SEARCH · Search PubMed

Results for “Cellular Microenvironment”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,513 records · Page 84Linked to original sources

PubMed2005

Blood-on-a-chip.

Accurate, fast, and affordable analysis of the cellular component of blood is of prime interest for medicine and research. Yet, most often sample preparation procedures for blood analysis involve handling steps prone to introducing artifacts, whereas analysis methods commonly require skilled technicians and well-equipped, expensive laboratories. Developing more gentle protocols and affordable instruments for specific blood analysis tasks is becoming possible through the recent progress in the area of microfluidics and lab-on-a-chip-type devices. Precise control over the cell microenvironment during separation procedures and the ability to scale down the analysis to very small volumes of blood are among the most attractive capabilities of the new approaches. Here we review some of the emerging principles for manipulating blood cells at microscale and promising high-throughput approaches to blood cell separation using microdevices. Examples of specific single-purpose devices are described together with integration strategies for blood cell separation and analysis modules.

Animals↗

PubMed2001

Innovative techniques for harmful algal toxin analysis.

The global increase in frequency and intensity of harmful algal blooms (HABs) has led to more frequent incidence of seafood-borne illnesses and adverse impacts on natural resources. In response, public health agencies worldwide have mobilized to initiate HAB monitoring programs. To meet this demand, innovative analytical techniques are being developed that provide rapid and reliable detection of the causative organisms and the toxins produced. Modifications to conventional chromatography and mass spectrometry have greatly improved sensitivity and selectivity of these methods toward naturally occurring phycotoxins. Bioassay techniques using live organisms are giving way to molecular and cellular methods that measure the toxicologically significant activity of the toxin molecules. Molecular probes are being applied to distinguish species-specific RNA and DNA sequences for rapid identification of HAB-causing organisms. The direction of this new technology is to develop rapid and reliable screening methods for phycotoxins and the causative organisms to provide protection for public health, aquaculture, and natural resources. New methods also are being developed for detecting minute amounts of toxin molecules in microenvironments, leading to understanding the toxicokinetics and toxicological functions of the toxins.

Animals↗

PubMed2006

Costimulation requirements for antiviral CD8+ T cells differ for acute and persistent phases of polyoma virus infection.

The requirement for costimulation in antiviral CD8+ T cell responses has been actively investigated for acutely resolved viral infections, but it is less defined for CD8+ T cell responses to persistent virus infection. Using mouse polyoma virus (PyV) as a model of low-level persistent virus infection, we asked whether blockade of the CD40 ligand (CD40L) and CD28 costimulatory pathways impacts the magnitude and function of the PyV-specific CD8+ T response, as well as the humoral response and viral control during acute and persistent phases of infection. Costimulation blockade or gene knockout of either CD28 or CD40L substantially dampened the magnitude of the acute CD8+ T cell response; simultaneous CD28 and CD40L blockade severely depressed the acute T cell response, altered the cell surface phenotype of PyV-specific CD8+ T cells, decreased PyV VP1-specific serum IgG titers, and resulted in an increase in viral DNA levels in multiple organs. CD28 and CD40L costimulation blockade during acute infection also diminished the memory PyV-specific CD8+ T cell response and serum IgG titer, but control of viral persistence varied between mouse strains and among organs. Interestingly, we found that CD28 and CD40L costimulation is dispensable for generating and/or maintaining PyV-specific CD8+ T cells during persistent infection; however, blockade of CD27 and CD28 costimulation in persistently infected mice caused a reduction in PyV-specific CD8+ T cells. Taken together, these data indicate that CD8+ T cells primed within the distinct microenvironments of acute vs persistent virus infection differ in their costimulation requirements.

Acute Disease↗

PubMed1990

Kinetics of thymocyte regeneration in adult adriamycin treated rats: evidence for an exclusive role of bone marrow derived cells.

This paper describes a new, less toxic and more selective approach to study the adult thymus. An adriamycin (ADR), sparing bone marrow (BM) stem cells and nontoxic to cells that are not in cycle during treatment, was used as a depleting agent in conjunction with vascular thymus transplantation. We were able to deplete the thymus of thymocytes without damaging its microenvironment as witnessed by intact antigen profiles of stromal cells. Two models were used in this study, (1) regeneration after ADR induced depletion with or without BM reconstitution either systemically or intrathymically and (2) thymocyte turnover or regeneration in vascularly transplanted thymi. In the latter model either normal thymus was grafted into ADR treated recipient or ADR depleted thymus was grafted into normal recipient. These experiments clearly show that intact BM function is a prerequisite for intact continued cellularity of the adult thymus. Although the resident thymocyte population possesses some limited proliferating potential, it clearly does not seem to have a permanent self-renewing capacity of intrathymic stem cells.

Animals↗

PubMed2026

A pan-cancer single-cell atlas uncovers the role of sex hormones and chromosomes in sex-divergent reprogramming of the tumor microenvironment.

BACKGROUND: Sex bias is pervasive in tumors; however, how sex chromosomes and hormone-responsive signaling shape the tumor microenvironment (TME) remains insufficiently characterized. Considering the critical impact of the TME on tumor progression and response to immunotherapy, a pan-cancer investigation of sex-specific and cancer-context-dependent TME features is warranted. METHOD: Based on stringent inclusion criteria, we constructed a high-resolution pan-cancer single-cell sequencing atlas by integrating 31 publicly available single-cell RNA-seq datasets, comprising a total of 1,831,436 cells by integrating 468 samples from eight types of non-sex-specific solid tumors (282 males and 186 females). After correcting for batch effects, we identified major and minor cellular subsets. Multiple computational approaches were applied to investigate sex-associated differences in cellular composition, gene expression, pathway activity, malignant cell states and intercellular communication. RESULTS: We systematically compared sex-specific TME features across eight common solid malignancies. Male-biased CD8+ T cell exhaustion emerged as a recurrent but non-uniform feature, with its magnitude varying across cancer types and being modified by tissue-specific contexts. This pattern was associated with androgen-response signature scores and expression-based loss of the Y chromosome (LOY) scores. M2-like macrophage polarization showed a more cancer-type-dependent pattern; although female-biased enrichment was observed in selected malignancies, it did not represent a uniform pan-cancer feature. Expression-based X chromosome inactivation (XCI)/XCI escape-related programs, estrogen-response signature scores and stromal components, including fibroblasts and endothelial cells, were associated with macrophage and immune-regulatory states in specific tumor contexts. Tumor cells of male origin displayed higher genomic instability and more aggressive phenotypes, with androgen-response signatures and LOY contributing to the development of a male biased malignant state. Furthermore, expression-based LOY scores in malignant cells were associated with CD8+ T cell exhaustion based on transcriptomic proxies. CONCLUSION: Our study uncovers extensive but heterogeneous sex-specific differences in the TME across multiple cancer types. We propose a regulatory framework linking sex chromosomes, hormone-responsive signaling and TME interactions, which is consistent with recurrent male-biased CD8⁺ T cell exhaustion and context-dependent M2-like macrophage polarization. Importantly, the magnitude and, in some cancers, the direction of these sex-biased features are modified by tissue-specific contexts. These findings underscore the need to include sex chromosome and hormone status as essential biological variables in studies of the tumor microenvironment and the design of immunotherapies.

Tumor Microenvironment↗

PubMed2003

Multiple myeloma biology: lessons from the 5TMM models.

Multiple myeloma (MM) is a B cell neoplasm characterized by the monoclonal proliferation of plasma cells in the bone marrow, the development of osteolytic lesions and the induction of angiogenesis. These different processes require three-dimensional interactions, with both humoral and cellular contacts. The 5TMM models are suitable models to study these interactions. These murine models originate from spontaneously developed myeloma in elderly mice, which are propagated by in vivo transfer of the myeloma cells into young syngeneic mice. In this review we report on studies performed in the 5TMM models with special emphasis on the homing of the myeloma cells, the characterization of the migrating and proliferating clone and the identification of the isotype switch variants. The bone marrow microenvironment was further targeted with osteoprotegerin (OPG) to block the RANK/RANKL/OPG system and with potent bisphosphonates. Both treatments resulted in a significant protection against myeloma-associated bone disease, and they decreased myeloma disease, as evidenced by a lower tumor load and an increased survival of the mice. These different studies demonstrate the strength of these models, not only in unraveling basic biological processes but also in the testing of potentially new therapeutic targets.

Animals↗

PubMed1998

Substance P enhances cytokine-induced vascular cell adhesion molecule-1 (VCAM-1) expression on cultured rheumatoid fibroblast-like synoviocytes.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of the synovial membrane of multiple joints. This inflammatory microenvironment allows fibroblast-like synoviocytes (FLS) to express or enhance several adhesion or costimulatory molecules. This phenotypic shift, under proinflammatory cytokines, seems to be related to functional consequences for antigen presentation to T cells. The sensory neuropeptide substance P (SP), present at high levels, is able to act on FLS proliferation and enzyme secretion. These data led us to investigate whether SP could also provoke a phenotypic change of FLS. Using flow cytometry and a three-step cellular ELISA method, we determined whether SP has an influence on the expression of MHC class II, intercellular adhesion molecule-1 (ICAM-1), VCAM-1, LFA-3, CD40, B7.1 or B7.2 molecules on RA FLS incubated with interferon-gamma (IFN-gamma) or IL-1beta or tumour necrosis factor-alpha (TNF-alpha) with or without SP. Our results indicate that SP potentiates the effect of proinflammatory cytokines on the expression of VCAM-1 on RA FLS. We verified the presence of specific SP (NK1) receptor mRNA. Using reverse transcription-polymerase chain reaction, we showed that RA FLS of patients express NK1 receptor mRNA. These results suggest that SP increase of cytokine-induced VCAM-1 expression acts via this specific SP receptor. Thus, during chronic inflammation RA FLS are at the interface between the immune and the nervous systems.

Arthritis, Rheumatoid↗

PubMed2025

Proximity interactome of alphavirus replicase component nsP3 includes proviral host factors eIF4G and AHNAK.

All positive-strand RNA viruses replicate their genomes in association with modified intracellular membranes, inducing either membrane invaginations termed spherules, or double-membrane vesicles. Alphaviruses encode four non-structural proteins nsP1-nsP4, all of which are essential for RNA replication and spherule formation. To understand the host factors associated with the replication complex, we fused the efficient biotin ligase miniTurbo with Semliki Forest virus (SFV) nsP3, which is located on the cytoplasmic surface of the spherules. We characterized the proximal proteome of nsP3 in three cell lines, including cells unable to form stress granules, and identified >300 host proteins constituting the microenvironment of nsP3. These included all the nsPs, as well as several previously characterized nsP3 binding proteins. However, the majority of the identified interactors had no previously identified roles in alphavirus replication, including 39 of the top 50 interacting proteins. The most prominent biological processes involving the proximal proteins were nucleic acid metabolism, translational regulation, cytoskeletal rearrangement and membrane remodeling. siRNA silencing confirmed six novel proviral factors, USP10, AHNAK, eIF4G1, SH3GL1, XAB2 and ANKRD17, which are associated with distinct cellular functions. All of these except SH3GL1 were also important for the replication of chikungunya virus. We discovered that the small molecule 4E1RCat, which inhibits the interaction between the canonical translation initiation factors eIF4G and eIF4E, exhibits antiviral activity against SFV. Since the same molecule was previously found to inhibit coronaviruses, this suggest the possibility that translation initiation factors could be considered as targets for broadly acting antivirals.

Viral Nonstructural Proteins↗

PubMed1984

Ectopic mineralization in fibroblast cultures.

A human gingival fibroblast cell line was cultured in a DM-153 medium supplemented with 10% bovine serum. The cells in culture showed both intracellular and extracellular ectopic mineralization. Ultrastructurally, mineralization began within the round and irregularly shaped vesicles contained in large cytoplasmic vacuoles of fibroblasts. The first identifiable needle-shaped crystal was deposited on a point of the inner leaflet of the vesicle membrane. With the increase in size of the crystals, the membranous envelopes were gradually lost, and lattice planes (8.2 A) occurred within the crystal thickness. Crystals radiating from each mineralization center formed mineralized spherules in cytoplasmic vacuoles. The crystal clusters were extruded from the cells through membrane fusion or cellular degeneration in long-term cultures. These liberated clusters formed extracellular mineralizing matrices around the fibroblasts. In extracellular mineral deposition, the initial crystals arose within extracellular matrix vesicles, but were not associated with collagen, elastic fibers, and any other structures. These findings indicate that mineral accumulation and phase transformation of amorphous mineral to a crystalline form take place within the vesicular structures. This provides additional evidence for the view that the initiation of calcification and mineralization requires a microenvironment limited by a membranous (vesicular) structure derived from cells.

Adult↗

PubMed2005

Biomimetic delivery of keratinocyte growth factor upon cellular demand for accelerated wound healing in vitro and in vivo.

Exogenous keratinocyte growth factor (KGF) significantly enhances wound healing, but its use is hampered by a short biological half-life and lack of tissue selectivity. We used a biomimetic approach to achieve cell-controlled delivery of KGF by covalently attaching a fluorescent matrix-binding peptide that contained two domains: one recognized by factor XIII and the other by plasmin. Modified KGF was incorporated into the fibrin matrix at high concentration in a factor XIII-dependent manner. Cell-mediated activation of plasminogen to plasmin degraded the fibrin matrix and cleaved the peptides, releasing active KGF to the local microenvironment and enhancing epithelial cell proliferation and migration. To demonstrate in vivo effectiveness, we used a hybrid model of wound healing that involved transplanting human bioengineered skin onto athymic mice. At 6 weeks after grafting, the transplanted tissues underwent full thickness wounding and treatment with fibrin gels containing bound KGF. In contrast to topical KGF, fibrin-bound KGF persisted in the wounds for several days and was released gradually, resulting in significantly enhanced wound closure. A fibrinolytic inhibitor prevented this healing, indicating the requirement for cell-mediated fibrin degradation to release KGF. In conclusion, this biomimetic approach of localized, cell-controlled delivery of growth factors may accelerate healing of large full-thickness wounds and chronic wounds that are notoriously difficult to heal.

Animals↗

PubMed2006

Functional roles of immature dendritic cells in impaired immunity of solid tumour and their targeted strategies for provoking tumour immunity.

Dendritic cells play a crucial role in initiating tumour immunity as well as in the immune response for invading foreign pathogens such as bacteria and viruses. For bacterial and viral infections, the immature dendritic cells (iDCs) residing in peripheral tissues are efficiently activated and matured by pathogen signals for performing the immune response. In contrast, for self-antigens, the naive T cells are not activated by iDCs but proceed to anergy/deletion, and the generation of regulatory T cells for immune tolerance. The induction of immune response and tolerance is regulated strictly by iDCs as the sensor for homeostasis of immune response in the host. Despite the identification of some tumour antigens, tumour immunity is not provoked successfully. Even though there are some critical obstacles to inhibit effective tumour immunity, tumour cells are able to exploit the functional roles of iDCs for tumour progression, which are induced by tumour-derived soluble factors such as vascular endothelial growth factor (VEGF) and functionally modulated in the microenvironment. The iDCs still remain as the critical target for provoking tumour immunity. In this review, the functional roles of tumour-associated iDCs and the strategy for targeting iDCs in effective tumour immunity for the cancer patient are discussed.

Autoantigens↗

PubMed2006

Viral suppression and immune restoration in the gastrointestinal mucosa of human immunodeficiency virus type 1-infected patients initiating therapy during primary or chronic infection.

Although the gut-associated lymphoid tissue (GALT) is an important early site for human immunodeficiency virus (HIV) replication and severe CD4+ T-cell depletion, our understanding is limited about the restoration of the gut mucosal immune system during highly active antiretroviral therapy (HAART). We evaluated the kinetics of viral suppression, CD4+ T-cell restoration, gene expression, and HIV-specific CD8+ T-cell responses in longitudinal gastrointestinal biopsy and peripheral blood samples from patients initiating HAART during primary HIV infection (PHI) or chronic HIV infection (CHI) using flow cytometry, real-time PCR, and DNA microarray analysis. Viral suppression was more effective in GALT of PHI patients than CHI patients during HAART. Mucosal CD4+ T-cell restoration was delayed compared to peripheral blood and independent of the time of HAART initiation. Immunophenotypic analysis showed that repopulating mucosal CD4+ T cells were predominantly of a memory phenotype and expressed CD11 alpha, alpha(E)beta 7, CCR5, and CXCR4. Incomplete suppression of viral replication in GALT during HAART correlated with increased HIV-specific CD8+ T-cell responses. DNA microarray analysis revealed that genes involved in inflammation and cell activation were up regulated in patients who did not replenish mucosal CD4+ T cells efficiently, while expression of genes involved in growth and repair was increased in patients with efficient mucosal CD4+ T-cell restoration. Our findings suggest that the discordance in CD4+ T-cell restoration between GALT and peripheral blood during therapy can be attributed to the incomplete viral suppression and increased immune activation and inflammation that may prevent restoration of CD4+ T cells and the gut microenvironment.

Antiretroviral Therapy, Highly Active↗

PubMed2005

Gene expression patterns in human and mouse B cell development.

B lymphocytes develop in the mammalian bone marrow through a series of developmental stages that can be ordered by recombination status of the immunoglobulin genes. Recent studies have combined RNA amplification by in vitro transcription with high-density oligonucleotide array technology to generate gene expression profiles of ex vivo isolated B cell precursor stages from humans and mice. Cellular differentiation through five subsequent stages of mouse B cell development involves differential expression of 10.7% of the 13,104 genes analysed, while between 2.8% and 6.8% change upon differentiation from one stage to the next. Early precursors express primarily genes involved in general metabolic processes, while B cell-specific functions are acquired in more mature stages. In human B cell development, pre-BI and small pre-BII cells express genes necessary for interactions with the respective microenvironments, while cycling, large pre-BII cells have a more cell-autonomous expression pattern. A direct comparison between human and mouse B cell development is hampered by the limited number of homologues that can be identified by reciprocal basic local alignment search tool (BLAST) searches of non-redundant expressed sequence tags (EST) clusters or of the available genome sequences. However, genes for which homologues could be identified that are differentially expressed during B cell development of both human and mouse have very similar expression patterns in the two species, are often expressed in large pre-BII cells, and are involved in DNA replication and cell-cycle regulation. Many more genes with homologous sequences, however, are differentially expressed during B cell development of only one species, indicating that genes can be used in different functional contexts even when the sequence is conserved. This implies that care should be taken with the interpretation of gene expression data from model organisms.

Animals↗

PubMed2003

NVP-LAQ824 is a potent novel histone deacetylase inhibitor with significant activity against multiple myeloma.

Histone deacetylase (HDAC) inhibitors are emerging as a promising new treatment strategy in hematologic malignancies. Here we show that NVP-LAQ824, a novel hydroxamic acid derivative, induces apoptosis at physiologically achievable concentrations (median inhibitory concentration [IC50] of 100 nM at 24 hours) in multiple myeloma (MM) cell lines resistant to conventional therapies. MM.1S myeloma cell proliferation was also inhibited when cocultured with bone marrow stromal cells, demonstrating ability to overcome the stimulatory effects of the bone marrow microenvironment. Importantly, NVP-LAQ824 also inhibited patient MM cell growth in a dose- and time-dependent manner. NVP-LAQ824-induced apoptotic signaling includes up-regulation of p21, caspase cascade activation, and poly (adenosine diphosphate [ADP]) ribose (PARP) cleavage. Apoptosis was confirmed with cell cycle analysis and annexin-propidium iodide staining. Interestingly, treatment of MM cells with NVPLAQ824 also led to proteasome inhibition, as determined by reduced proteasome chymotrypsin-like activity and increased levels of cellular polyubiquitin conjugates. Finally, a study using NVP-LAQ824 in a preclinical murine myeloma model provides in vivo relevance to our in vitro studies. Taken together, these findings provide the framework for NVP-LAQ824 as a novel therapeutic in MM.

Acetylation↗

PubMed1998

Developmental and hormonal regulation of keratinocyte growth factor expression and action in the ovarian follicle.

The developing ovarian follicle is one of the most rapidly proliferating normal tissues in vivo. Mesenchymal-epithelial cell interactions between theca cells and granulosa cells are essential for this follicular expansion. Ovarian hormones (i.e. estrogen and LH) may promote follicular development by regulating the local production of mesenchymal inducer proteins that mediate theca cell-granulosa cell interactions. Recently, theca cells were shown to produce keratinocyte growth factor (KGF) that can act in a paracrine manner to stimulate granulosa cell growth. In this study, the developmental and hormonal regulation of KGF was examined during follicular development in the bovine ovary. Expression of KGF in theca cells and the KGF receptor (KGFR, or splice variant of the fibroblast growth factor family receptor family, FGFR-2) in granulosa cells was examined using RT-PCR. Both KGF and KGFR were detected throughout follicular development in small (<5 mm), medium (5-10 mm), and large (>10 mm) follicles. Quantitative RT-PCR assays were used to determine steady-state levels of KGF and KGFR messenger RNAs. Developmental regulation of KGF and KGFR was analyzed in freshly isolated theca cells and granulosa cells from small, medium, and large follicles. Observations demonstrated that expression of KGF (in theca cells) and KGFR (in granulosa cells) was highest in large follicles. These results suggest that KGF actions are important for the rapid proliferation of granulosa cells in large follicles. Estrogen and LH are the primary endocrine hormones that regulate theca cell function in vivo. Therefore, hormonal regulation of KGF was analyzed by treating serum-free theca cell cultures with estrogen and human CG (hCG, an LH agonist). Results showed that both estrogen and hCG stimulated KGF gene expression in theca cells. These results suggest that estrogen and LH may promote follicular growth (i.e. granulosa cell proliferation), in part, by stimulating the local production of KGF. Effects of KGF on granulosa cell differentiated functions were examined. Treatment with KGF reduced basal levels and FSH-stimulated levels of aromatase activity in bovine and rat granulosa cells. In addition, KGF inhibited the ability of hCG to stimulate progesterone production by granulosa cells. The inhibition of granulosa cell steroid production by KGF was likely the indirect effect of promoting cellular proliferation. Therefore, KGF directly stimulates granulosa cell proliferation and indirectly inhibits granulosa cell differentiated functions. Combined results suggest that theca cell production of KGF may be important for ovarian folliculogenesis. This is the first report of the regulation of KGF expression in the ovary. The developmental and hormonal regulation of KGF and KGFR during folliculogenesis provides evidence that KGF may be important for hormone-induced granulosa cell proliferation. As a result, KGF may be essential for establishing the microenvironment required for oocyte maturation in the ovary.

Animals↗

PubMed2004

Therapeutic efficacy of MUC1-specific cytotoxic T lymphocytes and CD137 co-stimulation in a spontaneous breast cancer model.

To study immunology in breast tumors, we have utilized a mammary gland adenocarcinoma model in which mice develop spontaneous tumors of the mammary gland which are initiated at puberty and express a human tumor antigen, MUC1. MUC1 (CD227) is over-expressed in 90% of human breast cancers and its glycosylation status and pattern of expression in cancer cells is altered. Humoral and cellular responses to MUC1 have been reported in breast cancer patients and therefore, MUC1 is being evaluated as a target for immune intervention. This mouse model of spontaneous breast cancer allows the evaluation of anti-MUC1 immune responses at all stages of the disease. In this report, we review the model as it pertains to a) the development of the tumor, b) MUC1 expression, and the native immune responses against MUC1 as tumors progress, and c) the immune suppressive microenvironment within the developing tumor. Finally, we report our latest findings describing the therapeutic efficacy of adoptively transferred MUC1-specific cytotoxic T lymphocytes (MUC1-CTL) in these mice and discuss ways to increase their effectiveness by agonistic monoclonal antibody against CD137 T cell costimulatory molecule.

Animals↗

PubMedDate not supplied

Intracranial neurothekeoma--a rare parenchymal nerve sheath myxoma of the middle cranial fossa.

Neurothekeomas are rare, benign nerve sheath tumors, usually arising from cutaneous nerves in the head and neck region. So far, only 4 cases of the intracranial counterpart have been reported and these were located in the posterior fossa, sellar and parasellar region. We report here the first case of neurothekeoma located deep inside the brain parenchyma. Histologically, the tumor had lobular appearance with bland morphology in spite of cellular pleomorphism, myxoid background and variable S-100 positivity, characteristics of neurothekeomas. The schwannian origin was further confirmed ultrastructurally by demonstrating basal lamina and Luse bodies. Because of its benign nature, the lesion does not need postoperative radiotherapy. Histogenesis of neurothekeoma arising in the parenchyma remains enigmatic. The probable cell of origin could be the Schwann cell or perineurial cell of the nerve twigs around the blood vessels or by extreme differentiation of the precursor cell resting in a suitable microenvironment to the schwannian phenotype.

Adolescent↗

PubMed2026

Accurately Deciphering Tissue Heterogeneity From Spatial Multi-Modal and Multi-Omics With STransformer.

Advances in spatially resolved technologies enable the simultaneous acquisition of diverse data modalities within a tissue slice while preserving critical spatial context, which presents unprecedented opportunities to decipher intricate tissue heterogeneity. However, existing computational approaches lack the intrinsic flexibility to universally process both spatial multi-modal and multi-omics data. Here, we introduce STransformer, a unified deep learning framework designed to seamlessly accommodate a comprehensive landscape of spatial data. By simultaneously capturing short-range cellular interactions and tissue-wide semantic patterns, it extracts robust representations to accurately dissect complex tissue heterogeneity. Systematic evaluations across diverse species, tissue types, and data modalities highlight its profound versatility. For spatial multi-modal data, STransformer delineates intricate anatomical structures in the human cortex, uncovers pathological mechanisms in Alzheimer's disease, and characterizes dynamic spatiotemporal developmental trajectories during chicken cardiogenesis. Scaling to spatial multi-omics data, STransformer synergizes spatial transcriptomic and proteomic profiles to decipher intricate immune microenvironments within the human tonsil, and jointly analyzes spatial epigenomic and transcriptomic data to infer regulatory mechanisms in the mouse embryonic brain. Consequently, STransformer serves as a highly versatile and robust analytical framework for advancing our understanding of tissue heterogeneity and disease pathogenesis.

Multiomics↗