Spatial fibroblast niches define Crohn’s fistulae
Publication Summary This study by McGregor et al. describes how researchers created a detailed spatial atlas of Crohn’s disease fistulae to understand their formation and persistence. Using spatial transcriptomics and single-cell sequencing on 68 fistula samples, they identified specialized “fistula-associated stromal” (FAS) fibroblasts arranged in concentric layers around fistula tracts, each with distinct functions from active remodeling to fibrosis. These FAS cells express developmental transcription factors like TWIST1 and PRRX1 that drive tissue invasion and abnormal tunnel formation. The study reveals that common molecular pathways underpin fistulae across different intestinal locations, and similar FAS-like cells appear at the base of ulcers in non-fistulating Crohn’s disease, suggesting these may be precursors to fistula formation. How was Levitation Technology Used in the Paper? The LeviCell 1.0 platform was used as an alternative method for live stromal cell enrichment (vs FACS) from intestinal tissue samples. It offered researchers several benefits over FACS: This citation demonstrates LeviCell’s utility in high-quality single-cell genomics workflows where preserving cell viability and reducing technical artifacts are critical for accurate transcriptional profiling.
Matrix metalloproteinases are hallmark early biomarkers and therapeutic targets in FSHD
Publication Summary This study by Jung et al. examines matrix metalloproteinases (MMPs) as biomarkers and therapeutic targets in facioscapulohumeral muscular dystrophy (FSHD). The researchers found that MMP expression strongly correlates with disease severity in FSHD patients and is elevated even in early, uninflamed muscle tissue. Using the iDUX4 mouse model of FSHD, they identified fibroadipogenic progenitors (FAPs) and macrophages as the primary sources of MMPs, particularly MMP2, MMP14, and MMP19, during muscle degeneration. Treatment with batimastat, a pan-MMP inhibitor, reduced inflammation, fibrosis, FAP infiltration, and macrophage accumulation while improving muscle structure in the mouse model. The findings suggest that MMPs drive muscle pathology in FSHD and that MMP inhibitors could serve as a DUX4-independent therapeutic approach to mitigate disease progression. How was Levitation Technology Used in the Paper? LeviCell EOS served as a critical sample cleanup step to ensure high-quality, viable cells were used for the downstream single-cell RNA sequencing analysis, which identified FAPs and macrophages as the primary sources of MMPs in FSHD muscle.
A single-cell and spatial wheat root atlas with cross species annotations delineates conserved tissue specific marker genes and regulators
Publication Summary This study by Ke et al. provides a comprehensive single-cell RNA sequencing (scRNA-seq) atlas of soil-grown wheat root apical meristems, addressing the challenge of accurate cell type annotation in less-studied crop species. The researchers developed an orthology-based annotation pipeline that transfers cell type identities from well-characterized datasets in wheat, rice, maize, and Arabidopsis to their newly generated wheat dataset. They validated their computational predictions using untargeted spatial transcriptomics (STOmics Stereo-seq), confirming the accuracy of their annotation approach. Through cross-species comparative analysis, they identified evolutionarily conserved tissue-specific marker genes and generated cell type-specific gene regulatory networks for wheat and other species. This resource provides both known and previously uncharacterized cell type-specific marker genes and developmental regulators that will facilitate future single-cell studies in wheat and other non-model plant species. How LeviCell technology was used: LevitasBio’s Levitation Technology was used as a gentle cell enrichment and debris removal step during the protoplast preparation process for scRNA-seq. Specifically, after enzymatically digesting the wheat root tissues into protoplasts, the researchers used the LeviCell 1.0 magnetic levitation platform to enrich viable protoplasts and remove debris in a non-destructive manner. This was a critical quality control step that occurred before loading the cells onto the 10X Genomics Chromium platform for single-cell library preparation. The LeviCell system uses magnetic levitation technology to separate live cells from dead cells and debris based on their physical properties, without the harsh forces or labels that could damage sensitive plant protoplasts or alter gene expression. This gentle enrichment method helped ensure high-quality single cells for downstream scRNA-seq analysis.
Border-zone cardiomyocytes and macrophages regulate extracellular matrix remodeling to promote cardiomyocyte protrusion during cardiac regeneration
Florian Constanty and colleagues investigate the involvement of border-zone cardiomyocytes and macrophages in the remodeling of the extracellular matrix (ECM) to facilitate cardiomyocyte invasion during cardiac regeneration in zebrafish. The study reveals that these border-zone cardiomyocytes and macrophages actively contribute to modifying the ECM environment, which promotes the invasion of neighboring cardiomyocytes. This process is essential for efficient cardiac regeneration in zebrafish, shedding light on the intricate cellular interactions involved in tissue repair and regeneration in the heart.
Dual and spatially resolved drought responses in the Arabidopsis leafmesophyll revealed by single-cell transcriptomics
Drought stress imposes severe challenges on agriculture by impacting crop performance. Understanding drought responses in plants at a cellular level is a crucial first step towards engineering improved drought resilience. However, the molecular responses to drought are complex as they depend on multiple factors including the severity of drought, the profiled organ, its developmental stage or even the cell types therein.
Antigen presentation plays positive roles in the regenerative response to cardiac injury in zebrafish
Cardiera-da-Silva et al. investigate the role of antigen presentation in the process of heart regeneration in zebrafish, as this species possesses a remarkable ability to regenerate cardiac tissue after injury. The research found that antigen presentation, a process typically associated with the immune system’s response to pathogens, also supports heart tissue regeneration following injury. The findings suggest that antigen-presenting cells contribute to the regeneration of cardiac tissue, and offer insight into potential therapeutic approaches in humans.
Altered microbial bile acid metabolism exacerbates T cell-driven inflammation during GVHD
Sarah Lindner, PhD, and colleagues investigate the relationship between microbial transformation of bile acids, intestinal immune homeostasis, and inflammatory pathologies. By using a model of graft-versus-host disease (GVHD), the authors were able to determine that T cell-driven inflammation decreased the abundance of microbe-derived metabolites, which are important in reducing T cell-mediated disease.
TNFR1-mediated senescence and lack of TNFR2-signaling limit human intervertebral disc cell repair potential in degenerative conditions
Jennifer Gansau and colleagues investigate what factors contribute to the degeneration of Intervertebral discs (IVD), a condition that can lead to herniation and back pain due to the poor IVD healing capacities. The authors are able to identify distinct roles of TNFα-receptors (TNFRs) in IVD cell responses, particularly macrophages, to back pain conditions as key factors in poor IVD healing responses. The research indicates that IVD cells from back pain subjects demonstrate senescence, a state of irreversible cell cycle arrest, primarily mediated by TNFR1 signaling. This suggests a potential mechanism contributing to the degenerative processes observed in intervertebral discs associated with back pain.
The chromatin landscape of healthy and injured cell types in the human kidney
Debora Gisch, PhD, and colleagues pioneered a comprehensive epigenomic atlas of the kidney, shedding light on its cellular response to injury and repair. Utilizing the LeviCell® systems for a select number of samples, they purified nuclei from precious kidney biopsy samples and healthy tissue, ensuring high-quality inputs for subsequent single nuclei RNA-seq and ATAC-seq analyses, elucidating the chromatin landscape in kidney reference and adaptive injury states.
Venetoclax and dinaciclib elicit synergistic preclinical efficacy against hypodiploid acute lymphoblastic leukemia
Through a high-throughput screen using engineered NALM-16 cells, Holly Pariury, DO, and colleagues discovered that dinaciclib enhances the anti-leukemic effect of venetoclax against hypodiploid Acute Lymphoblastic Leukemia (ALL), an aggressive blood cancer disease with poor prognosis. After lentiviral transduction of the cells, Levitation Technology™ was utilized to improve cell suspension quality by removing dead cells and debris generated from the process. The results obtained offer insights into the CDK9/MCL-1 pathway’s central role in hypodiploid ALL and a promising new treatment approach for this aggressive cancer.