Biology subjects

Zhang, T.

Publications and source records attributed to Zhang, T..

At least 361 records · Page 20Linked to original sources

bioRxiv2023

Unravelling Biosynthesis and Biodegradation Potentials of Microbial Dark Matters in Hypersaline Lakes

Biosynthesis and biodegradation of microorganisms critically underpin the development of biotechnology, new drugs and therapies, and environmental remediation. However, the vast majority of uncultured microbial species along with their metabolic capacities in extreme environments remain obscured. To unravel the metabolic potentials of these microbial dark matters (MDMs), we investigated four deep-inland hypersaline lakes with largely diversified environmental parameters in Xinjiang Uygur Zizhiqu, China. Metagenomic binning obtained 3,030 metagenome-assembled genomes (MAGs) spanning 82 phyla, of which 2,363 MAGs could not be assigned to a known genus. These unknown MAGs were abundantly observed with distinct taxa among lakes, possibly linked to the diversification of physiochemical conditions. Analysis of biosynthetic potentials identified 9,635 biosynthesis gene clusters (BGCs), of which 9,403 BGCs were considered novel. We found that some MAGs from putatively novel phyla consistently comprised enriched BGCs, which may have substantial potentials in biotechnological applications. In addition, biodegradation potentials such as dehalogenation, anaerobic ammonium oxidation (Anammox), polycyclic aromatic hydrocarbon (PAH), and plastic degradation were found in new microbial clades from hypersaline lakes. These findings substantially expanded the genetic repository of biosynthesis and biodegradation potentials, which can further assist the development of new and innovative applications in biotechnology.

microbiology↗

bioRxiv2023

Integration of eQTL and Machine Learning Methods to Dissect Causal Genes with Pleiotropic effects in Genetic Regulation Networks of Seed Cotton Yield

Expression quantitative trait loci (eQTL) provide a powerful means of investigating the biological basis of genome-wide association study (GWAS) results and exploring complex traits or phenotypes. In addition to identifying the causal gene in cis, eQTL analysis also reveals a large number of trans-regulated genes located on different chromosomes, which form a gene regulatory network (GRN) that complements the GWAS locus. However, the dissection of a GRN and the crosstalk underlying multiple agronomical traits, along with prioritizing important genes in eQTL-derived GRNs, remains a major challenge. In this study, we generated 558 transcriptional profiles of lint-bearing ovules at one day post-anthesis (DPA) from a selective core cotton germplasm, from which we identified 12,207 eQTLs. By integrating with a GWAS catalog, we found that 66 out of 187 (35.29%) known phenotypic GWAS loci are colocalized with 1,090 eQTLs, forming 38 major functional GRNs predominantly (30 out of 38) associated with seed size-related phenotypes. Of the eGenes, 34 were shared between at least two functional GRNs, exhibiting pleiotropic effects, such as NF-YB3, GRDP1, and IDD7. Narrow-sense heritability analysis showed that the heritability increased with combining the eQTLs with GRNs compared to those with previous yield trait GWAS loci. The extreme gradient boosting (XGBoost) machine learning approach was then applied to predict seed cotton yield phenotypes based on gene expression. Top-ranking eGenes (NF-YB3, FLA2, and GRDP1) derived by XGBoost with pleiotropic effects on yield traits were validated, along with their potential roles by correlation analysis, domestication selection analysis, and transgenic plants. This study provides insights into the mining of GRNs in relation to the pleiotropy of phenotype. The combination of eQTL and machine learning approaches is efficient in improving the genetic dissection of agricultural traits.

genetics↗

bioRxiv2023

Levy statistics define anxiety and depression in mice subjected to chronic stress

IntroductionAnxiety and depression are recognized as adaptive responses to external stressors in organisms. Current methods for evaluating anxiety and depression in rodents are both burdensome and stressful. The objective of this investigation is to explore a simplified methodology for identifying stress-induced and stress-free states, as well as anxiety and depression levels, by analyzing the movement patterns of rodents. MethodsTo address this issue, we utilized Levy statistics to examine the movement patterns of stressed rodents and compared them to non-stressed controls. We employed the two-dimensional Kolmogorov-Smirnov test to identify significant differences in the {gamma} and parameters derived from Levy flight (LF) between anxiety, depression, and control mice. Additionally, we employed the support vector machine algorithm to optimize the classification of each group. ResultsOur analysis revealed that stressed mice displayed heavy-tailed distributions of movement velocity in open fields, resembling the movement patterns observed in animal predators searching for scarce food sources in nature. In contrast, non-stressed mice exhibited a normal distribution of speed. Notably, the effectiveness of this methodology in the field of drug discovery was confirmed by the response of stressed mice to fluoxetine, a well-established selective serotonin reuptake inhibitor (SSRI). ConclusionThis study unveils a previously unidentified statistical walking pattern in mice experiencing anxiety and depression. These findings offer a novel and accessible approach for distinguishing between anxiety, depression, and healthy mice. This method provides a one-step gentle approach (free walk in an open field) instead of the traditional multi-step stressful tests.

animal behavior and cognition↗

bioRxiv2023

How human-derived brain organoids are built differently from brain organoids derived of genetically-close relatives: A multi-scale hypothesis

How genes affect tissue scale organization remains a longstanding biological puzzle. As experimental efforts are underway to solve this puzzle via quantification of gene expression, chromatin organization, cellular structure, and tissue structure, computational modeling efforts remain far behind. To help accelerate the computational modeling efforts, we review two recent publications, the first on a cellular-based model for tissues and the second on a model of a cell nucleus that includes a lamina shell and chromatin. We then address how the two models can be combined to ultimately test multiscale hypotheses linking the chromatin scale and the tissue scale. To be concrete, we turn to an in vitro system for the brain known as a brain organoid. We provide a multiscale hypothesis to distinguish structural differences between brain organoids built from induced-pluripotent human stem cells and from induced-pluripotent gorilla and chimpanzee stem cells. Recent experiments discover that a cell fate transition from neuroepithelial cells to radial glial cells includes a new intermediate state that is delayed in human-derived brain organoids as compared to their genetically-close relatives, which significantly narrows and lengthens the cells on the apical side [1]. Additional experiments revealed that the protein ZEB2 plays a major role in the emergence of this new intermediate state with ZEB2 mRNA levels peaking at the onset of the emergence [1]. We postulate that the enhancement of ZEB2 expression driving this intermediate state is potentially due to chromatin reorganization. More precisely, there exists critical strain triggering the reorganization that is higher for human-derived stem cells, thereby resulting in a delay. Such a hypothesis can readily be tested experimentally within individual cells and within brain organoids as well as computationally to help work towards solving the gene-to-tissue organization puzzle.

developmental biology↗

bioRxiv2023

Peripheral serotonergic neurons regulate anxiety-like behavior and intestinal barrier immunity

Serotonergic circuits in the central nervous system play important roles in regulating mood and behavior, yet the functions of peripheral serotonergic neurons are less understood. Here, we engineered mice lacking the serotonin-producing enzyme Tph2 in peripheral neurons but with intact Tph2 in central neurons. In contrast to mice lacking Tph2 in all neurons, mice lacking Tph2 in peripheral serotonergic neurons did not exhibit increased territorial aggression. However, similar to the total body Tph2 KO mice, the conditional KO animals, exhibited reduced gut motility and decreased anxiety-like behavior. These observations reveal that peripheral serotonergic neurons contribute to control of intestinal motility and anxiety-like behavior and suggest that therapeutics targeting this subset of peripheral neurons could be beneficial.

immunology↗

bioRxiv2023

Contrastive Learning for Sleep Staging based on Inter Subject Correlation

In recent years, multitudes of researches have applied deep learning to automatic sleep stage classification. Whereas actually, these works have paid less attention to the issue of cross-subject in sleep staging. At the same time, emerging neuroscience theories on inter-subject correlations can provide new insights for cross-subject analysis. This paper presents the MViTime model that have been used in sleep staging study. And we implement the inter-subject correlation theory through contrastive learning, providing a feasible solution to address the crosssubject problem in sleep stage classification. Finally, experimental results and conclusions are presented, demonstrating that the developed method has achieved state-of-the-art performance on sleep staging. The results of the ablation experiment also demonstrate the effectiveness of the cross-subject approach based on contrastive learning. The code can be accessed through: https://github.com/jukieCheung/MViTime.

bioengineering↗

bioRxiv2023

A novel bacterial signal transduction system specifically senses and responds to peptidoglycan damage

The peptidoglycan (PG) layer is a mesh-like structure within the cell envelope essential for maintenance of cell shape and resistance to osmotic stress, and therefore is a primary target of many important and widely used antibiotics, such as {beta}-lactams. In Gram-negative bacteria, while signal transduction systems that monitor the state of the inner- and outer-membranes have been extensively studied and well understood, much less is known about how cells sense and respond to PG-targeting stresses. Here we show that a novel bacterial two-component system (PghKR) from Shewanella oneidensis is capable of sensing and responding to PG damage. This system is specifically activated in cells exposed to various PG-targeting antibiotics or carrying a defect in PG synthesis, resulting in induced expression of blaA and relV, which encode a {beta}-lactamase conferring resistance to {beta}-lactams and a small ppGpp synthetase responsible for antibiotic tolerance, respectively. Intriguingly, the PghKR homologs are widespread among several classes of Proteobacteria and the periplasmic domain of sensor kinase PghK contains a family 9 carbohydrate-binding module that is required for signal perception, implying that the signals could be the glycan fragments of PG. Overall, our results provide critical insights into the regulation of PG homeostasis in Gram-negative bacteria.

microbiology↗

bioRxiv2023

Bcl-xL is translocated to the nucleus via CtBP2 to epigenetically promote metastasis

Besides its mitochondria-based anti-apoptotic role, Bcl-xL also travels to the nucleus to promote cancer metastasis by upregulating global histone H3 trimethyl Lys4 (H3K4me3) and TGF{beta} transcription. How Bcl-xL is translocated into the nucleus and how nuclear Bcl-xL regulates H3K4me3 modification are not understood. Here, we report that C-terminal Binding Protein 2 (CtBP2) binds Bcl-xL via its N-terminus and translocates Bcl-xL into the nucleus. Knockdown of CtBP2 by shRNA decreases the nuclear portion of Bcl-xL and reverses Bcl-xL-induced cell migration and metastasis in mouse models. Furthermore, knockout of CtBP2 suppresses Bcl-xL transcription. The binding between Bcl-xL and CtBP2 is required for their interaction with MLL1, a histone H3K4 methyltransferase. Pharmacologic inhibition of MLL1 enzymatic activity reverses Bcl-xL-induced H3K4me3 and TGF{beta} mRNA upregulation as well as cell invasion. Moreover, cleavage under targets and release using nuclease (CUT&RUN) coupled with next generation sequencing reveals that H3K4me3 modifications are particularly enriched in the promotor region of genes encoding TGF{beta} and its signaling pathway in the cancer cells overexpressing Bcl-xL. Altogether, the metastatic function of Bcl-xL is mediated by its interaction with CtBP2 and MLL1.

cancer biology↗

bioRxiv2023

High-resolution structure of a mercury cross-linked ZIP metal transporter reveals delicate motions and metal relay for regulated zinc transport

Zrt-/Irt-like protein (ZIP) divalent metal transporters play a central role in maintaining trace element homeostasis. The prototypical ZIP from Bordetella bronchiseptica (BbZIP) is an elevator-type transporter, but the dynamic motions and detailed transport mechanism remain to be elucidated. Here, we report a high-resolution crystal structure of a mercury-crosslinked BbZIP variant at 1.95 [A], revealing an upward rotation of the transport domain in the new inward-facing conformation and a water-filled metal release channel that is divided into two parallel pathways by the previously disordered cytoplasmic loop. Mutagenesis and transport assays indicated that the newly identified high-affinity metal binding site in the primary pathway acts as a "metal sink" to reduce the transport rate. The discovery of a hinge motion around an extracellular axis allowed us to propose a sequential hinge-elevator-hinge movement of the transport domain to achieve alternating access. These findings provide key insights into the transport mechanisms and activity regulation.

biochemistry↗

bioRxiv2023

Computational ranking-assisted identification of Plexin-B2 in homotypic and heterotypic clustering of circulating tumor cells in breast cancer metastasis

Metastasis is the cause of over 90% of all deaths associated with breast cancer, yet the strategies to predict cancer spreading based on primary tumor profiles and therefore prevent metastasis are egregiously limited. As rare precursor cells to metastasis, circulating tumor cells (CTCs) in multicellular clusters in the blood are 20-50 times more likely to produce viable metastasis than single CTCs. However, the molecular mechanisms underlying various CTC clusters, such as homotypic tumor cell clusters and heterotypic tumor-immune cell clusters, are yet to be fully elucidated. Combining machine learning-assisted computational ranking with experimental demonstration to assess cell adhesion candidates, we identified a transmembrane protein Plexin- B2 (PB2) as a new therapeutic target that drives the formation of both homotypic and heterotypic CTC clusters. High PB2 expression in human primary tumors predicts an unfavorable distant metastasis-free survival and is enriched in CTC clusters compared to single CTCs in advanced breast cancers. Loss of PB2 reduces formation of homotypic tumor cell clusters as well as heterotypic tumor-myeloid cell clusters in triple-negative breast cancer. Interactions between PB2 and its ligand Sema4C on tumor cells promote homotypic cluster formation, and PB2 binding with Sema4A on myeloid cells (monocytes) drives heterotypic CTC cluster formation, suggesting that metastasizing tumor cells hijack the PB2/Sema family axis to promote lung metastasis in breast cancer. Additionally, using a global proteomic analysis, we identified novel downstream effectors of the PB2 pathway associated with cancer stemness, cell cycling, and tumor cell clustering in breast cancer. Thus, PB2 is a novel therapeutic target for preventing new metastasis.

cancer biology↗

bioRxiv2023

Characterization of mitotic phenotypes associated with a MYC synthetic lethal compound

Therapeutic targeting of MYC directly has proven difficult, but several means to target MYC indirectly using a synthetic lethal drug approach have been proposed. Synthetic lethal approaches for MYC have sought to take advantage of vulnerabilities MYC imposes related to either metabolic reprogramming, apoptotic signaling or the cycling of cancer cells. Here, we describe in detail the cell division phenotypes induced by a MYC synthetic lethal compound, dimethylfasudil (diMF). DiMF is a known ROCK inhibitor, but structurally related ROCK inhibitors are not synthetic lethal with MYC, so the activity of diMF is not related to blockade of this family of kinases. Instead, this compound induced multiple cell cycle-related liabilities. These included the early mitotic arrest of cycling cells followed by mitotic catastrophe-induced death and the induction of polyploidy in cells that do manage to pass through mitosis. As early as prometaphase, we noted diminished staining for BUB1 kinase, which binds to kinetochores and regulates the mitotic spindle checkpoint and chromosome congression. Kinetochore proteins, such as CENP-F, failed to localize at the metaphase plate, confirming a deficit in centromere assembly. This, presumably, contributed to the development of segregation anomalies in diMF-treated cells. In anaphase cells, the protein regulator of cytokinesis 1 (PRC1), failed to be recruited to the midzone, leading to a cascade of defects that included failed recruitment of the chromosomal passenger protein complex, the centralspindlin complex and polo-like-kinase 1 (PLK1). These observations correlate well with the cell death phenotypes induced by diMF, which may serve as a prototype MYC synthetic lethal compound to explore synthetic lethal therapy or as a scaffold upon which to build superior compounds. The phenotypes described here serve as examples of MYC synthetic lethal drug effects that can be used to explore and maximize drug discovery programs.

cancer biology↗

bioRxiv2023

Loss of MC1R signaling implicates TBX3 in pheomelanogenesis and melanoma predisposition

The human Red Hair Color (RHC) trait is caused by increased pheomelanin (red-yellow) and reduced eumelanin (black-brown) pigment in skin and hair due to diminished melanocortin 1 receptor (MC1R) function. In addition, individuals harboring the RHC trait are predisposed to melanoma development. While MC1R variants have been established as causative of RHC and are a well-defined risk factor for melanoma, it remains unclear mechanistically why decreased MC1R signaling alters pigmentation and increases melanoma susceptibility. Here, we use single-cell RNA-sequencing (scRNA-seq) of melanocytes isolated from RHC mouse models to reveal a Pheomelanin Gene Signature (PGS) comprising genes implicated in melanogenesis and oncogenic transformation. We show that TBX3, a well-known anti-senescence transcription factor implicated in melanoma progression, is part of the PGS and binds both E-box and T-box elements to regulate genes associated with melanogenesis and senescence bypass. Our results provide key insights into mechanisms by which MC1R signaling regulates pigmentation and how individuals with the RHC phenotype are predisposed to melanoma.

genetics↗

bioRxiv2023

Inhibition mechanism and antiviral activity of an α-ketoamide based SARS-CoV-2 main protease inhibitor

SARS-CoV-2 has demonstrated extraordinary ability to evade antibody immunity by antigenic drift. Small molecule drugs may provide effective therapy while being part of a solution to circumvent SARS-CoV-2 immune escape. In this study we report an -ketoamide based peptidomimetic inhibitor of SARS-CoV-2 main protease (Mpro), RAY1216. Enzyme inhibition kinetic analysis established that RAY1216 is a slow-tight inhibitor with a Ki of 8.6 nM; RAY1216 has a drug-target residence time of 104 min compared to 9 min of PF-07321332 (nirmatrelvir), the antiviral component in Paxlovid, suggesting that RAY1216 is approximately 12 times slower to dissociate from the protease-inhibitor complex compared to PF-07321332. Crystal structure of SARS-CoV-2 Mpro:RAY1216 complex demonstrates that RAY1216 is covalently attached to the catalytic Cys145 through the -ketoamide warhead; more extensive interactions are identified between bound RAY1216 and Mpro active site compared to PF-07321332, consistent with a more stable acyl-enzyme inhibition complex for RAY1216. In cell culture and human ACE2 transgenic mouse models, RAY1216 demonstrates comparable antiviral activities towards different SARS-CoV-2 virus variants compared to PF-07321332. Improvement in pharmacokinetics has been observed for RAY1216 over PF-07321332 in various animal models, which may allow RAY1216 to be used without ritonavir. RAY1216 is currently undergoing phase III clinical trials (https://clinicaltrials.gov/ct2/show/NCT05620160) to test real-world therapeutic efficacy against COVID-19.

biochemistry↗

bioRxiv2023

A bile metabolite atlas reveals infection-triggered interorgan mediators of intestinal homeostasis and defense

An essential function of the liver is the formation of bile. This aqueous solution is critical for fat absorption and is transported to the duodenum via the common bile duct. Despite extensive studies of bile salts, other components of bile are less well-charted. Here, we characterized the murine bile metabolome and investigated how the microbiota and enteric infection influence bile composition. We discovered that the bile metabolome is not only substantially more complex than appreciated but is dynamic and responsive to the microbiota and enteric infection. Hepatic transcriptomics identified enteric infection-triggered pathways that likely underlie bile remodeling. Enteric infections stimulated elevation of four dicarboxylates in bile that modulated intestinal gut epithelial and microbiota composition, inflammasome activation, and host defense. Our data suggest that enteric infection-associated signals are relayed between the intestine and liver and induce transcriptional programs that shape the bile metabolome, modifying biles immunomodulatory and host defense functions.

microbiology↗

bioRxiv2023

Fast and accurate DNASeq Variant Calling workflow composed of LUSH toolkit

BackgroundWhole genome sequencing (WGS) is becoming increasingly prevalent for molecular diagnosis, staging and prognosis because of its declining costs and the ability to detect nearly all genes associated with a patients disease. The currently widely accepted variant calling pipeline, GATK, is limited in terms of its computational speed and efficiency, which cannot meet the growing analysis needs. MethodsIn this study, we propose a fast and accurate DNASeq variant calling workflow that is purely composed of tools from LUSH toolkit. The LUSH pipeline is highly optimized for the WGS pipeline based on SOAPnuke, BWA and GATK which can be deployed on any general-purpose CPU-based computing system. We validated the accuracy, speed and scalability of the LUSH pipeline on several standard WGS datasets. ResultsOur test results show that the LUSH pipeline and the GATK pipeline are highly consistent in terms of accuracy, achieving over 99% precision and recall on NA12878. For speed, the LUSH pipeline completes 30x WGS data in 1.6 hours, which is about 17x faster than the GATK pipeline. From BAM to VCF, LUSH_HC even takes only 12 minutes, about 76x faster than GATK. Moreover, the LUSH pipeline shows favorable scalability in terms of thread and sequencing depth. ConclusionThe LUSH pipeline provides far superior computational speed to GATK while maintaining a high level of accuracy comparable to that of GATK, which greatly facilitates bedside analysis of acute patients, large-scale cohort data analysis, and variant calling in crop breeding programs.

bioinformatics↗

bioRxiv2023

Novel Evoked Synaptic Activity Potentials (ESAPs) elicited by Spinal Cord Stimulation

Spinal cord stimulation (SCS) evokes fast epidural Evoked Compound Action Potential (ECAPs) that represent activity of dorsal column axons, but not necessarily a spinal circuit response. Using a multimodal approach, we identified and characterized a delayed and slower potential evoked by SCS that reflects synaptic activity within the spinal cord. Anesthetized female Sprague Dawley rats were implanted with an epidural SCS lead, epidural motor cortex stimulation electrodes, an epidural spinal cord recoding lead, an intraspinal penetrating recording electrode array, and intramuscular electromyography (EMG) electrodes in the hindlimb and back. We stimulated the motor cortex or the epidural spinal cord and recorded epidural, intraspinal, and EMG responses. SCS pulses produced characteristic propagating ECAPs (composed of P1, N1, and P2 waves with latencies <2 ms) and an additional wave ("S1") starting after the N2. We verified the S1-wave was not a stimulation artifact and was not a reflection of hindlimb/back EMG. The S1-wave has a distinct stimulation-intensity dose response and spatial profile compared to ECAPs. CNQX (a selective competitive antagonist of AMPA receptors) significantly diminished the S1-wave, but not ECAPs. Furthermore, cortical stimulation, which did not evoke ECAPs, produced epidurally detectable and CNQX-sensitive responses at the same spinal sites, confirming epidural recording of an evoked synaptic response. Finally, applying 50 Hz SCS resulted in dampening of ESAPs, but not ECAPs. Therefore, we hypothesize that the S1-wave is synaptic in origin, and we term the S1-wave type responses: Evoked Synaptic Activity Potentials (ESAPs). The identification and characterization of epidurally recorded ESAPs from the dorsal horn may elucidate SCS mechanisms. Significance StatementSpinal cord stimulation (SCS) is an established treatment for chronic pain and has applications to other disorders and neurorehabilitation. Notwithstanding decades of trials and research, questions remain about SCS mechanisms of action - and indicators thereof. Recent technological developments have enabled the detection of Evoked Compound Action Potential (ECAPs) - reflecting synchronous activity of the dorsal column axons activated by SCS. However, ECAP is not a direct measure of sensory processing in the dorsal horn. Here, we identify and characterize a novel electrophysiological signal that is evoked and detectable by epidural SCS electrodes and reflects spinal synaptic currents. This new signal, termed an Evoked Synaptic Activity Potential (ESAP), is thus a novel means with which to interrogate spinal gray matter circuits during SCS.

neuroscience↗

bioRxiv2023

ADAM10 mediates macroglial cell fate decisions in the developing brain

ADAMs (a disintegrin and metalloproteinase) are transmembrane proteins with cell adhesion and protease activities that contain disintegrin and metalloproteinase domains. ADAM10, a member of the ADAM family, is widely expressed in the brain. There are >40 substrates reported for ADAM10, including Notch, Delta-like ligand-1 (Dll1), and N-cadherin. To date, however, its function in the brain has been largely unknown. We used genetic manipulation to delete Adam10 specifically from glial progenitors in developing brains and observed that conditional knockout mice showed locomotor abnormalities. They all died within 4 months with apparent defects in the cerebellum. By comprehensively analyzing data from bulk RNA sequencing, single-cell RNA sequencing, and staining of the cerebellum, we found that ADAM10 promoted astrocyte generation under physiological conditions. Upon the removal of Adam10 in glial progenitors, the production of oligodendrocytes vastly increased, whereas the generation of astrocytes was substantially inhibited. Our results showed that ADAM10 plays a critical role in macroglial cell fate decisions during brain development.

neuroscience↗

bioRxiv2023

Single-cell RNA sequencing reveals cellular and molecular heterogeneity in fibrocartilaginous enthesis formation

The attachment site of the rotator cuff (RC) is a classic fibrocartilaginous enthesis, which is the junction between bone and tendon with typical characteristics of a fibrocartilage transition zone. Enthesis development has historically been studied with lineage tracing of individual genes selected a priori, which does not allow for the determination of single-cell landscapes yielding mature cell types and tissues. Here, we applied Single-cell RNA sequencing (scRNA-seq) to delineate the comprehensive postnatal RC enthesis growth and the temporal atlas from as early as embryonic day 15 up to postnatal week 4. In summary, we compared the development pattern between enthesis and tendon or articular cartilage, then deciphered the cellular heterogeneity and the molecular dynamics during fibrocartilage differentiation. This data provides a transcriptional resource that will support future investigations of enthesis development at the mechanistic level and may shed light on the strategies for enhanced RC healing outcomes.

developmental biology↗