Biology subjects

Min, B.

Publications and source records attributed to Min, B..

At least 19 recordsLinked to original sources

bioRxiv2026

Simultaneous multi-area recordings in macaque frontoparietal cortex during a manual object-interaction task

Dexterous hand control is essential for daily activities and a top restoration priority for people with tetraplegia, yet neurophysiological datasets suitable for studying and decoding naturalistic hand behavior remain scarce. Most available recordings constrain movements to a small number of degrees of freedom or cover only a single stereotypical grasp-and-hold structure. Moreover, previous brain-computer interface (BCI) studies have largely relied on signals from a single cortical area, even though dexterous hand control is distributed across an interconnected frontoparietal network. To address these limitations, we designed a paradigm that elicits rich hand movements across 40 distinct hand-object interaction conditions. We recorded simultaneous frontoparietal activity with hand kinematics from a rhesus macaque performing them. Neural activity was recorded from the primary motor cortex, anterior intraparietal area, and ventral premotor cortex using microelectrode arrays spanning 1,920 channels, while a multi-camera markerless motion-capture system acquired video from which kinematics were extracted offline. The dataset comprises data from 20 sessions, including processed neural features, synchronized 3D coordinates of hand and elbow keypoints, and trial-level metadata including task conditions and event timing. We further provide technical validation, including a neural decoding benchmark with multiple algorithms for continuous keypoint coordination reconstruction. We found that cross-day and cross-task decoding performance varied among algorithms. Variation in channel availability leads to different performance degradation curves in different algorithms. This task-rich dataset offers a valuable resource for investigating the neural mechanisms of dexterous hand control and for advancing the performance of motor BCIs.

neuroscience↗

bioRxiv2026

The Lag3 KIEELE motif couples HPK1 to metabolic and functional regulation of Foxp3+ regulatory T cells

Lymphocyte activation gene-3 (Lag3) is an inhibitory receptor that limits effector T cell activation and function. We previously demonstrated that Lag3 supports regulatory T (Treg) cell function through Myc-dependent metabolic reprogramming. However, the intracellular mechanisms underlying this regulation remain incompletely understood. Here, we generated mice with Treg-specific deletion of the Lag3 KIEELE motif and demonstrated that this motif is required for Treg-mediated suppression of autoimmune inflammation. Loss of the Lag3 KIEELE motif led to enhanced TCR/PI3K-Akt/MEK-ERK signaling and Myc expression, accompanied by increased glycolytic activity and acquisition of effector T cell-like features. We also identified that hematopoietic progenitor kinase 1 (HPK1) and Cbl-interacting protein of 85 kDa (CIN85) associate with Lag3 through the KIEELE motif. HPK1 depletion partially recapitulated the phenotypic changes and impaired Treg suppressive function in vivo. Together, these findings identify the KIEELE motif as a critical link between Lag3-associated signaling machinery and metabolic regulation that sustains Treg suppressive function during autoimmune inflammation.

immunology↗

bioRxiv2026

Metabolic disease-relevant stimuli unmask context-dependent genetic regulation of cardiometabolic loci in human adipocytes

Genome-wide association studies (GWAS) have identified thousands of loci associated with cardiometabolic disease, yet translating these associations into regulatory mechanisms, effector genes, and cellular programs remains a major challenge. A key limitation is that genetic effects are often highly context dependent, varying across cell states and environmental conditions that are difficult to model at scale. Here, we leverage CellGenBank, a population-scale biobank of primary human adipose-derived mesenchymal stem cells (AMSCs), to implement a multi-donor cell village in vitro system to map cardiometabolic disease genetic variation across adipocyte differentiation and metabolic stress conditions. We pooled AMSCs from 118 donors into multiplexed villages, differentiated them toward adipocytes, and profiled chromatin accessibility and gene expression using single-nucleus multiome sequencing under four disease-relevant conditions: basal, elevated free fatty acids, low glucose, and hypoxia. By combining with genetic demultiplexing, we quantify how regulatory element activity, gene expression, and higher-order cellular programs are modulated by both genotype and environmental context. Across conditions, we identify widespread context-specific cis-regulatory effects, including expression and chromatin accessibility quantitative trait loci that are masked in baseline states. Genetic effects frequently converge on coordinated transcriptional programs linked to lipid metabolism, insulin responsiveness, and stress adaptation, enabling the identification of cellular program QTLs that bridge variants, genes, and disease-relevant phenotypes. Integration with cardiometabolic GWAS reveals enhanced colocalization in condition- and state-resolved analyses, highlighting the importance of modeling environmental context to resolve disease mechanisms. Together, our study establishes large-scale adipocyte cell villages as a powerful and generalizable framework to map the context-dependent regulatory architecture of cardiometabolic disease and provides a resource linking human genetic variation to adipocyte cellular programs.

genomics↗

bioRxiv2026

Discovering Novel Circuit Mechanisms in Higher Cognition through Factor-Centric Recurrent Neural Network Modeling

Recurrent neural networks (RNNs) have transformed how systems neuroscientists generate hypotheses about circuit mechanisms in higher cognition. Yet their promise has been constrained by a fundamental limitation: conventional RNNs are neuron-centric and therefore often difficult to interpret mechanistically. Here we introduce Restricted-RNN, a factor-centric RNN modeling framework developed to uncover interpretable circuit mechanisms. By formalizing factor communication through subpopulations, the dual of neuron communication through subspaces, Restricted-RNN departs fundamentally from standard neuron-centric RNN models and provides a distinct framework for describing circuit mechanisms. Using this approach, we identify novel circuit mechanisms underlying sequence working memory control and the counterintuitive firing-rate reversal observed in perceptual decision-making, with key predictions supported by neurophysiological recordings from monkey frontal and parietal cortex. More importantly, factor-centric RNN modeling reveals a unified low-dimensional neural control state space that links seemingly disparate phenomena across tasks, providing a geometric framework for understanding the pervasive role of control in higher cognition.

neuroscience↗

bioRxiv2026

Opening the Black Box of Neural Computation from Neural Recordings with Gain-Modulated Linear Dynamical System

Inferring computational mechanisms from neural recordings is a central goal in systems neuro-science. Recent developments have identified low-rank recurrent neural networks (RNNs) as an effective tool for fitting observed neural activity and extracting neural dynamics. However, we show that accurate activity fitting alone does not guarantee mechanistic validity: even well-fitted low-rank RNNs can yield misleading circuit interpretations in the absence of ground-truth model settings on synthetic datasets. To address this limitation, we introduce a gain-modulated linear dynamical systems (gmLDS) method, which decomposes latent-variable interactions into a time-varying gain and static low-rank connectivity components. This decomposition captures linearized dynamics near neural trajectories and enables flexible adaptation to each neurons nonlinear responses without requiring a predefined activation function. Extensive validation across multiple synthetic datasets shows that gmLDS accurately reproduces neural activity, gain and connectivity, thereby capturing the fine structure of linearized dynamics and the underlying circuit mechanisms. When applying to neural recordings from a context-dependent decision-making task, gmLDS uncovers evidence for the coexistence of two prevalent selection mechanisms, offering new insights into a long-standing unresolved issue in the field. Together, our results establish gmLDS as a principled approach for opening the black box of neural computation from neural recordings.

neuroscience↗

bioRxiv2025

Targeting Impaired Type I Interferon IL-27 Signaling Rescues T Regulatory Cell Suppressive Function in Relapsing-Remitting Multiple Sclerosis

T Regulatory T cells (Tregs) from patients with relapsing-remitting multiple sclerosis (RRMS) exhibit impaired suppressive function, yet the underlying molecular mechanisms remain elusive. Single-cell RNA sequencing (scRNAseq) of ex vivo-sorted Tregs from RRMS patients and matched healthy controls (HCs) revealed down-regulation of type I IFN (IFN) and IL-27 signaling pathways in RRMS Tregs. These Tregs showed reduced expression of IFN-stimulated genes (ISGs) (ISG15, MX1, IFITM1, IFI44L, OAS1), as well as key mediators of Treg suppressive function (LGALS3, CD81, FCRL3, CD7, CSTB), all suggesting a key role of decreased IFN signaling in RRMS Treg dysfunction. To therapeutically target IFN signaling pathways and improve Treg suppressive functions, we used cGAMP-loaded microparticles (MPs) to activate the stimulator of IFN genes (STING) in experimental autoimmune encephalomyelitis (EAE). cGAMP-MP treatment ameliorated EAE via induction of Tregs expressing IL-27R, IL-10, TGF-b, and Granzyme B. This effect was abolished in Treg-specific IL-27R (Treg{Delta}Il27ra) knockout mice, confirming that IL-27 signaling is essential for Treg suppression. In vitro IL-27 stimulation of RRMS-derived Tregs restored expression of IFN pathway genes (IRF1, IFNGR, IFI16) and Treg suppressive genes (ICOS, IKZF3, IL7R, TIGIT). Thus, we propose that IL-27 pre-stimulation may restore their suppressive function and migration (via CCR6, CCR7, S100A11 and S1PR4) to the central nervous system (CNS) in future clinical trials. SignificanceSeveral studies have reported a role for type I IFN and IL-27 signaling in the induction of suppressive Tregs in autoimmune diseases. We report that RRMS Tregs have decreased expression of type I IFN and IL-27 signalling-related genes in comparison to HCs. The animal model of MS (EAE) was successfully treated with cGAMP-MPs, which, via induction of type I IFN, IL-27 and IL-10, restored Treg suppressive function. A scRNAseq study of Tregs from MS patients revealed that IL-27 in vitro stimulation normalized the expression of type I IFN genes and Treg suppressive genes. We propose that IL-27 pre-treatment may enhance Treg suppressive function and migration to the CNS in future clinical trials.

immunology↗

bioRxiv2025

Single Cell RNA-sequencing of BCG naive and recurrent non-muscle invasive bladder cancer reveals a CD6/ALCAM mediated immune-suppressive pathway

Non-muscle invasive bladder cancer (NMIBC) represents 70-80% patients with newly diagnosed bladder cancer, and Bacillus Calmette-Guerin (BCG) remains a cornerstone treatment for intermediate-and high-risk NMIBC to prevent disease recurrence and progression. However, many patients experience recurrence after induction BCG, posing significant challenges in the management of the disease. We conducted single cell RNA sequencing on freshly collected NMIBC samples, distinguishing between those naive to BCG treatment and those that recurred post-BCG treatment. We observed a clear activation of inflammatory pathways across cell types during recurrence, but these were not associated with canonical immune checkpoint or T cell exhaustion phenotypes. Analysis of cell-to-cell communication revealed enhanced interactions between T cells and urothelial cells in BCG-recurrence, predominantly modulated by CD6 and ALCAM. Furthermore, we found CD6hi T cells to be immunosuppressed and enriched in recurrent samples, suggesting a potential role for CD6 as an immune evasion signal in NMIBC. SIGNIFICANCEThese findings uncover a novel mechanism responsible for bladder cancer recurrence after BCG treatment. Enhanced T cell-urothelial cell communication in recurrent tumors mediated by CD6 and ALCAM leads to an immunosuppressed state. Thus, CD6 may have potential as a therapeutic target to augment BCG response in non-muscle invasive bladder cancer.

cancer biology↗

bioRxiv2025

IL-27 limits HSPC differentiation during infection and protects from stem cell exhaustion

Many inflammatory stimuli can induce progenitor cells in the bone marrow to produce increased numbers of myeloid cells as part of the process of emergency myelopoiesis. These events are associated with trained immunity and have long-term impacts on hematopoietic stem and progenitor cell (HSPC) development but can also compromise their function. While many cytokines support emergency myelopoiesis, less is known about the mechanisms that temper these events. When mice that lack the cytokine IL-27 were infected with Toxoplasma gondii, there was enhanced generation of monocyte progenitors and increased numbers of inflammatory monocytes. In the bone marrow of infected mice there was increased production of IL-27 that localized with HSPCs and a survey of cytokine receptor expression highlighted that HSPCs were uniquely poised to respond to IL-27. Furthermore, the use of in vitro differentiation assays and mixed bone marrow chimeras revealed that HSPCs from IL-27 deficient mice are pre-disposed towards the monocyte lineage. Additional studies highlighted that after infection loss of the IL-27R resulted in reduced HSPC fitness that manifested as reduced proliferative responses and a decreased ability to reconstitute the hematopoietic system. Thus, the ability of IL-27 to act on HSPC provides a regulatory brake on differentiation to limit monocyte induction and preserve HSPC stemness.

immunology↗

bioRxiv2024

A simple neural circuit model explains diverse types of integration kernels in perceptual decision-making

The ability to accumulate evidence over time for deliberate decision is essential for both humans and animals. Decades of decision-making research have documented various types of integration kernels that characterize how evidence is temporally weighted. While numerous normative models have been proposed to explain these kernels, there remains a gap in circuit models that account for the complexity and heterogeneity of single neuron activities. In this study, we sought to address this gap by using low-rank neural network modeling in the context of a perceptual decision-making task. Firstly, we demonstrated that even a simple rank-one neural network model yields diverse types of integration kernels observed in human data--including primacy, recency, and non-monotonic kernels--with a performance comparable to state-of-the-art normative models such as the drift diffusion model and the divisive normalization model. Moreover, going beyond the previous normative models, this model enabled us to gain insights at two levels. At the collective level, we derived a novel explicit mechanistic expression that explains how these kernels emerge from a neural circuit. At the single neuron level, this model exhibited heterogenous single neuron response kernels, resembling the diversity observed in neurophysiological recordings. In sum, we present a simple rank-one neural circuit that reproduces diverse types of integration kernels at the collective level while simultaneously capturing complexity of single neuron responses observed experimentally. Author SummaryThis study introduces a simple rank-one neural network model that replicates diverse integration kernels--such as primacy and recency--observed in human decision-making tasks. The model performs comparably to normative models like the drift diffusion model but offers novel insights by linking neural circuit dynamics to these kernels. Additionally, it captures the heterogeneity of single neuron responses, resembling diversity observed in experimental data. This work bridges the gap between decision-making models and the complexity of neural activity, offering a new perspective on how evidence is integrated in the brain.

neuroscience↗

bioRxiv2024

Elucidating the Selection Mechanisms in Context-Dependent Computation through Low-Rank Neural Network Modeling

Humans and animals exhibit a remarkable ability to selectively filter out irrelevant information based on context. However, the neural mechanisms underlying this context-dependent selection process remain elusive. Recently, the issue of discriminating between two prevalent selection mechanisms-- input modulation versus selection vector modulation--with neural activity data has been highlighted as one of the major challenges in the study of individual variability underlying context-dependent decision-making (CDM). Here, we investigated these selection mechanisms through low-rank neural network modeling of the CDM task. We first showed that only input modulation was allowed in rank-one neural networks and additional dimensions of network connectivity were required to endow neural networks with selection vector modulation. Through rigorous information flow analysis, we gained a mechanistic understanding of why additional dimensions are required for selection vector modulation and how additional dimensions specifically contribute to selection vector modulation. This new understanding then led to the identification of novel neural dynamical signatures for selection vector modulation at both single neuron and population levels. Together, our results provide a rigorous theoretical framework linking network connectivity, neural dynamics and selection mechanisms, paving the way towards elucidating the circuit mechanisms when studying individual variability in context-dependent computation.

neuroscience↗

bioRxiv2023

Genomic epidemiology and antifungal-resistant characterization of Candida auris, Colombia, 2016-2021

Since 2016 in Colombia, ongoing transmission of Candida auris has been reported in multiple cities. Here, we provide an updated description of C. auris genomic epidemiology and the dynamics of antifungal resistance in Colombia. We sequenced 99 isolates from C. auris cases with collection dates ranging from June 2016 to January 2021; the resulting sequences coupled with 103 previously generated sequences from C. auris cases were described in a phylogenetic analysis. All C. auris cases were of clade IV. Of the 182 isolates with antifungal susceptibility data, 67 (37%) were resistant to fluconazole, and 39 (21%) were resistant to amphotericin B. Isolates predominately clustered by country except for 16 isolates from Bogota, Colombia, which grouped with isolates from Venezuela. The largest cluster (N=166 isolates) contained two subgroups. The first subgroup contained 26 isolates, mainly from Cesar; of these 85% (N=22) were resistant to fluconazole. The second subgroup consisted of 47 isolates from the north coast; of these, 81% (N=38) were resistant to amphotericin B. Mutations in the ERG11 and TAC1B genes were identified in fluconazole-resistant isolates, and two amino acid substitutions in PSK76257-(FLO8) and PSK74852 genes were associated with higher minimum inhibitory concentration values for amphotericin B. This work may help identify mechanisms conferring azole and amphotericin B resistance in C. auris. Overall, C. auris cases from different geographic locations in Colombia exhibited high genetic relatedness, suggesting continued transmission between cities since 2016. These findings also suggest a lack of or minimal introductions of different clades of C. auris into Colombia. IMPORTANCECandida auris is an emerging fungus that presents a serious global health threat and has caused multiple outbreaks in Colombia. This work discusses the likelihood of introductions and local transmission of C. auris and provides an updated description of the molecular mechanisms associated with antifungal resistance in Colombia. Efforts like this tracking genomic variation provide information about the evolving C. auris burden that could help guide public health strategies to control C. auris spread.

genomics↗

bioRxiv2023

Single cell analysis uncovers striking cellular heterogeneity of lung infiltrating Tregs during eosinophilic vs. neutrophilic allergic airway inflammation

Allergic airway inflammation is a chronic inflammatory condition resulting from uncontrolled immune responses to environmental antigens. While it is well-established that allergic immune responses exhibit a high degree of diversity, driven by primary effector cell types like eosinophils, neutrophils, or CD4 T cells with distinct effector signatures, the exact mechanisms responsible for such pathogenesis remain largely elusive. Foxp3+ regulatory T cells (Treg) is an essential immune regulator during chronic inflammation including allergic airway inflammation. Emerging evidence suggests that Tregs infiltrating inflamed tissues exhibit distinct phenotypes dependent on the specific tissue sites and can display significant heterogeneity and tissue residency. Whether diverse allergic inflammatory responses in the lung influences infiltrating Treg heterogeneity or Treg lung residency has not previously been explored. We employed an unbiased single-cell RNAseq approach to investigate lung-infiltrating Tregs in models of eosinophilic and neutrophilic airway inflammation models, in which Tregs are critical regulators of inflammation. We found that lung-infiltrating Tregs are highly heterogeneous and that Tregs displaying lung resident phenotypes are significantly different depending on the types of inflammation. Tregs expression of ST2, a receptor for alarmin cytokine IL-33, was predominantly induced by eosinophilic inflammation and by tissue residency. However, Treg-specific ST2 deficiency did not affect the development of eosinophilic allergic inflammation nor the generation of lung resident Tregs. These results uncover a striking heterogeneity among Tregs infiltrating the lungs during allergic airway inflammation. The results also indicate that varying types of inflammation may give rise to phenotypically distinct lung resident Tregs, underscoring a novel mechanism by which inflammatory cues may shape the composition of infiltrating Tregs, allowing them to regulate inflammatory responses through tissue-adapted mechanisms.

immunology↗

bioRxiv2023

Intronic miR342 is a master regulator of cellular glycolysis in Foxp3+ regulatory CD4 T cells

Foxp3+ regulatory T (Treg) cells are a subset of CD4 T cells that play a potent and indispensable role in regulating immunity and tolerance. The precise mechanisms by which Treg cells mediate such functions have extensively been explored, and there are many cellular and molecular factors that are instrumental for adequate Treg cell functions. miRNAs, small non-coding RNA molecules, are one of the factors capable of controlling Treg cell functions. In this study, we report that miR-342 is essential for Treg cells to mitigate autoimmune inflammation in the central nervous system. Utilizing novel mouse models with Treg cell-specific miR-342 deficiency or overexpression, we demonstrate that miR-342 expression in Treg cells, while dispensable for immune homeostasis at steady-state conditions, is necessary for Treg cells to control inflammatory responses. Mechanistically, we found that Treg cells deficient in miR-342 display dysregulated metabolic profiles, elevated glycolysis and decreased oxidative phosphorylation, a metabolic phenotype associated with functionally defective Treg cells. Interestingly, miR-342-dependent metabolic dysregulation was observed in Treg but not in Th1 type cells. In support, miR-342-mediated Rictor targeting was found in Treg but not in Th1 type cells. Collectively, our findings uncover that miR-342 may serve a master regulator specific for metabolism and functions in Treg cells.

immunology↗

bioRxiv2023

Lymphocyte activation gene 3 (Lag3) supports Foxp3+ Treg cell function by restraining c-Myc-dependent aerobic glycolysis

Lymphocyte activation gene 3 (Lag3) has emerged as the next-generation immune checkpoint molecule due to its ability to inhibit effector T cell activity. Foxp3+ regulatory T (Treg) cells, a master regulator of immunity and tolerance, also highly express Lag3. While Lag3 is thought to be necessary for Treg cell-mediated regulation of immunity, the precise roles and underlying mechanisms remain largely elusive. In this study, we report that Lag3 is indispensable for Treg cells to control autoimmune inflammation. Utilizing a newly generated Treg cell specific Lag3 mutant mouse model, we found that these animals are highly susceptible to autoimmune diseases, suggesting defective Treg cell function. Genome wide transcriptome analysis further uncovered that Lag3 mutant Treg cells upregulated genes involved in metabolic processes. Mechanistically, we found that Lag3 limits Treg cell expression of Myc, a key regulator of aerobic glycolysis. We further found that Lag3-dependent Myc expression determines Treg cells metabolic programming as well as the in vivo function to suppress autoimmune inflammation. Taken together, our results uncovered a novel function of Lag3 in supporting Treg cell suppressive function by regulating Myc-dependent metabolic programming.

immunology↗

bioRxiv2022

IFN-induced protein with tetratricopeptide repeats 2 (Ifit2) limits autoimmune inflammation by regulating myeloid cell activation and metabolic activity

Besides anti-viral functions, Type I IFN expresses potent anti-inflammatory properties and is being widely used to treat certain autoimmune conditions, such as multiple sclerosis (MS). In murine model of MS, experimental autoimmune encephalomyelitis (EAE), administration of IFN{beta} effectively attenuates the disease development. However, the precise mechanisms underlying the treatment remain elusive. In this study, we report that IFN-induced protein with tetratricopeptide repeats 2 (Ifit2), a type I and type III IFN-stimulated gene, plays a previously unrecognized immune regulatory role during autoimmune neuroinflammation. Mice deficient in Ifit2 display greater susceptibility to EAE and escalated immune cell infiltration in the central nervous system. Ifit2 deficiency is also associated with microglial activation and increased myeloid cell infiltration. Unexpectedly, myelin debris clearance and the subsequent remyelination is impaired in Ifit2-/- CNS tissues. Clearing myelin debris is an important property of reparative M2 type myeloid cells to promote remyelination. Indeed, we observed that bone marrow derived macrophages, CNS infiltrating myeloid cells, and microglia from Ifit2-/- mice express cytokine and metabolic genes associated with proinflammatory M1 type subsets. Taken together, our findings uncover a novel regulatory function of Ifit2 in autoimmune inflammation in part by modulating myeloid cell function and metabolic activity.

immunology↗

bioRxiv2022

Recipient LAG3 deficiency results in antibody-mediated rejection of mouse renal allografts

Lymphocyte activation gene-3 (LAG3) is a coinhibitory receptor expressed by a range of immune cells. While immunomodulatory potential of LAG3 is being actively explored in cancer and autoimmunity fields, there is no information on how this pathway affects alloreactive immune responses following organ transplantation. The goal of this study was to investigate the functions of recipient LAG3 in a mouse model of renal allograft rejection. We found that mice deficient in LAG3 expression have elevated heterologous immunity against a panel of alloantigens prior to transplantation. Recipient LAG3 deficiency results in rapid rejection of MHC-mismatched renal allografts that are spontaneously accepted by WT recipients, with graft histology characteristic of antibody mediated rejection (ABMR). Depletion of recipient B cells but not CD8+ T cells significantly extended kidney allograft survival in LAG3-/- recipients further supporting ABMR as the main mechanism of graft loss. Treatment of WT recipients with an antagonistic LAG3 antibody enhanced anti-donor immune responses and induced kidney damage associated with chronic rejection. The experiments using conditional LAG3 knockout recipients demonstrated that LAG3 expression on either T or B cells is sufficient to regulate anti-donor humoral immunity. These results are the first to identify LAG3 as a regulator of both T and B cell responses to kidney allografts and a potential therapeutic target for ABMR prevention and treatment.

immunology↗

bioRxiv2022

Cell type specific IL-27p28 (IL-30) deletion uncovers an unexpected pro-inflammatory property of IL-30 in autoimmune inflammation

IL-27 is an IL-12 family cytokine with immune regulatory properties, capable of modulating inflammatory responses, including autoimmunity. While extensive studies investigated the major target cells of IL-27 mediating its functions, the source of IL-27 especially during tissue specific autoimmune inflammation has not formally been examined. IL-27p28 subunit, also known as IL-30, was initially discovered as an IL-27-specific subunit, and it has thus been deemed as a surrogate marker to denote IL-27 expression. However, IL-30 can be secreted independently of Ebi3, a subunit that forms bioactive IL-27 with IL-30. Moreover, IL-30 itself may act as a negative regulator antagonizing IL-27. In this study, we exploited various cell type specific IL-30-deficient mouse models and examined the source of IL-30 in T cell mediated autoimmune neuroinflammation. We found that IL-30 expressed by infiltrating and CNS resident APC subsets, infiltrating myeloid cells, microglia, and astrocytes, is key limiting the inflammation. However, dendritic cell-derived IL-30 was dispensable for the disease development. Unexpectedly, in cell type specific IL-30 deficient mice that develop severe EAE, IL-30 expression in the remaining wild-type APC subsets is disproportionately increased, suggesting that increased endogenous IL-30 production may be involved in the severe pathogenesis. In support, systemic recombinant IL-30 administration induced severe EAE. Our results demonstrate that dysregulated endogenous IL-30 expression may interfere with immune regulatory functions of IL-27, promoting encephalitogenic inflammation in vivo.

immunology↗

bioRxiv2021

Ureter single-cell and spatial mapping reveal cell types, architecture, and signaling networks

Tissue engineering offers a promising treatment strategy for ureteral strictures, but its success requires an in-depth understanding of the architecture, cellular heterogeneity, and signaling pathways underlying tissue regeneration. Here we define and spatially map cell populations within the human ureter using single-cell RNA sequencing, spatial gene expression, and immunofluorescence approaches. We focused on the stromal and urothelial cell populations to enumerate distinct cell types composing the human ureter and inferred potential cell-cell communication networks underpinning the bi-directional crosstalk between these compartments. Furthermore, we analyzed and experimentally validated the importance of Sonic Hedgehog (SHH) signaling pathway in adult stem cell maintenance. The SHH-expressing basal cells supported organoid generation in vitro and accurately predicted the differentiation trajectory from basal stem cells to terminally differentiated umbrella cells. Our results highlight essential processes involved in adult ureter tissue homeostasis and provide a blueprint for guiding ureter tissue engineering.

developmental biology↗