The PIWI-interacting RNA (piRNA) biosynthesis pathway is best studied for its role in suppressing Drosophila germline transposable elements. Piwi, the founding member of the pathway, is involved in adult intestinal stem cell (ISC) homeostasis. Whether a broader role of the PIWI pathway exists in the intestine remains unknown. Here, we characterize a role of the PIWI family protein Aubergine (Aub) in ISCs. While dispensable for basal ISC self-renewal, upregulation of Aub by damage-induced reactive oxygen species drives regenerative ISC proliferation through increased protein synthesis, including translation of ISC factors Myc and Sox21a. Unexpectedly, such roles of Aub in ISCs appear uncoupled from its piRNA regulatory function. Additionally, Aub and mammalian PIWIL1 mediate tumorigenic intestinal growth in Drosophila and human organoids, respectively. Our results reveal regulated protein translation as a fundamental aspect of regenerative ISC function and discover a central role of Aub in such process.

The adult B cell pool is a mosaic comprising short-lived naive B cells and long-lived memory. Using genetic time stamping, we have previously shown that early-life-origin (ELO) B cells contribute substantially to the adult mouse immune system. Here, we show that they share a memory-like signature, with ELO B-1 cells being enriched for the PD-L2/CD80 double-positive (DP) immunophenotype. Indeed, microbial antigen exposure in neonates expands distinct specificities within the DP B-1 cell compartment, identifying it as a reservoir of immunoglobulin (Ig)M memory. B cell chronic lymphocytic leukemia (CLL) is a disease marked by the accumulation of memory-like cells. By applying time stamping to a mouse model of unmutated CLL, we demonstrate that leukemic expansion is driven by B-1 clones that arise prior to postnatal day 10. Importantly, B-1 cells in mice and humans share molecular features with unmutated CLL, altogether supporting a potential contribution of ELO B cells to this disease.

The number of pet dogs is increasing, and the number of working dogs (e.g., guide dogs, police dogs) is also gradually increasing. Skin wounds are a common clinical problem in dogs and tend to be more common in the clinic as mechanical wounds. The healing process of skin wounds is often influenced by a variety of factors, including infection, nutritional status, and immune response, while wound healing is more difficult in dogs with diabetes or aging dogs. Mesenchymal stem cells (MSCs) play an important role in skin healing and regeneration with their multidirectional differentiation potential and immunomodulatory function. However, the application of MSCs alone for the treatment of skin wounds may have certain limitations, such as low cell survival and a lack of localization. Therefore, it is important to find methods that can enhance the therapeutic effect of MSCs. Secreted protein acidic and rich in cysteine (SPARC), an extracellular matrix protein widely involved in regulating biological processes such as cell proliferation, migration, and matrix production, may enhance the efficacy of MSCs in skin wound healing. This study aims to systematically evaluate the therapeutic efficacy of SPARC-overexpressing adipose-derived mesenchymal stem cells (ADSCs) in promoting skin wound healing by establishing wound models in normal, diabetic, and aged mice and dogs, thereby validating their potential under diverse physiological and pathological conditions. For in vitro validation, we used hydrogen peroxide (H2O2) to induce Human Umbilical Vein Endothelial Cell (HUVEC) and Human Keratinocyte Cell (HaCaT) injury. All animals were randomly assigned to six experimental groups as follows: (1) Model group: Untreated wound (negative control); (2) HY group: Hydrogel alone (vehicle control); (3) Con group: Control-ADSCs (cell control); (4) Con-Exo&HY group: Control-ADSC exosomes in hydrogel; (5) SPARC group: oe-SPARC-ADSCs (treatment); (6) SPARC-Exo&HY group: oe-SPARC-ADSC exosomes in hydrogel (treatment). Separately, HUVEC and HaCaT cells were assigned to four experimental conditions: a blank control group, a model group, a control-ADSC-treated group, and an oe-SPARC-ADSC-treated group. ADSCs modified by SPARC significantly promoted re-epithelialization integrity, collagen deposition, inflammation reduction, angiogenesis, and hair follicle regeneration during wound healing in dog skin. HUVEC and HaCaT cells proliferated after adding oe-SPARC-ADSCs cell supernatant. Meanwhile, quantitative proteomic sequencing data analysis showed that SPARC could promote skin wound healing by enhancing cell adhesion, hyaluronic acid binding, and vascular smooth muscle contraction of ADSCs. Both in vitro cellular assays and in vivo wound-healing models suggest that the combination of SPARC and ADSCs for the treatment of skin wounds has broad application prospects.

Intervertebral disk pathology, including disk herniation and degeneration, is a major contributor to chronic low back pain, and when conservative treatment fails, surgical management often involves discectomy-based procedures that leave residual annulus fibrosus (AF) defects associated with reherniation and progressive degeneration. These limitations have motivated interest in regenerative strategies using biomaterial scaffolds; however, reproducing the hierarchical, angle-ply architecture of the AF remains challenging. Here, we present a single-step extrusion-based 3D-printing approach to fabricate polycaprolactone (PCL) scaffolds with aligned microscale surface grooves that promote AF-like organization. Patterned nozzles with circumferential peaks generated uniaxial concave microgrooves (10-17 µm wide) directly during printing, enabling formation of multilamellar angle-ply constructs. Human bone marrow-derived mesenchymal stem cells cultured on patterned scaffolds aligned longitudinally within concave grooves, forming end-to-end arrays that guided extracellular matrix deposition. Gene expression analysis showed that topographical cues governed cellular organization without significantly altering gene expression profiles, while TGF-β3 supplementation upregulated outer AF-associated markers, including COL1, COL12, SFRP2, MKX, MCAM, and SCX. TAGLN expression increased specifically on patterned scaffolds in the absence of TGF-β3, indicating an association between microgroove-guided cellular organization and TAGLN expression, warranting further investigation into potential tension-related mechanisms. This novel single-step extrusion-printing approach leverages custom nozzle geometry to impart concave microgrooves, facilitating scalable fabrication of multilamellar angle-ply scaffolds that induce aligned cellular organization and support potential applications in annulus fibrosus repair, as well as mechanobiological studies of anisotropic musculoskeletal tissues.

Stem cell heterogeneity represents a critical yet underexplored variable in laser-assisted regenerative strategies. While photobiomodulation has been shown to influence mesenchymal stem cell (MSC) behavior, it remains unclear whether stem cell maturation status modulates responsiveness to Er,Cr:YSGG irradiation. This study investigated the differential response of magnetically separated STRO-1+ and STRO-1- SHED subpopulations to low-power Er,Cr:YSGG laser stimulation (0.10 W and 0.25 W), focusing on viability, extracellular matrix production, and lineage commitment. STRO-1+ cells comprised 13.4% ± 1.2% of the total Stem Cells from Human Exfoliated Deciduous teeth (SHED) population. Laser exposure did not impair metabolic activity in either subpopulation. Collagen synthesis demonstrated a power- and time-dependent increase, with maximal enhancement observed in STRO-1+ cells at 0.25 W after 7 days. Laser irradiation selectively promoted osteogenic differentiation, as evidenced by increased alkaline phosphatase (ALP) expression at 0.10 W and enhanced mineral deposition, while chondrogenic potential remained unaffected and adipogenesis was reduced following 0.10 W exposure. These findings suggest that ALP expression is temporally and power-dependently modulated during osteogenic progression. Overall, Er,Cr:YSGG photobiomodulation does not uniformly affect heterogeneous SHED populations but modulates lineage allocation and extracellular matrix deposition in a maturation- and power-dependent manner. Integrating stem cell subpopulation selection with laser-based bioactivation may represent a strategy to refine regenerative endodontic and biomaterial-guided therapies.

Zirconium is a widely used material in the field of dentistry, employed for implants and their components as well as for the creation of crowns and veneers. Given that its biocompatibility has been studied and demonstrated in various fields of application, it is necessary to analyze how surface modification of this material influences its properties. The purpose of this study was to analyze the biocompatibility, initial adhesion (48 h), and morphology of periodontal ligament stem cells (PDLSCs) seeded on different zirconium surfaces treated with laser micropatterning, as well as plastic coverslips as a control. The Neubauer chamber was used to count the cells adhered to each of the sets, and confocal and scanning electron microscopy were employed to examine the adhesion and morphology of periodontal ligament stem cells on each of the zirconium surfaces studied. Results: Statistically significant differences were found in terms of primary cell adhesion, with sets 3 (grid topography) and 4 (channel topography) showing the most favorable characteristics for fibroblast adhesion. It was concluded that regular and moderately rough surfaces promoted better cell proliferation and development.

Achilles tendon rupture often leads to poor functional recovery due to limited self-healing, with mitochondrial dysfunction in tendon stromal cells (TSCs) being a key factor in disease progression. Here, we developed adipose-derived stromal cell (ADSC) membrane-coated mitochondria (Mito-NPs) to target this dysfunction and evaluate their therapeutic potential for tendon repair. Mito-NPs exhibited uniform size, stable surface charge, and effective membrane coating. In lipopolysaccharide-induced inflammatory TSCs, Mito-NPs enhanced oxidative phosphorylation, improved mitochondrial metabolic homeostasis, and reshaped gene expression profiles to normalize TSC functional phenotypes, including inflammation, migration, and collagen synthesis. When encapsulated in a reactive oxygen species (ROS)-responsive hydrogel (Mito-NPs@HG) and implanted into rat Achilles tendon injuries, Mito-NPs@HG improved gait function, decreased local inflammation, and promoted histological repair of damaged tendons by enhancing collagen organization and reducing inflammation. Our findings demonstrate that ADSC membrane-coated mitochondria effectively rescue TSC dysfunction and facilitate tendon regeneration, providing a promising translational strategy for treating tendon injuries.

Acute myeloid leukemia (AML) is a molecularly heterogeneous neoplasm of hematopoietic stem and progenitor cells. The advent of high-resolution genomic sequencing has uncovered several genetic drivers of AML which spurred a surge of therapies that target the disease at a mutational, clonal, or epigenetic level. Currently, the molecular profiling of AML patients before treatment is commonplace and crucial for ensuring that patients receive the most optimal therapy for any driver mutations they may have. Here, we detail the current targeted therapies available for AML: specifically, those targeting the BCL2 family (venetoclax), FLT3 (midostaurin, gilteritinib, quizartinib), IDH1/2 (enasidenib, ivosidenib), and MENIN (revumenib, ziftomenib). In addition, we outline potential mechanisms of resistance against these therapies, as well as efforts being taken to prevent or bypass them.

Malignant melanoma is skin cancer arising from genetically altered melanocytes. Recently, a complex relationship between melanoma and chronic inflammation has been highlighted, representing an excellent condition for tumor development. Microalgae have been shown to be a promising source of bioactive compounds for drug discovery. In this study, we investigated Halamphora sp. (BEA0050) to identify possible compounds with immunomodulatory activity. The most active fraction (fraction D) showed anti-inflammatory activity against human melanoma cancer cells (A2058) stimulated using lipopolysaccharide (LPS) to induce an inflammatory phenotype. Chemical profiling of the bioactive fraction using chromatography and high-resolution mass spectrometry (UHPLC-HR-MS) revealed hydroxypheophorbide a, a breakdown product of chlorophyll a. In order to investigate the mechanism of action, the TNF-α release was detected through ELISA sandwich assays in A2058 cells and through confocal microscopy in LPS-stimulated HaCaT cells. Gene expression of principal pro-inflammatory cytokines and pathways was detected through real-time PCR, which showed the down-regulation of the inflammatory pathway in LPS-induced A2058 and HaCaT cells treated with 12.5 µg/mL of fraction D. This study reports for the first time the anti-melanoma and anti-inflammatory activities of Halamphora sp., identifying protein mediators and highlighting its biotechnological potential.

Diagnostic evaluation and management of nontraumatic osteonecrosis of the femoral head (ONFH) vary substantially. This systematic review was conducted to inform development of the Association Research Circulation Osseous (ARCO) clinical practice guideline for diagnosis and treatment of ARCO stages I to III ONFH.

The development of inks with suitable rheological, physicochemical, mechanical, and biological properties is crucial for the successful fabrication of functional scaffolds via extrusion-based 3D printing. In this study, collagen/chitosan hydrogels with varying polymer ratios were developed and characterized to evaluate their printability and suitability for cartilage tissue engineering. Rheological analyses revealed that all samples exhibited shear-thinning behavior and solid-like viscoelasticity, with the formulation of an 80:20 COL/CHI ratio (20CHI) demonstrating optimal filament formation and dimensional stability. Physicochemical analyses confirmed the preservation of the collagen triple helix and the formation of hydrogen bonding between chitosan and collagen. 20CHI scaffolds showed swelling capacity and high cohesiveness. In vitro studies confirmed the cytocompatibility of the scaffolds with murine fibroblasts and the ability of the scaffolds to promote adhesion, proliferation, and extracellular matrix production of both chondrocytes and adipogenic mesenchymal stem cells (aMSCs). Quantification of sulfated glycosaminoglycan (sGAG) indicated sustained matrix deposition over 28 days, particularly by chondrocytes. These findings demonstrate that 20CHI hydrogel is a promising candidate for 3D printing of biomimetic scaffolds for cartilage regeneration.

The regeneration and repair of scarless skin tissue remain a significant challenge for full-thickness wounds. Traditional wound management approaches, particularly passive healing through scabbing and conventional mechanical debridement, are frequently associated with significant pain, high infection risks, and abnormal scar formation, often failing to support the regeneration of skin appendages like hair follicles. In recent years, collagen-based scaffolds have been widely adopted in tissue-engineered skin substitutes owing to their favorable biocompatibility. However, their simplistic, single-component architecture inherently lacks the dynamic, cell-instructive microenvironment found in native skin, which not only compromises the long-term survival and functional integration of seeded cells but also directly leads to insufficient reconstruction of the dermo-epidermal junction, thereby impairing skin barrier function and ultimately limiting overall regenerative efficacy. In this study, we propose a biomimetic multilayer composite scaffold system in which decellularized amniotic membrane matrix (AM) is combined with fibroblast-laden collagen gel (FCG) and seeded with epidermal stem cells (EpiSCs). This bionic skin (denoted as AM-FCG-EpiSCs) is designed to achieve hierarchical regeneration of full-thickness skin defects. Compared with injured skin treated with Moropicin ointment, the injured skin treated with AM-FCG-EpiSCs healed more quickly and regenerated appendages like hair follicles without scarring. The results show that the biomimetic structure of AM-FCG-EpiSCs can mediate dynamic cell-cell interactions and regulate the microenvironment. This breakthrough overcomes the dual challenges of scar suppression and functional restoration in full-thickness skin regeneration, offering an innovative solution for translational medicine.

R-loops, three-stranded nucleic acid structures formed by an RNA-DNA hybrid, have emerged as important regulators of transcription and genome stability. Although advances in high-throughput sequencing have revealed widespread R-loop landscapes, platform-specific biases hinder the identification of conserved R-loops in specific cell types. Mouse embryonic stem cells, which are transcriptionally active, provide an ideal system for investigating the potential roles of stable R-loops in RNA biology. Here, we integrated 13 independent R-loop profiling datasets from four experimental platforms to define 27,950 Common R-loop regions in mouse embryonic stem cells and characterized their chromatin environment and associated biological functions. Common R-loop regions were reproducibly detected across methods and were preferentially localized to promoter-proximal and genic regions enriched in CpG islands. Genes associated with Common R-loops were highly and stably expressed, showing strong functional enrichment in RNA metabolic processes such as mRNA processing, RNA splicing, and ribonucleoprotein complex biogenesis. Chromatin state analysis revealed that Common R-loops are enriched in transcriptionally active and regulatory contexts. Sequence feature analysis further identified GC skew as a prominent signature of Common R-loops, particularly within transcribed chromatin states. Transcription factor motif analyses have identified distinct regulatory environments in Common R-loop regions, including pluripotency-associated OCT4-SOX2-TCF-NANOG motifs in enhancers, CTCF motifs in open chromatin, and YY1 motifs in promoters. Together, this study provides the first integrated analysis of conserved R-loop regions in mouse embryonic stem cells, revealing their preferential localization at regulatory loci linked to RNA metabolism and highlighting R-loops as structural and functional nodes in RNA biology.

The endothelial protein C receptor (EPCR) is an important component of the protein C (PC) system, recognised for its diverse roles in blood coagulation, inflammation, and stem cell regulation. Wound healing is a complex physiological process that can be divided into four distinct but overlapping phases: haemostasis, inflammation, proliferation and remodelling. Recently, EPCR has emerged as a key regulator in wound repair and regeneration. During haemostasis, EPCR enhances the conversion of PC to its activated form (APC) to optimise local and systemic anticoagulation. In the inflammatory phase, EPCR modulates immune cell activity, inhibits inflammatory factors, and maintains tissue barrier integrity. As the process transitions to the proliferative phase, EPCR promotes endothelial and epithelial cell proliferation, migration, neovascularisation and re-epithelization, and mediates the expression of matrix metalloproteinases to facilitate tissue reconstruction. Finally, during the remodelling phase, EPCR exerts a potential antifibrotic effect by regulating fibroblast activation and collagen deposition via the Transforming growth factor (TGF)-β1/Smad3 pathway, ensuring functional repair. While therapeutic potential has been shown in animal models, translating EPCR-mediated therapies to clinical application faces many challenges, including wound heterogeneity, dosage control, targeted delivery, and potential bleeding risks. Studies have shown that local drug delivery strategies, non-anticoagulant APC variants, and individualised treatment based on EPCR expression will be the key directions for future development. Additionally, EPCR may serve as a potential biomarker for assessing wound severity and guiding personalised interventions.

Cellular therapy using human cardiac mesenchymal progenitor cells (hMPCs) for regenerative medicine is hindered by poor cell survival and senescence. Long non-coding RNAs (lncRNAs) are critical regulators of cellular processes, yet their role in cardiac aging remains underexplored. Here, lncRNA microarray profiling identified a novel lncRNA, XLOC_002543, upregulated in hMPCs preconditioned with cobalt protoporphyrin (CoPP), which was named CoPP-Induced and SFPQ-Associated RNA Transcript (CISAT) due to its interaction with splicing factor proline and glutamine rich (SFPQ), confirmed via RNA pull-down and immunoprecipitation. CISAT was the only highly expressed transcript among seven lnc-ANKMY1-5 variants in hMPCs, as shown by RT-PCR. Notably, CISAT expression decreased in aging/senescent hMPCs, correlating with elevated p16INK4A, a senescence marker. Overexpression of CISAT reduced p16INK4A levels; enhanced hMPC survival, proliferation, and migration; and increased antioxidant and anti-apoptotic protein expression, while CISAT knockdown reduced resistance to H2O2-induced oxidative stress. In vivo, intramyocardial transplantation of CISAT-overexpressed hMPCs in an immune-deficient murine myocardial infarction model reduced fibrosis, promoted angiogenesis, and preserved cardiac function. Mechanistically, CISAT interacts with SFPQ to regulate NRF2-mediated redox homeostasis and inhibits p38 MAPK phosphorylation, mitigating senescence and enhancing cell survival. These findings suggest that targeting CISAT to modulate redox signaling and p38 MAPK pathways in aging hMPCs could improve their therapeutic efficacy for myocardial repair in heart disease.

Blood platelets are derived from megakaryocytes with functions extending beyond hemostasis to inflammation, immunity, and cancer. Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders driven by somatic mutations affecting JAK-STAT signaling, leading to excessive myeloid proliferation. Thrombosis affects approximately one-fifth of patients at diagnosis and remains elevated throughout the disease course, while the paradoxical coexistence of bleeding further complicates clinical management. In addition, MPNs may progress to advanced disease stages, including bone marrow fibrosis and transformation to acute myeloid leukemia, leading to ineffective hematopoiesis, worsening symptom burden, and poor clinical outcomes. This review outlines how peripherally circulating platelets provide a unique window into MPN pathophysiology, with emphasis on their functional and molecular abnormalities. We summarize current understanding of platelet-mediated hemostatic imbalance across MPN subtypes. We discuss the potential of platelet transcriptomics and proteomics to reveal disease-specific signatures. We further highlight emerging platelet-associated candidates with potential utility as dynamic biomarkers for both the pathological marrow niche and thrombotic and bleeding risk. Together, these insights underscore the potential of platelet-based approaches to complement existing diagnostic and prognostic strategies in MPNs.

Lipid abnormalities have been observed in brain, cerebrospinal fluid (CSF), and blood in association with late-onset Alzheimer's disease (LOAD). It is unknown which of these abnormalities are precursors to LOAD and which are concomitants of illness or its treatment. Inherent abnormalities can be identified in induced pluripotent stem cell (iPSC)-derived brain cells. These cells lack markers associated with aging and environmental exposures. The iPSC lines of patients with LOAD or healthy individuals were differentiated to astrocytes. Astrocytes are crucial to neural activity and health, and altered astrocyte functions are associated with LOAD pathology. Lipidomics analyses were performed on whole-cell and mitochondria-enriched fractions. Large reductions in cholesterol esters (CEs) and imbalances in fatty acids (FAs) were observed in LOAD-associated cells or their mitochondria. There were only modest differences in other lipid classes, including membrane structural lipids. The findings identify abnormalities in CEs, as well as in FAs, as inherent abnormalities and likely precursors to LOAD. These differences implicate mechanisms contributing to disease pathogenesis. Further study may lead to early interventions to prevent or delay LOAD.

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable clinical success in B cell malignancies. However, its efficacy in solid tumors remains limited, in part due to suboptimal expansion, persistence, and restrained effector function. Strategies that promote durable CAR-T cell fitness are therefore required to overcome these barriers. In this study, we generated HER2-CAR-T cells targeting human breast cancer cells and evaluated the impact of different cytokine supplementation strategies on CAR-T cell phenotype and function. We analyzed gene expression patterns and performed repetitive tumor killing assays to assess the ability of CAR-T cells expanded with IL-2 + IL-7 + IL-15 compared with IL-2 alone to maintain proliferation and cytotoxic function across multiple rounds of tumor cell exposure. Compared with IL-2 alone, supplementation with IL-7 and IL-15 significantly enhanced CAR-T cell expansion, preserved stem cell-like features prior to antigen encounter, and promoted superior proliferative capacity. Moreover, CAR-T cells cultured with IL-7+15 or IL-2+7+15 maintained sustained cytotoxicity and exhibited increased antitumor cytokine production during repeated tumor challenges. Notably, IL-7 and IL-15 supplementation induced a CD57+ CAR-T cell population that, unlike the immunosenescent CD57+ cells reported previously, retained full proliferative and cytotoxic capacity, with CD57 expression being dynamically downregulated upon antigen stimulation. Collectively, these findings demonstrate that incorporation of IL-7 and IL-15 into CAR-T cell manufacturing protocols substantially improves expansion, persistence, and effector function, supporting their use as a strategy to enhance CAR-T cell performance against solid tumors.

Dogs represent a promising animal model for analyzing human neurodegenerative diseases, owing to their similarities to humans in nervous system architecture and behavioral phenotypes. Neural stem cells (NSCs) serve as a highly valuable in vitro experimental model for investigating neurogenesis, neurodegenerative disease pathogenesis, and neural molecular biology; however, studies on immortalized canine neural stem cell lines remain scarce. Herein, we successfully established an immortalized canine hippocampal neural stem cell line that can be continuously passaged in vitro via SV40 large T antigen (SV40LT) viral infection and subsequent cellular transformation. Both the immortalized NSCs and their normal parental counterparts differentiated into neuronal and glial lineages under induced differentiation conditions. Normal canine hippocampal NSCs can be passaged for no more than 10 generations, whereas the immortalized line can be passaged indefinitely while maintaining a normal karyotype. This immortalized canine hippocampal NSC line can act as a critical experimental tool for future research into neural differentiation mechanisms and stem cell-derived therapeutic strategies for neurological disorders in dogs.

Glioblastoma (GBM) is an aggressive human malignancy. Recent advances in GBM research have highlighted innovative therapeutic approaches, including the use of small molecules that eliminate GBM in mouse models. However, there are few reports on the restoration of lost neuronal functions in patients. Considering that GBM contains GBM-initiating cells (GICs) with characteristics of both cancer and neural stem cells, we investigated whether GICs could be redirected toward non-tumorigenic neurons to support the preservation of neural function in the brain with GBM. We demonstrated that the neuronal differentiation inducer Isoxazole 9 (ISX9) effectively induced GICs to differentiate into neurons, accompanied by significant changes in their gene expression profiles. The sequential application of ISX9 and the DHODH inhibitor brequinar (BRQ), which successfully eradicated undifferentiated GICs, not only promoted neuronal differentiation but also inhibited GIC tumorigenesis in the mouse brain, leading to prolonged survival and preservation of motor function in tumor-bearing mice. Furthermore, pathological analysis revealed that this combination not only reduced the size of GIC brain tumors but also facilitated the formation of synapse-like structural contacts between GIC-derived cells and host mouse neurons, suggesting remodeling of the tumor-neural interface within the tumor-developed area. Collectively, these findings suggest that the modulation of tumorigenic GIC differentiation may represent a strategy to preserve neural circuit integrity within the tumor-bearing brain.