Diverse Subpopulations Research Articles

Single-cell and bulk transcriptome analysis reveals tumor cell heterogeneity and underlying molecular program in uveal melanoma.

Uveal melanoma (UM) is a rare and deadly eye cancer with high metastatic potential. Despite the predominance of malignant cells within the tumor microenvironment, the heterogeneity and underlying molecular features remain to be fully characterized. We analyzed single-cell transcriptomic profiling of 37,660 malignant cells from 17 UM tumors. A consensusnon-negative factorization algorithm was used to decipher transcriptional programs underlying tumor cell-intrinsic heterogeneity. Tumor-infiltrated immune cells were computationally estimated from bulk transcriptomes and bioinformatics methods. A gene signature was derived for subtyping and prognostic stratification and validated in multicenter cohorts. ScRNA-seq analysis revealed the existence of diverse subpopulations and transcriptional variability among malignant cells within and between tumors. Furthermore, we observed that the heterogeneity of malignant cell states and compositions correlated with genomic, immunological, and clinical characteristics. By identifying gene expression programs associated with malignant cell heterogeneity at the single cell level, UM samples were classified into two distinct intra-tumoral subtypes (ITMHlo and ITMHhi) with different prognoses and immune microenvironments. Finally, a machine learning-derived 9-gene signature was developed to translate single-cell information into bulk tissue transcriptomes for patient stratification and was validated in multicenter cohorts. Our study provides insight into understanding the intra-tumoral heterogeneity of UM and its potential impact on patient stratification.

Imaging mass cytometry-based characterisation of fibroblast subsets and their cellular niches in systemic sclerosis

ObjectivesTranscriptomic data demonstrated that fibroblasts are heterogeneous with functionally diverse subpopulations. Although fibroblasts are key effector cells of fibrotic diseases such as systemic sclerosis (SSc), they have not yet been...

IQGAP3 signalling mediates intratumoral functional heterogeneity to enhance malignant growth

BackgroundThe elevation of IQGAP3 expression in diverse cancers indicates a key role for IQGAP3 in carcinogenesis. Although IQGAP3 was established as a proliferating stomach stem cell factor and a regulator...

Study of the Association Between Socioeconomic Determinants and Pregnancy Follow-Up Indicators of Mothers of Low-Birth-Weight Infants: Insights for Achieving Sustainable Development Goals

Aims: This study investigates the association between socioeconomic determinants and pregnancy follow-up among 200 mothers of low-birth-weight newborns. By identifying factors influencing maternal care and birth outcomes, the study contributes to achieving Sustainable Development Goals (SDG) 3, 8, and 10, focusing on improving maternal and child health, reducing socioeconomic disparities, and ensuring equitable healthcare access. Methods: A prospective descriptive study was conducted over 12 months (June 2020–July 2021) at the neonatology and nutrition reference center of Rabat Children's Hospital. The study recruited 206 mother-child pairs, focusing on those with low-birth-weight infants. Results: Among the 200 mothers, 92% followed their pregnancies. Distribution of prenatal consultations was as follows: 0.54% had one visit, 5.98% two visits, 33.7% three, 41.85% four, and 17.93% more than four. Analysis revealed significant associations between pregnancy follow-up and socioeconomic factors. Maternal age (p < 0.001), education level (p < 0.001), and place of residence significantly influenced pregnancy monitoring, with urban mothers more likely to receive follow-up care. Single mothers had a 100% non-tracking rate, while married mothers predominantly monitored their pregnancies. Conclusions: This study demonstrates the strong influence of sociodemographic factors on antenatal care use, aligning with findings from other contexts. It contributes new insights into the specific characteristics of our study population and has practical implications for shaping maternal and child health policies, addressing the unique needs of diverse sub-populations. Achieving SDG 3 (Good Health and Well-being), SDG 8 (Decent Work and Economic Growth), and SDG 10 (Reduced Inequalities) requires targeted interventions that improve equitable access to quality maternal care.

Hypoxia sensing in resident cardiac macrophages regulates monocyte fate specification following ischemic heart injury.

Myocardial infarction initiates cardiac remodeling and is central to heart failure pathogenesis. Following myocardial ischemia-reperfusion injury, monocytes enter the heart and differentiate into diverse subpopulations of macrophages. Here we show that deletion of Hif1α, a hypoxia response transcription factor, in resident cardiac macrophages led to increased remodeling and overrepresentation of macrophages expressing arginase 1 (Arg1). Arg1+ macrophages displayed an inflammatory gene signature and may represent an intermediate state of monocyte differentiation. Lineage tracing of Arg1+ macrophages revealed a monocyte differentiation trajectory consisting of multiple transcriptionally distinct states. We further showed that deletion of Hif1α in resident cardiac macrophages resulted in arrested progression through this trajectory and accumulation of an inflammatory intermediate state marked by persistent Arg1 expression. Depletion of the Arg1+ trajectory accelerated cardiac remodeling following ischemic injury. Our findings unveil distinct trajectories of monocyte differentiation and identify hypoxia sensing as an important determinant of monocyte differentiation following myocardial infarction.

Black Community Health Advocates in Ontario: A Look at Health Policy Engagement From the Ground Up.

Disproportionately negative pandemic outcomes, lack of race-based data collection and poor engagement of Black communities in policy decision making have been widely documented for Black Canadians. We examine this to understand how formal public engagement processes might be more inclusive of Black peoples to inform more responsive policies. The study employed an asset-based lens to examine how Black communities have engaged in health policy and advocacy in Ontario. In-depth interviews were conducted with eight participants who self-identify as Black, recruited using purposive and intensity sampling to (1) identify information-rich cases, including people who have been at the forefront of high-impact work in this space and (2) participants whose mission and mandates represented diverse approaches and sub-populations. Our findings suggest that while Black community advocates face systemic and contextual barriers, they also embody deep and multifaceted knowledge, training and experience, which inform the rich ways that they approach advocacy. Despite its Ontario focus, this study adds breadth and depth to the existing literature on health policy and historically marginalized populations, offering broader lessons for policy makers across jurisdictions. Our findings encourage policy makers to better recognize, make space for and cultivate fertile advocacy foundations, cultural knowledge and community-driven systems already present in Black communities.

The quiet revolution: Send-down movement and female empowerment in China

What promotes female empowerment and gender equality? We investigate how internal population mobility and social interaction foster the advancement of female empowerment and gender equality across diverse subpopulations. Using the urban-to-rural youth resettlement program in China during the 1970s — the Send-down Movement — as our empirical context, we find that rural females with greater exposure to urban youths have achieved higher levels of education, increased labor force participation, greater financial independence, enhanced autonomy in marital and fertility decisions, increased political engagement, heightened self-confidence, reduced risk aversion, and a stronger belief in gender-equal ideologies and social values. Our findings underscore the role of population mobility in disseminating gender-equal ideologies and practices, both through human capital formation and social interactions, leading to lasting impacts on female empowerment in traditional societies.

Impact of complete versus culprit-only revascularization on major adverse cardiovascular event in diverse subpopulations.

Background: Myocardial infarction management relies on pharmaceuticals and interventions like percutaneous coronary intervention (PCI). While complete PCI has shown noninferiority to culprit-only PCI, its impact on major adverse cardiovascular events (MACE) outcomes in multiple subpopulations has been unknown.Methods: A systematic literature search (from January 2000 to May 2024) identified four relevant randomized controlled trials involving ST-segment elevation myocardial infarction patients. Data analysis employed a random-effects model with inverse variance weighting.Results: MACE risk was significantly lower in males than females undergoing complete PCI compared with culprit-only PCI (hazard ratio: 0.52; 95% CI: 0.39-0.68; p<0.01; I2=53%). Furthermore, complete PCI significantly lowered the risk of MACE outcomes in patients without diabetes and in patients under the 65-year age limit in comparison to culprit-only PCI.Conclusion: Complete PCI reduces MACE risk in male, nondiabetic ST-segment elevation myocardial infarction patients under 65 with multivessel coronary artery disease, necessitating further investigation into outcome differences among different subpopulations.

Morpho-physiological Diversity of Cholecystokinin-expressing Interneurons in the Dentate Gyrus.

The hippocampus plays a crucial role in learning, memory, and emotion, with the dentate gyrus (DG) serving as the primary gateway. The DG receives multimodal sensory inputs from outside the hippocampus and relays this integrated information to downstream regions for further processing. Within the DG, inhibitory GABAergic interneurons (INs) regulate information processing, thereby influencing the overall hippocampal function. Cholecystokinin (CCK)-expressing INs in the DG are particularly implicated in emotional behavior due to their expression of cannabinoid and serotonin receptors. However, studying the morpho-electrophysiological features and functions of these INs has been challenging due to the off-target labeling of granule cells (GCs), the primary excitatory neurons in the DG, when using the CCK recombinase driver line. To address this issue, we employed an intersectional strategy to selectively label CCK INs, allowing us to investigate their electrophysiological, morphological, and synaptic features, which were further confirmed by post hoc pro-CCK immunostaining. Our analysis identified nine distinct subtypes of CCK INs, each with unique projection patterns targeting specific domains along the axo-somato-dendritic axis of GCs. CCK INs also exhibited diverse passive intrinsic properties and firing patterns. In addition, we found that CCK INs generate action potentials before GCs in response to cortical input, suggesting that they play a role in modulating GC input-output transformation. In summary, our findings indicate that DG CCK INs are diverse subpopulations with distinct roles in network functions.

Evaluating in vivo approaches for studying the roles of thymic DCs in T cell development in mice.

T cells express an enormous repertoire of T cell receptors, enabling them to recognize any potential antigen. This large repertoire undergoes stringent selections in the thymus, where receptors that react to self- or non-danger-associated- antigens are purged. We know that thymic tolerance depends on signals and antigens presented by the thymic antigen presenting cells, but we still do not understand precisely how many of these cells actually contribute to tolerance. This is especially true for thymic dendritic cells (DC), which are composed of diverse subpopulations that are derived from different progenitors. Although the importance of thymic DCs has long been known, the functions of specific DC subsets have been difficult to untangle. There remains insufficient systematic characterization of the ontogeny and phenotype of thymic APCs in general. As a result, validated experimental models for studying thymic DCs are limited. Recent technological advancement, such as multi-omics analyses, has enabled new insights into thymic DC biology. These recent findings indicate a need to re-evaluate the current tools used to study the function of these cells within the thymus. This review will discuss how thymic DC subpopulations can be defined, the models that have been used to assess functions in the thymus, and models developed for other settings that can be potentially used for studying thymic DCs.

Comprehensive analysis of root canal morphology in maxillary premolars among the Pakistani subpopulation: a CBCT-based study

BackgroundUnderstanding the root canal morphology is essential for the success of root canal treatment. Therefore, this study aimed to evaluate and analyze the root canal configuration of maxillary premolars using Cone Beam Computed Tomography in the Pakistani subpopulation.MethodThis cross-sectional study utilized CBCT scans from two distinct centres: Aga Khan University in Karachi and Jinnah MRI and Body Scans in Lahore. The CBCT images were visualized using GALAXIS version 1.9 (SICAT GmbH and Co. KG, Bonn, Germany), integrated within the Sirona Dental System (D-64625 Bensheim, Germany). The scanning parameters were standardized at 85 kV, 7 mA, with a 15-s exposure time and a voxel size of 0.16 mm. A total of 707 CBCT scans were collected, encompassing 2180 maxillary premolars. Root canal configurations were classified based on (Ahmed et al. Int Endod J. 2017;50(8):761–70). Statistical analyses were performed using SPSS version 26, employing the Chi-square test with a significance level set at p < 0.05.ResultsThe distribution of root canal morphologies varied significantly with age and gender. Among maxillary premolars, 50% exhibited the typical configuration of 2MPMB1 L1 (two roots, single canal in each buccal and lingual root), while 26% of maxillary right second premolars displayed 1MPM1 (one root, one canal). Overall, 1MPM1 accounted for 27.4% of the total cases in the second premolars. There was no statistically significant relationship between age and root canal distribution in either first premolars (p = 0.338) or second premolars (p = 0.833). Regarding gender, a significant difference was observed in the distribution of right maxillary 1st premolars (p = 0.022*), with a higher prevalence among females.ConclusionThis study offers significant insights into the anatomical variations of root canals in maxillary premolars across diverse regional subpopulations in Pakistan. While specific root canal configurations were prevalent, the findings indicate no statistically significant correlation between age and root canal morphology in maxillary premolars. However, a notable gender disparity was observed in the distribution of the right maxillary first premolars.

IS1-mediated chromosomal amplification of the arn operon leads to polymyxin B resistance in Escherichia coli B strains.

Polymyxins [colistin and polymyxin B (PMB)] comprise an important class of natural product lipopeptide antibiotics used to treat multidrug-resistant Gram-negative bacterial infections. These positively charged lipopeptides interact with lipopolysaccharide (LPS) located in the outer membrane and disrupt the permeability barrier, leading to increased uptake and bacterial cell death. Many bacteria counter polymyxins by upregulating genes involved in the biosynthesis and transfer of amine-containing moieties to increase positively charged residues on LPS. Although 4-deoxy-l-aminoarabinose (Ara4N) and phosphoethanolamine (PEtN) are highly conserved LPS modifications in Escherichia coli, different lineages exhibit variable PMB susceptibilities and frequencies of resistance for reasons that are poorly understood. Herein, we describe a mechanism prevalent in E. coli B strains that depends on specific insertion sequence 1 (IS1) elements that flank genes involved in the biosynthesis and transfer of Ara4N to LPS. Spontaneous and transient chromosomal amplifications mediated by IS1 raise the frequency of PMB resistance by 10- to 100-fold in comparison to strains where a single IS1 element located 90 kb away from the end of the arn operon has been deleted. Amplification involving IS1 becomes the dominant resistance mechanism in the absence of PEtN modification. Isolates with amplified arn operons gradually lose their PMB-resistant phenotype with passaging, consistent with classical PMB heteroresistance behavior. Analysis of the whole genome transcriptome profile showed altered expression of genes residing both within and outside of the duplicated chromosomal segment, suggesting complex phenotypes including PMB resistance can result from tandem amplification events.IMPORTANCEPhenotypic variation in susceptibility and the emergence of resistant subpopulations are major challenges to the clinical use of polymyxins. While a large database of genes and alleles that can confer polymyxin resistance has been compiled, this report demonstrates that the chromosomal insertion sequence (IS) content and distribution warrant consideration as well. Amplification of large chromosomal segments containing the arn operon by IS1 increases the Ara4N content of the lipopolysaccharide layer in Escherichia coli B lineages using a mechanism that is orthogonal to transcriptional upregulation through two-component regulatory systems. Altogether, our work highlights the importance of IS elements in modulating gene expression and generating diverse subpopulations that can contribute to phenotypic polymyxin B heteroresistance.

Elucidating the multifaceted role of MGAT1 in hepatocellular carcinoma: integrative single-cell and spatial transcriptomics reveal novel therapeutic insights.

Glycosyltransferase-associated genes play a crucial role in hepatocellular carcinoma (HCC) pathogenesis. This study investigates their impact on the tumor microenvironment and molecular mechanisms, offering insights into innovative immunotherapeutic strategies for HCC. We utilized cutting-edge single-cell and spatial transcriptomics to examine HCC heterogeneity. Four single-cell scoring techniques were employed to evaluate glycosyltransferase genes. Spatial transcriptomic findings were validated, and bulk RNA-seq analysis was conducted to identify prognostic glycosyltransferase-related genes and potential immunotherapeutic targets. MGAT1's role was further explored through various functional assays. Our analysis revealed diverse cell subpopulations in HCC with distinct glycosyltransferase gene activities, particularly in macrophages. Key glycosyltransferase genes specific to macrophages were identified. Temporal analysis illustrated macrophage evolution during tumor progression, while spatial transcriptomics highlighted reduced expression of these genes in core tumor macrophages. Integrating scRNA-seq, bulk RNA-seq, and spatial transcriptomics, MGAT1 emerged as a promising therapeutic target, showing significant potential in HCC immunotherapy. This comprehensive study delves into glycosyltransferase-associated genes in HCC, elucidating their critical roles in cellular dynamics and immune cell interactions. Our findings open new avenues for immunotherapeutic interventions and personalized HCC management, pushing the boundaries of HCC immunotherapy.

CD38+ Alveolar macrophages mediate early control of M. tuberculosis proliferation in the lung.

Tuberculosis, caused by M.tuberculosis (Mtb), remains an enduring global health challenge, especially given the limited efficacy of current therapeutic interventions. Much of existing research has focused on immune failure as a driver of tuberculosis. However, the crucial role of host macrophage biology in controlling the disease remains underappreciated. While we have gained deeper insights into how alveolar macrophages (AMs) interact with Mtb, the precise AM subsets that mediate protection and potentially prevent tuberculosis progression have yet to be identified. In this study, we employed multi-modal scRNA-seq analyses to evaluate the functional roles of diverse macrophage subpopulations across different infection timepoints, allowing us to delineate the dynamic landscape of controller and permissive AM populations during the course of infection. Our analyses at specific time-intervals post-Mtb challenge revealed macrophage populations transitioning between distinct anti- and pro-inflammatory states. Notably, early in Mtb infection, CD38- AMs showed a muted response. As infection progressed, we observed a phenotypic shift in AMs, with CD38+ monocyte-derived AMs (moAMs) and a subset of tissue-resident AMs (TR-AMs) emerging as significant controllers of bacterial growth. Furthermore, scATAC-seq analysis of naïve lungs demonstrated that CD38+ TR-AMs possessed a distinct chromatin signature prior to infection, indicative of epigenetic priming and predisposition to a pro-inflammatory response. BCG intranasal immunization increased the numbers of CD38+ macrophages, substantially enhancing their capability to restrict Mtb growth. Collectively, our findings emphasize the pivotal, dynamic roles of different macrophage subsets in TB infection and reveal rational pathways for the development of improved vaccines and immunotherapeutic strategies.

Non-genetic heterogeneity and immune subtyping in breast cancer: Implications for immunotherapy and targeted therapeutics

Breast cancer (BC) is a complex and multifactorial disease, driven by genetic alterations that promote tumor growth and progression. However, recent research has highlighted the importance of non-genetic factors in shaping cancer evolution and influencing therapeutic outcomes. Non-genetic heterogeneity refers to diverse subpopulations of cancer cells within breast tumors, exhibiting distinct phenotypic and functional properties. These subpopulations can arise through various mechanisms, including clonal evolution, genetic changes, epigenetic changes, and reversible phenotypic transitions. Although genetic and epigenetic changes are important points of the pathology of breast cancer yet, the immune system also plays a crucial role in its progression. In clinical management, histologic and molecular classification of BC are used. Immunological subtyping of BC has gained attention in recent years as compared to traditional techniques. Intratumoral heterogeneity revealed by immunological microenvironment (IME) has opened novel opportunities for immunotherapy research. This systematic review is focused on non-genetic variability to identify and interlink immunological subgroups in breast cancer. This review provides a deep understanding of adaptive methods adopted by tumor cells to withstand changes in the tumor microenvironment and selective pressure imposed by medications. These adaptive methods include alterations in drug targets, immune system evasion, activation of survival pathways, and alterations in metabolism. Understanding non-genetic heterogeneity is essential for the development of targeted therapies.

Fairness gaps in Machine learning models for hospitalization and emergency department visit risk prediction in home healthcare patients with heart failure

ObjectivesThis study aims to evaluate the fairness performance metrics of Machine Learning (ML) models to predict hospitalization and emergency department (ED) visits in heart failure patients receiving home healthcare. We analyze biases, assess performance disparities, and propose solutions to improve model performance in diverse subpopulations. MethodsThe study used a dataset of 12,189 episodes of home healthcare collected between 2015 and 2017, including structured (e.g., standard assessment tool) and unstructured data (i.e., clinical notes). ML risk prediction models, including Light Gradient-boosting model (LightGBM) and AutoGluon, were developed using demographic information, vital signs, comorbidities, service utilization data, and the area deprivation index (ADI) associated with the patient’s home address. Fairness metrics, such as Equal Opportunity, Predictive Equality, Predictive Parity, and Statistical Parity, were calculated to evaluate model performance across subpopulations. ResultsOur study revealed significant disparities in model performance across diverse demographic subgroups. For example, the Hispanic, Male, High-ADI subgroup excelled in terms of Equal Opportunity with a metric value of 0.825, which was 28% higher than the lowest-performing Other, Female, Low-ADI subgroup, which scored 0.644. In Predictive Parity, the gap between the highest and lowest-performing groups was 29%, and in Statistical Parity, the gap reached 69%. In Predictive Equality, the difference was 45%. Discussion and ConclusionThe findings highlight substantial differences in fairness metrics across diverse patient subpopulations in ML risk prediction models for heart failure patients receiving home healthcare services. Ongoing monitoring and improvement of fairness metrics are essential to mitigate biases.

Biomimetic Approach of Brain Vasculature Rapidly Characterizes Inter- and Intra-Patient Migratory Diversity of Glioblastoma.

Glioblastomas exhibit remarkable heterogeneity at various levels, including motility modes and mechanoproperties that contribute to tumor resistance and recurrence. In a recent study using gridded micropatterns mimicking the brain vasculature, glioblastoma cell motility modes, mechanical properties, formin content, and substrate chemistry are linked. Now is presented, SP2G (SPheroid SPreading on Grids), an analytic platform designed to identify the migratory modes of patient-derived glioblastoma cells and rapidly pinpoint the most invasive sub-populations. Tumorspheres are imaged as they spread on gridded micropatterns and analyzed by this semi-automated, open-source, Fiji macro suite that characterizes migration modes accurately. SP2G can reveal intra-patient motility heterogeneity with molecular correlations to specific integrins and EMT markers. This system presents a versatile and potentially pan-cancer workflow to detect diverse invasive tumor sub-populations in patient-derived specimens and offers a valuable tool for therapeutic evaluations at the individual patient level.

Impact of doxorubicin-loaded ferritin nanocages (FerOX) vs. free doxorubicin on T lymphocytes: a translational clinical study on breast cancer patients undergoing neoadjuvant chemotherapy

Despite the advent of numerous targeted therapies in clinical practice, anthracyclines, including doxorubicin (DOX), continue to play a pivotal role in breast cancer (BC) treatment. DOX directly disrupts DNA replication, demonstrating remarkable efficacy against BC cells. However, its non-specificity toward cancer cells leads to significant side effects, limiting its clinical utility. Interestingly, DOX can also enhance the antitumor immune response by promoting immunogenic cell death in BC cells, thereby facilitating the presentation of tumor antigens to the adaptive immune system. However, the generation of an adaptive immune response involves highly proliferative processes, which may be adversely affected by DOX-induced cytotoxicity. Therefore, understanding the impact of DOX on dividing T cells becomes crucial, to deepen our understanding and potentially devise strategies to shield anti-tumor immunity from DOX-induced toxicity. Our investigation focused on studying DOX uptake and its effects on human lymphocytes. We collected lymphocytes from healthy donors and BC patients undergoing neoadjuvant chemotherapy (NAC). Notably, patient-derived peripheral blood mononuclear cells (PBMC) promptly internalized DOX when incubated in vitro or isolated immediately after NAC. These DOX-treated PBMCs exhibited significant proliferative impairment compared to untreated cells or those isolated before treatment initiation. Intriguingly, among diverse lymphocyte sub-populations, CD8 + T cells exhibited the highest uptake of DOX. To address this concern, we explored a novel DOX formulation encapsulated in ferritin nanocages (FerOX). FerOX specifically targets tumors and effectively eradicates BC both in vitro and in vivo. Remarkably, only T cells treated with FerOX exhibited reduced DOX internalization, potentially minimizing cytotoxic effects on adaptive immunity.Our findings underscore the importance of optimizing DOX delivery to enhance its antitumor efficacy while minimizing adverse effects, highlighting the pivotal role played by FerOX in mitigating DOX-induced toxicity towards T-cells, thereby positioning it as a promising DOX formulation. This study contributes valuable insights to modern cancer therapy and immunomodulation.

Temporal Trends in Cardiovascular Disease Prevalence Among Asian American Subgroups.

Asian and multiracial individuals represent the 2fastest growing racial and ethnic groups in the United States, yet most prior studies report Asian American and Native Hawaiian or Other Pacific Islander as a single racial group, with limited data on cardiovascular disease (CVD) prevalence among subgroups. We sought to evaluate temporal trends in CVD burden among disaggregated Asian subgroups. Patients with CVD based on International Classification of Diseases, Ninth Revision and Tenth Revision (ICD-9 and ICD-10) coding who received care from a mixed-payer health care organization in California between 2008 and 2018 were classified into self-identified racial and ethnic subgroups (non-Hispanic White [NHW], Asian Indian, Chinese, Filipino, Japanese, Korean, Native Hawaiian or Other Pacific Islander, and multiracial groups). Adjusted trends in CVD prevalence over time by subgroup were compared using logistic regression. Among 3 494 071 patient-years, prevalence of CVD increased faster among all subgroups except Japanese and Native Hawaiian or Other Pacific Islander patients (P<0.01 for each, reference: NHW). Filipino patients had the highest overall CVD prevalence, which increased from 34.3% to 45.1% over 11 years (increase from 17.3%-21.9%, P<0.0001, reference: NHW). Asian Indian patients had the fastest increase in CVD prevalence over time (16.9%-23.7%, P<0.0001, reference: NHW). Among subcategories of disease, hypertension increased faster among Asian Indian, Chinese, Filipino, Korean, and multiracial groups (P<0.01 for all, reference: NHW), and coronary artery disease increased faster among Asian Indian, Chinese, Filipino, and Japanese groups (P<0.05 for each, reference: NHW). The increasing prevalence of CVD among disaggregated Asian, Native Hawaiian or Other Pacific Islander, and multiracial subgroups over time highlights the importance of tailored approaches to addressing CVD in these diverse subpopulations.

Single-cell analysis of mesenchymal cells in permeable neural vasculature reveals novel diverse subpopulations of fibroblasts

BackgroundIn the choroid plexus and pituitary gland, vasculature is known to have a permeable, fenestrated phenotype which allows for the free passage of molecules in contrast to the blood brain barrier observed in the rest of the CNS. The endothelium of these compartments, along with secretory, neural-lineage cells (choroid epithelium and pituitary endocrine cells) have been studied in detail, but less attention has been given to the perivascular mesenchymal cells of these compartments.MethodsThe Hic1CreERT2 Rosa26LSL−TdTomato mouse model was used in conjunction with a PdgfraH2B−EGFP mouse model to examine mesenchymal cells, which can be subdivided into Pdgfra+ fibroblasts and Pdgfra− pericytes within the choroid plexus (CP) and pituitary gland (PG), by histological, immunofluorescence staining and single-cell RNA-sequencing analyses.ResultsWe found that both CP and PG possess substantial populations of distinct Hic1+ mesenchymal cells, including an abundance of Pdgfra+ fibroblasts. Within the pituitary, we identified distinct subpopulations of Hic1+ fibroblasts in the glandular anterior pituitary and the neurosecretory posterior pituitary. We also identified multiple distinct markers of CP, PG, and the meningeal mesenchymal compartment, including alkaline phosphatase, indole-n-methyltransferase and CD34.ConclusionsNovel, distinct subpopulations of mesenchymal cells can be found in permeable vascular interfaces, including the CP, PG, and meninges, and make distinct contributions to both organs through the production of structural proteins, enzymes, transporters, and trophic molecules.