aquaculture system resilience amid changing salinity levels.

physiology↗

bioRxiv2020

Efficient population coding depends on stimulus convergence and source of noise

Sensory organs transmit information to downstream brain circuits using a neural code comprised of spikes from multiple neurons. According to the prominent efficient coding framework, the properties of sensory populations have evolved to encode maximum information about stimuli given biophysical constraints. How information coding depends on the way sensory signals from multiple channels converge downstream is still unknown, especially in the presence of noise which corrupts the signal at different points along the pathway. Here, we calculated the optimal information transfer of a population of nonlinear neurons under two scenarios. First, a lumped-coding channel where the information from different inputs converges to a single channel, thus reducing the number of neurons. Second, an independent-coding channel when different inputs contribute independent information without convergence. In each case, we investigated information loss when the sensory signal was corrupted by two sources of noise. We determined critical noise levels at which the optimal number of distinct thresholds of individual neurons in the population changes. Comparing our system to classical physical systems, these changes correspond to first- or second-order phase transitions for the lumped- or the independent-coding channel, respectively. We relate our theoretical predictions to coding in a population of auditory nerve fibers recorded experimentally, and find signatures of efficient coding. Our results yield important insights into the diverse coding strategies used by neural populations to optimally integrate sensory stimuli in the presence of distinct sources of noise.

neuroscience↗

bioRxiv2019

FLS2 is a CDK-like kinase that directly binds IFT70 and is required for proper ciliary disassembly in Chlamydomonas

Intraflagellar transport (IFT) is required for ciliary assembly and maintenance. While disruption of IFT may trigger ciliary disassembly, we show here that IFT mediated transport of a CDK-like kinase ensures proper ciliary disassembly. Mutations in flagellar shortening 2 (FLS2), encoding a CDK-like kinase, lead to retardation of cilia resorption and delay of cell cycle progression. Stimulation for ciliary disassembly induces gradual dephosphorylation of FLS2 accompanied with gradual inactivation. Loss of FLS2 or its kinase activity induces early onset of kinesin13 phosphorylation in cilia. FLS2 is predominantly localized in the cell body, however, it is transported to cilia upon induction of ciliary disassembly. FLS2 directly interacts with IFT70 and loss of this interaction inhibits its ciliary transport, leading to dysregulation of kinesin13 phosphorylation and retardation of ciliary disassembly. Thus, this work demonstrates that IFT plays active roles in controlling proper ciliary disassembly by transporting a protein kinase to cilia to regulate a microtubule depolymerizer. Author SummaryCilia or eukaryotic flagella are cellular surface protrusions that function in cell motility as well as sensing. They are dynamic structures that undergo assembly and disassembly. Cilia are resorbed during cell cycle progression. Dysregulation of cilia resorption may cause delay of cell cycle progression, which underlies aberrant cell differentiation and even cancer. Ciliary resorption requires depolmerization of axonemal microtubules that is mediated by kinesin13. Using the unicellular green alga, Chlamydomonas, we have identified a CDK-like kinase FLS2 that when mutated retards cilia resorption, leading to delay of cell cycle progression. FLS2, a cell body protein, is transported to cilia via intraflagellar transport upon induction of cilia resorption. FLS2 directly interacts with IFT70 and loss of this interaction inhibits transport of FLS2 to cilia and fails to regulate proper phosphorylation of kinesin13 in cilia.

cell biology↗

bioRxiv2019

LIMD1 phase separation contributes to cellular mechanics and durotaxis by regulating focal adhesion dynamics in response to force

The mechanical environement affects cell morphology, differentiation and motility. The ability of cells to follow gradients of extracellular matrix stiffness-durotaxis has been implicated in development, fibrosis, and cancer. Cells sense and respond to extra-cellular mechanical cues through cell-matrix adhesions. Interestingly, the maturation of focal adhesions (FAs) is reciprocally force-dependent. How biomechanical cues dictate the status of cell motility and how FAs coordinate force sensing and self-organization remain enigmatic. LIMD1, a member of the LIM domain proteins, localizes to the FAs and has been reported to negatively regulate the Hippo-YAP pathway in response to tension. Here we identify the force sensitive recruitment of LIMD1 to the FAs. We discover that LIMD1 regulates cell spreading, maintains FA dynamics and cellular force, and is critical for durotaxis. Intriguingly, LIMD1 selectively recruits late but not early FA proteins through phase separation at the FAs under force. We suggest a model in which localization of LIMD1 to the FAs, triggered by mechanical force, serves as a phase separation hub for assembling and organizing late FA proteins, allowing for effective FA maturation and efficient cellular mechano-transduction.

cell biology↗

bioRxiv2019

Highly Efficient, Massively-Parallel Single-Cell RNA-Seq Reveals Cellular States and Molecular Features of Human Skin Pathology

The development of high-throughput single-cell RNA-sequencing (scRNA-Seq) methodologies has empowered the characterization of complex biological samples by dramatically increasing the number of constituent cells that can be examined concurrently. Nevertheless, these approaches typically recover substantially less information per-cell as compared to lower-throughput microtiter plate-based strategies. To uncover critical phenotypic differences among cells and effectively link scRNA-Seq observations to legacy datasets, reliable detection of phenotype-defining transcripts - such as transcription factors, affinity receptors, and signaling molecules - by these methods is essential. Here, we describe a substantially improved massively-parallel scRNA-Seq protocol we term Seq-Well S^3 (\"Second-Strand Synthesis\") that increases the efficiency of transcript capture and gene detection by up to 10- and 5-fold, respectively, relative to previous iterations, surpassing best-in-class commercial analogs. We first characterized the performance of Seq-Well S^3 in cell lines and PBMCs, and then examined five different inflammatory skin diseases, illustrative of distinct types of inflammation, to explore the breadth of potential immune and parenchymal cell states. Our work presents an essential methodological advance as well as a valuable resource for studying the cellular and molecular features that inform human skin inflammation.

immunology↗

bioRxiv2019

Nuclear actin regulates inducible transcription by enhancing RNA polymerase II clustering

Gene expression in response to external stimuli underlies a variety of fundamental cellular processes. However, how the transcription machinery is regulated under these scenarios is largely unknown. Here, we discover a novel role of nuclear actin in inducible transcriptional regulation using next-generation transcriptome sequencing and super-resolution microscopy. The RNA-seq data reveal that nuclear actin is required for the establishment of the serum-induced transcriptional program. Using super-resolution imaging, we found a remarkable enhancement of RNA polymerase II (Pol II) clustering upon serum stimulation and this enhancement requires the presence of nuclear actin. To study the molecular mechanisms, we firstly observed that Pol II clusters co-localized with the serum-response genes and nuclear actin polymerized in adjacent to Pol II clusters upon serum stimulation. Furthermore, N-WASP and Arp2/3 are reported to interact with Pol II, and we demonstrated N-WASP is required for serum-enhanced Pol II clustering. Importantly, using an optogenetic tool, we revealed that N-WASP phase-separated with the carboxy-terminal domain of Pol II and nuclear actin. In addition to serum stimulation, we found nuclear actin also essential in enhancing Pol II clustering upon interferon-{gamma} treatment. Taken together, our work unveils nuclear actin promotes the formation of transcription factory on inducible genes, acting as a general mechanism underlying the rapid response to environmental cues.

cell biology↗

bioRxiv2019

Chromatin-lamin B1 interaction promotes genomic compartmentalization and constrains chromatin dynamics

The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized chromatin architecture and dynamics remains poorly understood. Here by combining imaging and Hi-C sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to chromatin redistribution and decompaction. Consequently, the inter-chromosomal interactions and overlap between chromosome territories are increased. Moreover, Hi-C data revealed that lamin B1 is required for the integrity and segregation of chromatin compartments but not for the topologically associating domains (TADs). We further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nuclear interior. Taken together, our data suggest that chromatin-lamin B1 interactions promote chromosomal territory segregation and genomic compartmentalization, and confine chromatin dynamics, supporting its crucial role in chromatin higher-order structure and dynamics.

genomics↗

bioRxiv2018

5-HAYED peptide can protect AD brain by scavenging the redundant iron ions and the catalyzed radicals

Alzheimers disease (AD) is a progressive neurodegenerative disease characterized by memory and cognitive decline. It is incurable currently and places a great burden on the caregivers of patients. Iron is rich in the brain of AD suffers. It catalyzes radicals which impairs neurons. Therefore, reducing the redundant brain iron is pressing to ease AD. To scavenge the excessive brain iron catalyzed radical, thus protect the brain and decrease the incidence of AD. We synthesized a soluble iron-pro 5-HAYED peptide. By injecting 5-HAYED to the cerebrospinal fluid (CSF) of the AD mouse, we observed that the 5-HAYED is able to decrease the brain iron and radical level, which behaving neurons protection, and can ameliorate the cognition status for AD mouse. Further, 5-HAYED can decreased the AD incidence and can reverse the AD associated anemia and inflammation without hurt kidney and liver.

neuroscience↗

bioRxiv2017

MapZ forms a stable ring structure that acts as a track for FtsZ treadmilling in Streptococcus mutans

Bacterial binary division requires the accurate placement of the division machinery. FtsZ, the vital component of the division machinery, can assemble into filaments and self-organize into a ring structure (Z-ring) at the proper site for cell division. Thus, understanding how bacteria control the spatiotemporal formation of the FtsZ ring is crucial for small molecule and nanoparticle antibacterial drug discovery. MapZ, a recently identified FtsZ regulator in Streptococcaceae, has been found to localize at the mid-cell and position the FtsZ ring. However, the mechanism is still unclear. Here, by using total internal reflection fluorescence microscopy, super-resolution imaging, and single molecule tracking, we investigated the mechanism by which MapZ regulates the FtsZ ring position. The results show that FtsZ exhibites dynamic treadmilling motion in S. mutans. Importantly, depletion of MapZ leads to an unconstrained movement of treadmilling FtsZ filaments and a shorter lifetime of the constricting FtsZ ring. Furthermore, by revealing that MapZ forms an immobile ring-like nanostructure at the division site, our study suggests that MapZ forms a stable ring that acts as a nanotrack to guide and restrict treadmilling FtsZ filaments in S. mutans, representing a novel way in which bacteria control the division.

microbiology↗

bioRxiv2017

A descending pathway through electrical coupling facilitates undulatory wave propagation in C. elegans

Descending signals from the brain play critical roles in controlling and modulating locomotion kinematics. In the Caenorhabditis elegans nervous system, descending AVB premotor interneurons exclusively form gap junctions with B-type motor neurons that drive forward locomotion. We combined genetic analysis, optogenetic manipulation, and computational modeling to elucidate the function of AVB-B gap junctions during forward locomotion. First, we found that some B-type motor neurons generated intrinsic rhythmic activity, constituting distributed central pattern generators. Second, AVB premotor interneurons drove bifurcation of B-type motor neuron dynamics, triggering their transition from stationary to oscillatory activity. Third, proprioceptive couplings between neighboring B-type motor neurons entrained the frequency of body oscillators, forcing coherent propagation of bending waves. Despite substantial anatomical differences between the worm motor circuit and those in higher model organisms, we uncovered converging principles that govern coordinated locomotion.\n\nSignificance StatementA deep understanding of the neural basis of motor behavior must integrate neuromuscular dynamics, mechanosensory feedback, as well as global command signals, to predict behavioral dynamics. Here, we report on an integrative approach to defining the circuit logic underlying coordinated locomotion in C. elegans. Our combined experimental and computational analysis revealed that (1) motor neurons in C. elegans could function as intrinsic oscillators; (2) Descending inputs and proprioceptive couplings work synergistically to facilitate the sequential activation of motor neuron activities, allowing bending waves to propagate efficiently along the body. Our work thus represents a key step towards an integrative view of animal locomotion.

neuroscience↗

bioRxiv2017

Multiplexed sgRNA Expression Allows Versatile Single Non-repetitive DNA Labeling and Endogenous Gene Regulation

The CRISPR/Cas9 system has made significant contribution to genome editing, gene regulation and chromatin studies in recent years. High-throughput and systematic investigations into the multiplexed biological systems and disease conditions require simultaneous expression and coordinated functioning of multiple sgRNAs. However, current co-transfection based sgRNA co-expression systems remain poorly efficient and virus-based transfection approaches are relatively costly and labor intensive. Here we established a vector-independent method allowing multiple sgRNA expression cassettes to be assembled in series into a single plasmid. This synthetic biology-based strategy excels in its efficiency, controllability and scalability. Taking the flexibility advantage of this all-in-one sgRNA expressing system, we further explored its applications in single non-repetitive genomic locus imaging as well as coordinated gene regulation in live cells. With its strong potency, our method will greatly facilitate the understandings in genome structure, function and dynamics, and will contribute to the systemic investigations into complex physiological and pathological conditions.

synthetic biology↗