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Huang, J.

Publications and source records attributed to Huang, J..

At least 289 records · Page 16Linked to original sources

scDTL: single-cell RNA-seq imputation based on deep transfer learning using bulk cell information

MotivationThe growing amount of single-cell RNA sequencing (scRNA-seq) data allows researchers to investigate cellular heterogeneity and gene expression profiles, providing a high-resolution view of transcriptome at the single-cell level. However, dropout events, which are often present in scRNA-seq data, remain challenges for downstream analysis. Although a number of studies have been developed to recover single-cell expression profiles, their performance is sometimes limited by not fully utilizing the inherent relations between genes. ResultsTo address the issue, we propose a deep transfer learning based approach called scDTL for scRNA-seq data imputation by exploring the bulk RNA-sequencing information. scDTL firstly trains an imputation model for bulk RNA-seq data using a denoising autoencoder (DAE). We then apply a domain adaptation architecture that builds a mapping between bulk gene and single-cell gene domains, which transfers the knowledge learned by the bulk imputation model to scRNA-seq learning task. In addition, scDTL employs a parallel operation with a 1D U-Net denoising model to provide gene representations of varying granularity, capturing both coarse and fine features of the scRNA-seq data. At the final step, we use the cross-channel attention mechanism to fuse the features learned from the transferred bulk imputer and U-Net model. In the evaluation, we conduct extensive experiments to demonstrate that scDTL based approach could outperform other state-of-the-art methods in the quantitative comparison and downstream analyses. Contactzhangd@szu.edu.cn or tianj@sustech.edu.cn

bioinformatics↗

Mapping the Cellular Biogeography of Human Bone Marrow Niches Using Single-Cell Transcriptomics and Proteomic Imaging

The bone marrow is the organ responsible for blood production. Diverse non-hematopoietic cells contribute essentially to hematopoiesis. However, these cells and their spatial organization remain largely uncharacterized as they have been technically challenging to study in humans. Here, we used fresh femoral head samples and performed single-cell RNA sequencing (scRNA-Seq) to profile 29,325 enriched non-hematopoietic bone marrow cells and discover nine transcriptionally distinct subtypes. We next employed CO-detection by inDEXing (CODEX) multiplexed imaging of 18 individuals, including both healthy and acute myeloid leukemia (AML) samples, to spatially profile over one million single cells with a novel 53-antibody panel. We discovered a relatively hyperoxygenated arterio-endosteal niche for early myelopoiesis, and an adipocytic, but not endosteal or perivascular, niche for early hematopoietic stem and progenitor cells. We used our atlas to predict cell type labels in new bone marrow images and used these predictions to uncover mesenchymal stromal cell (MSC) expansion and leukemic blast/MSC-enriched spatial neighborhoods in AML patient samples. Our work represents the first comprehensive, spatially-resolved multiomic atlas of human bone marrow and will serve as a reference for future investigation of cellular interactions that drive hematopoiesis.

cell biology↗

Astrocytes control quiescent NSC reactivation via GPCR signaling-mediated F-actin remodeling

The transitioning of neural stem cells (NSCs) between quiescent and proliferative states is fundamental for brain development and homeostasis. Defects in NSC reactivation are associated with neurodevelopmental disorders. Drosophila quiescent NSCs extend an actin-rich primary protrusion toward the neuropil. However, the function of the actin cytoskeleton during NSC reactivation is unknown. Here, we reveal the fine F-actin structures in the protrusions of quiescent NSCs by expansion and super-resolution microscopy. We show that F-actin polymerization promotes the nuclear translocation of Mrtf, a microcephaly-associated transcription factor, for NSC reactivation and brain development. F-actin polymerization is regulated by a signaling cascade composed of G-protein-coupled receptor (GPCR) Smog, G-protein q subunit, Rho1 GTPase, and Diaphanous (Dia)/Formin during NSC reactivation. Further, astrocytes secrete a Smog ligand Fog to regulate Gq-Rho1-Dia-mediated NSC reactivation. Together, we establish that the Smog-Gq-Rho1 signaling axis derived from astrocytes, a NSC niche, regulates Dia-mediated F-actin dynamics in NSC reactivation.

developmental biology↗

Cdon is required for organ Left-Right patterning via regulating DFCs migration and the sequential ciliogenesis

Cdon and boc are members of the cell adhesion molecule subfamily III Ig/fibronectin. Although they were reported to be involved in muscle and neural development at late developmental stage, while their early roles in embryonic development are unknown. Here we discovered that zebrafish cdon but not boc was expressed in dorsal forerunner cells (DFCs) and epitheliums of Kupffers vesicle (KV), implying the possible role of cdon in organ LR patterning. Further data showed that the liver and heart LR patterning was disturbed in cdon morphants and cdon mutants. Mechanically, we found that cdon loss of function led to dispersed DFCs migration, smaller KV and defective ciliogenesis, which resulting in randomized Nodal/spaw signaling and the sequential organ LR patterning defect. Finally, predominant distribution of a cdon MO in DFCs led to defects in DFCs migration, KV morphogenesis/ciliogenesis, Nodal/spaw signaling and organ LR asymmetry, being similar to those in cdon morphants and cdon-/- embryos, indicating a cell-autonomous role of cdon in regulating KV formation and ciliogenesis during LR patterning. In conclusion, our data demonstrated that, during gastrulation stage and early somitogenesis stage, cdon is required for proper DFCs migration, KV formation and ciliogenesis, thus playing an important role in setting up organ LR asymmetry.

developmental biology↗

TREM1 disrupts myeloid bioenergetics and cognitive function in aging and Alzheimer disease models

Human genetics implicate defective myeloid responses in the development of late onset, age-associated Alzheimers disease (AD). Aging is characterized by a decline in myeloid metabolism that triggers maladaptive, neurotoxic immune responses. TREM1 is an amplifier of pro-inflammatory myeloid responses, and here we find that Trem1 deficiency prevents age-dependent changes in myeloid metabolism, inflammation, and hippocampal memory function. Trem1 deficiency rescues age-associated declines in ribose-5P, a glycolytic intermediate and the precursor for purine, pyrimidine, and NAD+ biosynthesis. In vitro, Trem1 deficient microglia are resistant to bioenergetic changes induced by amyloid-{beta}42 oligomers (A{beta}42), suggesting that A{beta}42 stimulation disrupts homeostatic microglial metabolism and immune function via TREM1. In the 5XFAD model of amyloid accumulation, Trem1 haploinsufficiency prevents spatial memory loss, preserves homeostatic microglial morphology, and reduces neuritic dystrophy independent of amyloid accumulation or changes in the disease-associated microglial transcriptomic signature. In aging APPSwe mice, Trem1 deficiency restores synaptic mitochondrial function and cerebral glucose uptake and prevents hippocampal memory decline. In post-mortem human brain, microglial TREM1 expression increases with clinical and neuropathological severity. Thus, TREM1-mediated disruption of myeloid metabolism, both in the periphery and brain, promotes cognitive decline in aging and amyloid accumulation, two major risk factors for AD development.

neuroscience↗

Post-death Vesicles of Senescent Bone Marrow Mesenchymal Stromal Polyploids Promote Macrophage Aging and Breast Cancer

Potential systemic factors contributing to aging-associated breast cancer (BC) remain elusive. Here, we reveal that the polyploid giant cells (PGCs) that contain more than two sets of genomes prevailing in aging and cancerous tissues constitute 5-10% of healthy female bone marrow mesenchymal stromal cells (fBMSCs). The PGCs can repair DNA damage and stimulate neighboring cells for clonal expansion. However, dying PGCs in advanced-senescent fBMSCs can form "spikings" which are then separated into membraned mtDNA-containing vesicles (Senescent PGC-Spiking Bodies; SPSBs). SPSB-phagocytosed macrophages accelerate aging with diminished clearance on BC cells and protumor M2 polarization. SPSB-carried mitochondrial OXPHOS components are enriched in BC of elder patients and associated with poor prognosis. SPSB-incorporated breast epithelial cells develop aggressive characteristics and PGCs resembling the polyploid giant cancer cells (PGCCs) in clonogenic BC cells and cancer tissues. These findings highlight an aging BMSC-induced BC risk mediated by SPSB-induced macrophage dysfunction and epithelial cell precancerous transition. SIGNIFICANCEMechanisms underlying aging-associated cancer risk remain unelucidated. This work demonstrates that polyploid giant cells (PGCs) in bone marrow mesenchymal stromal cells (BMSCs) from healthy female bone marrow donors can boost neighboring cell proliferation for clonal expansion. However, the dying-senescent PGCs in the advanced-senescent fBMSCs can form "spikings" which are separated into mitochondrial DNA (mtDNA)-containing spiking bodies (senescent PGC-spiking bodies; SPSBs). The SPSBs promote macrophage aging and breast epithelial cell protumorigenic transition and form polyploid giant cancer cells. These results demonstrate a new form of ghost message from dying-senescent BMSCs, that may serve as a systemic factor contributing to aging-associated immunosuppression and breast cancer risk. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/583755v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@f07b60org.highwire.dtl.DTLVardef@33ef98org.highwire.dtl.DTLVardef@1b720c8org.highwire.dtl.DTLVardef@1c9514d_HPS_FORMAT_FIGEXP M_FIG Xie et al demonstrate that the polyploid giant cells (PGCs) in the juvenile phase expansion of female bone marrow mesenchymal stromal cells (fBMSCs) can boost neighboring cell proliferation for clonal expansion. However, when fBMSCs enter to the advanced-senescent phase, the dying-senescent PGCs form "spikings" which are then separated into membraned vesicles termed Senescent PGC spiking bodies, SPSBs). The SPSBs carrying fragmented mitochondrial elements and OXPHOS proteins can be phagocytosed by macrophage and breast epithelial cells leading to macrophage aging and breast epithelial protumorigenic transition. The SPSBs are demonstrated to be a new form of post-cell death vesicle from aging BMSCs and may serve as a systemic factor contributing to aging-associated immunosuppression and breast cancer risk. C_FIG

cancer biology↗

Developing Bioactive Hydrogels Containing Cell-derived Extracellular Matrix: Implications in Drug and Cell-free Bone and Cartilage Repair

The prevalence of osteoarthritis has been increasing in aging populations, which has necessitated the use of advanced biomedical treatments. These involve grafts or delivering drug molecules entrapped in scaffolds. However, such treatments often show suboptimal therapeutic effects due to poor half-life and off-target effects of drug molecules. This study aims to overcome these limitations by 3D printing gelatin-based hydrogel scaffolds containing cell-derived extracellular matrix (ECM) as the bioactive therapeutic cargo. Here, pre-osteoblastic and pre-chondrogenic murine cells were differentiated in vitro, decellularized, and incorporated into methacrylated gelatin (GelMA) solutions to form osteogenic (GelO) and chondrogenic (GelC) hydrogels, respectively. The integration of the bioactive decellularized extracellular matrix (dECM) allows GelO and GelC to induce differentiation in human adipose-derived stem cells (hADSCs) toward osteogenic and chondrogenic lineages. GelO and GelC can be covalently adhered using carbodiimide coupling reaction, forming bioactive osteochondral plug. Moreover, this osteochondral plug can also induce differentiation of hADSCs. To conclude, this ECM-based bioactive hydrogel offers a promising new drug-free and cell-free treatment strategy for bone and cartilage repair, and future osteoarthritis management.

bioengineering↗

PNAbind: Structure-based prediction of protein-nucleic acid binding using graph neural networks

The recognition and binding of nucleic acids (NAs) by proteins depends upon complementary chemical, electrostatic and geometric properties of the protein-NA binding interface. Structural models of protein-NA complexes provide insights into these properties but are scarce relative to models of unbound proteins. We present a deep learning approach for predicting protein-NA binding given the apo structure of a protein (PNAbind). Our method utilizes graph neural networks to encode spatial distributions of physicochemical and geometric properties of the protein molecular surface that are predictive of NA binding. Using global physicochemical encodings, our models predict the overall binding function of a protein and can discriminate between specificity for DNA or RNA binding. We show that such predictions made on protein structures modeled with AlphaFold2 can be used to gain mechanistic understanding of chemical and structural features that determine NA recognition. Using local encodings, our models predict the location of NA binding sites at the level of individual binding residues. Binding site predictions were validated against benchmark datasets, achieving AUROC scores in the range of 0.92-0.95. We applied our models to the HIV-1 restriction factor APOBEC3G and show that our predictions are consistent with experimental RNA binding data.

bioinformatics↗

Psychological stress disturbs bone metabolism via miR-335-3p/Fos signaling in osteoclast

It has been well-validated that chronic psychological stress leads to bone loss, but the underlying mechanism remains unclarified. In this study, we established and analyzed the chronic unpredictable mild stress (CUMS) mice to investigate the miRNA-related pathogenic mechanism involved in psychological stress induced osteoporosis. Our result found that these CUMS mice exhibited osteoporosis phenotype that mainly attributed to the abnormal activities of osteoclasts. Subsequently, miRNA sequencing and other analysis showed that miR-335-3p, which is normally highly expressed in the brain, was significantly down-regulated in the nucleus ambiguous (NAC), serum, and bone of the CUMS mice. Additionally, in vitro studies detected that miR-335-3p is important for osteoclast differentiation, with its direct targeting site in FOS. Further studies demonstrated FOS was upregulated in CUMS osteoclast, and the inhibition of FOS suppressed the accelerated osteoclastic differentiation, as well as the expression of osteoclastic genes, such as Nfatc1, Acp5, Mmp9, in miR-335-3p restrained osteoclasts. In conclusion, this work indicated that psychological stress may down-regulate the miR-335-3p expression, which resulted in the accumulation of FOS and the up-regulation of NFACT1 signaling pathway in osteoclasts, leading to its accelerated differentiation and abnormal activity. These results decipher a previously unrecognized paradigm that miRNA can act as a link between psychological stress and bone metabolism. Impact statementmiR-335-3p, which targets FOS and inhibits its activation of NFATC1 signaling, is an important regulator for osteoclast function and responsible for the psychological stress induced osteoporosis

neuroscience↗

DNA Methylome Regulates Virulence and Metabolism in Pseudomonas syringae

Bacterial pathogens employ epigenetic mechanisms, including DNA methylation, to adapt to environmental changes, and these mechanisms play important roles in various biological processes. Pseudomonas syringae is a model phytopathogenic bacterium, but its methylome is less well known than that of other species. In this study, we conducted single-molecule real-time sequencing to profile the DNA methylation landscape in three model pathovars of P. syringae. We identified one Type-I restriction-modification system (HsdMSR), including the conserved sequence motif associated with N6-methyladenine (6mA). About 25%-40% of the genes involved in DNA methylation were conserved in two or more of the strains, revealing the functional conservation of methylation in P. syringae. Subsequent transcriptomic analysis highlighted the involvement of HsdMSR in virulent and metabolic pathways, including the Type III secretion system, biofilm formation, and translational efficiency. The regulatory effect of HsdMSR on transcription was dependent on both strands being fully 6mA methylated. Overall, this work illustrated the methylation profile in P. syringae and the critical involvement of DNA methylation in regulating virulence and metabolism. Thus, this work contributes to a deeper understanding of epigenetic transcriptional control in P. syringae and related bacteria.

microbiology↗

Loss of function in RBBP5 results in a syndromic neurodevelopmental disorder associated with microcephaly

PurposeEpigenetic dysregulation has been associated with many inherited disorders. RBBP5 encodes a core member of the protein complex that methylates histone 3 lysine-4 (H3K4) and has not been implicated in human disease. MethodsWe identify five unrelated individuals with de novo heterozygous pathogenic variants in RBBP5. Three truncating and two missense variants were identified in probands with neurodevelopmental symptoms including global developmental delay, intellectual disability, microcephaly, and short stature. Here, we investigate the pathogenicity of the variants through protein structural analysis and transgenic Drosophila models. ResultsBoth missense p.T232I and p.E296D variants affect evolutionarily conserved amino acids and are expected to interfere with the interface between RBBP5 and the histones. In Drosophila, ubiquitous overexpression of human RBBP5 is lethal in the larval developmental stage. Loss of Rbbp5 leads to a reduction in brain size, and the human reference, p.T232I, or p.E296D variant transgenes fail to rescue loss of Rbbp5. Expression of either missense variant in an Rbbp5 null background results in a less severe microcephaly phenotype than the human reference, indicating both p.T232I and p.E296D variants are loss-of-function alleles. ConclusionDe novo heterozygous variants in RBBP5 are associated with a syndromic neurodevelopmental disorder. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=193 HEIGHT=200 SRC="FIGDIR/small/578086v1_ufig1.gif" ALT="Figure 1"> O_LINKSMALLFIG WIDTH=200 HEIGHT=24 SRC="FIGDIR/small/578086v1_ufig1a.gif" ALT="Figure 1"> View larger version (59K): org.highwire.dtl.DTLVardef@11337daorg.highwire.dtl.DTLVardef@b7f4d8org.highwire.dtl.DTLVardef@12bc283org.highwire.dtl.DTLVardef@1ef4e09_HPS_FORMAT_FIGEXP M_FIG C_FIG

genetics↗

A mathematical framework for understanding the spontaneous emergence of complexity applicable to growing multicellular systems

In embryonic development and organogenesis, cells sharing identical genetic codes acquire diverse gene expression states in a highly reproducible spatial distribution, crucial for multicellular formation and quantifiable through positional information. To understand the spontaneous growth of complexity, we constructed a one-dimensional division-decision model, simulating the growth of cells with identical genetic networks from a single cell. Our findings highlight the pivotal role of cell division in providing positional cues, escorting the system toward states rich in information. Moreover, we pinpointed lateral inhibition as a critical mechanism translating spatial contacts into gene expression. Our model demonstrates that the spatial arrangement resulting from cell division, combined with cell lineages, imparts positional information, specifying multiple cell states with increased complexity--illustrated through examples in C.elegans. This study constitutes a foundational step in comprehending developmental intricacies, paving the way for future quantitative formulations to construct synthetic multicellular patterns.

systems biology↗

Genomic and environmental controls on Castellaniella biogeography in an anthropogenically disturbed subsurface

Castellaniella species have been isolated from a variety of mixed-waste environments including the nitrate and multiple metal contaminated subsurface at the Oak Ridge Reservation (ORR). Previous studies examining microbial community composition and nitrate removal at ORR during biostimulation efforts reported increased abundances of members of the Castellaniella genus concurrent to increased denitrification rates. Thus, we asked how genomic and abiotic factors control the Castellaniella biogeography at the site to understand how these factors may influence nitrate transformation in an anthropogenically impacted setting. ORR Castellaniella strains showed a higher degree of genetic diversification than those originating from non-ORR sites, which we attribute to the multitude of extreme stressors faced in the ORR subsurface. We report the isolation and characterization of several Castellaniella strains from the ORR subsurface. Five of these isolates match at 100% identity (at the 16S rRNA gene V4 region) to two Castellaniella amplicon sequence variants (ASVs), ASV1 and ASV2, that have persisted in the ORR subsurface for at least two decades. However, ASV2 has consistently higher relative abundance in samples taken from the site and was also the dominant blooming denitrifier population during a prior biostimulation effort. We found that the ASV2 representative strain has greater resistance to mixed metal stress than the ASV1 representative strains. We attribute this resistance, in part, to the large number of unique heavy metal resistance genes identified on a genomic island in the ASV2 representative genome. Additionally, we suggest that the relatively lower fitness of ASV1 may be connected to the loss of the nitrous oxide reductase (nos) operon (and associated nitrous oxide reductase activity) due to the insertion at this genomic locus of a mobile genetic element carrying copper resistance genes. This study demonstrates the value of integrating genomic, environmental, and phenotypic data to characterize the biogeography of key microorganisms in contaminated sites.

microbiology↗

KR158 spheres harboring slow-cycling cells recapitulate GBM features in an immunocompetent system

Glioblastoma (GBM) poses a significant challenge in clinical oncology due to its aggressive nature, heterogeneity, and resistance to therapies. Cancer stem cells (CSCs) play a critical role in GBM, particularly in treatment-resistance and tumor relapse, emphasizing the need to comprehend the mechanisms regulating these cells. Also, their multifaceted contributions to the tumor-microenvironment (TME) underline their significance, driven by their unique properties. This study aimed to characterize glioblastoma stem cells (GSCs), specifically slow-cycling cells (SCCs), in an immunocompetent murine GBM model to explore their similarities with their human counterparts. Using the KR158 mouse model, we confirmed that SCCs isolated from this model exhibited key traits and functional properties akin to human SCCs. KR158 murine SCCs, expanded in the gliomasphere assay, demonstrated sphere forming ability, self-renewing capacity, positive tumorigenicity, enhanced stemness and resistance to chemotherapy. Together, our findings validate the KR158 murine model as a framework to investigate GSCs and SCCs in GBM-pathology, and explore specifically the SCC-immune system communications, understand their role in disease progression, and evaluate the effect of therapeutic strategies targeting these specific connections.

cancer biology↗

Defining cell type-specific immune responses in a mouse model of allergic contact dermatitis by single-cell transcriptomics

Allergic contact dermatitis (ACD), a prevalent inflammatory skin disease, is elicited upon repeated skin contact with protein-reactive chemicals through a complex and poorly characterized cellular network between immune cells and skin resident cells. Here, single-cell transcriptomic analysis of the murine hapten-elicited model of ACD reveals that upon elicitation of ACD, infiltrated CD4+ or CD8+ lymphocytes were primarily the IFN{gamma}-producing type 1 central memory phenotype. In contrast, type 2 cytokines (IL4 and IL13) were dominantly expressed by basophils, IL17A was primarily expressed by {delta}{gamma} T cells, and IL1{beta} was identified as the primary cytokine expressed by activated neutrophils/monocytes and macrophages. Furthermore, analysis of skin resident cells identified a sub-cluster of dermal fibroblasts with preadipocyte signature as a prominent target for IFN{gamma}+ lymphocytes and dermal source for key T cell chemokines CXCL9/10. IFN{gamma} treatment shifted dermal fibroblasts from collagen-producing to CXCL9/10-producing, which promoted T cell polarization toward the type-1 phenotype through a CXCR3-dependent mechanism. Furthermore, targeted deletion of Ifngr1 in dermal fibroblasts in mice reduced Cxcl9/10 expression, dermal infiltration of CD8+ T cell, and alleviated ACD inflammation in mice. Finally, we showed that IFN{gamma}+ CD8+ T cells and CXCL10-producing dermal fibroblasts co-enriched in the dermis of human ACD skin. Together, our results define the cell type-specific immune responses in ACD, and recognize an indispensable role of dermal fibroblasts in shaping the development of type-1 skin inflammation through the IFNGR-CXCR3 signaling circuit during ACD pathogenesis.

immunology↗

Architecture of genome-wide transcriptional regulatory network reveals dynamic functions and evolutionary trajectories in Pseudomonas syringae

The model Gram-negative plant pathogen Pseudomonas syringae utilises hundreds of transcription factors (TFs) to regulate its functional processes, including virulence and metabolic pathways that control its ability to infect host plants. Although the molecular mechanisms of regulators have been studied for decades, a comprehensive understanding of genome-wide TFs in Psph 1448A remains limited. Here, we investigated the binding characteristics of 170 of 301 annotated TFs through ChIP-seq. Fifty-four TFs, 62 TFs and 147 TFs were identified in top-level, middle-level and bottom-level, reflecting multiple higher-order network structures and direction of information-flow. More than forty thousand TF-pairs were classified into 13 three-node submodules which revealed the regulatory diversity of TFs in Psph 1448A regulatory network. We found that bottom-level TFs performed high co-associated scores to their target genes. Functional categories of TFs at three levels encompassed various regulatory pathways. Three and 25 master TFs were identified to involve in virulence and metabolic regulation, respectively. Evolutionary analysis and topological modularity network revealed functional variability and various conservation of TFs in P. syringae (Psph 1448A, Pst DC3000, Pss B728a and Psa C48). Overall, our findings demonstrated the global transcriptional regulatory network of genome-wide TFs in Psph 1448A. This knowledge can advance the development of effective treatment and prevention strategies for related infectious diseases.

microbiology↗

Coordinated molecular and ecological adaptations underlie a highly successful parasitoid

The success of an organism depends on the molecular and ecological adaptations that promote its beneficial fitness. Parasitoids are valuable biocontrol agents for successfully managing agricultural pests, and they have evolved diversified strategies to adapt to both the physiological condition of hosts and the competition of other parasitoids. Here, we deconstructed the parasitic strategies in a highly successful parasitoid, Trichopria drosophilae, which parasitizes a broad range of Drosophila hosts, including the globally invasive species D. suzukii. We found that T. drosophilae had developed specialized venom proteins that arrest host development to obtain more nutrients via secreting tissue inhibitors of metalloproteinases (TIMPs), as well as a unique type of cell-- teratocytes--that digest host tissues for feeding by releasing trypsin proteins. In addition to the molecular adaptations that optimize nutritional uptake, this pupal parasitoid has evolved ecologically adaptive strategies including the conditional tolerance of intraspecific competition to enhance parasitic success in older hosts and the obligate avoidance of interspecific competition with larval parasitoids. Our study not only demystifies how parasitoids weaponize themselves to colonize formidable hosts but also provided empirical evidence of the intricate coordination between the molecular and ecological adaptations that drive evolutionary success.

ecology↗

In vitro determination of osteo-adipogenic lineage choice of bone marrow stromal/stem cells (BMSCs)

Bone marrow stromal/stem cells (BMSCs) are primitive and heterogeneous cells that can be differentiated into osteoblasts, adipocytes and other subsets. Their bone-fat lineage commitment is responsible for the homeostasis of bone marrow microenvironment. However, there are little effective methods and evidence to simultaneously evaluate the lineage commitment of BMSCs. Here we provide a mixed osteo-adipogenic (OA) differentiation medium that could enable BMSCs differentiation into osteoblasts and adipocytes in vitro, and establish a method for simultaneous assessment of bone-fat lineage allocation of BMSCs based on the Alizarin red S and Oil red O staining, which have been used for detection of specific mineralized nodules and lipid droplets, respectively. This assay provides a specifically simple but effective and low-cost method to visualize the osteogenesis and adipogenesis of BMSCs, and evaluate the differentiation efficiency of lineage allocation of BMSCs.

cell biology↗