Insights on Literacy From Stroke Survivors With Aphasia: A Mixed-Methods Inquiry.

PURPOSE: Individuals with aphasia commonly experience reading and writing difficulties, negatively impacting everyday communication and life participation. Using mixed methods, this study aimed to understand literacy experiences described by individuals with aphasia and explore how their perspectives are related to test performance and other demographic factors. METHOD: Twenty-one stroke survivors with aphasia completed reading and writing testing and shared their perspectives through a close-ended survey and an open-ended interview about literacy abilities and experiences. Quantitative methods were used to compare pre- and poststroke self-ratings and explore associations between self-ratings and demographic factors. Qualitative methods were used to identify themes in the interviews. The data sets were merged to derive mixed-methods results for a more in-depth view of participants' perspectives. RESULTS: Significant decreases in perceived literacy abilities were found; however, there were no differences in literacy importance or enjoyment pre- to poststroke. Reading and writing test scores were correlated with self-rated abilities but not with importance, enjoyment, or frequency of reading and writing. The thematic analysis process identified four main themes: Feelings about literacy, Literacy challenges, Literacy supports, and Literacy goals. CONCLUSIONS: The data indicate that individuals with aphasia highly value reading and writing and are heavily invested, despite recognized challenges, in using and improving these skills. Therefore, assessments and treatments addressing literacy in aphasia are critical, and individuals with aphasia should be invited to share their literacy experiences and goals, allowing for more person-centered clinical resources to be collaboratively constructed. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25893049.

Identification and Pharmacological Targeting of Treatment-Resistant, Stem-like Breast Cancer Cells for Combination Therapy.

Tumors frequently harbor isogenic yet epigenetically distinct subpopulations of multi-potent cells with high tumor-initiating potential-often called Cancer Stem-Like Cells (CSLCs). These can display preferential resistance to standard-of-care chemotherapy. Single-cell analyses can help elucidate Master Regulator (MR) proteins responsible for governing the transcriptional state of these cells, thus revealing complementary dependencies that may be leveraged via combination therapy. Interrogation of single-cell RNA sequencing profiles from seven metastatic breast cancer patients, using perturbational profiles of clinically relevant drugs, identified drugs predicted to invert the activity of MR proteins governing the transcriptional state of chemoresistant CSLCs, which were then validated by CROP-seq assays. The top drug, the anthelmintic albendazole, depleted this subpopulation in vivo without noticeable cytotoxicity. Moreover, sequential cycles of albendazole and paclitaxel-a commonly used chemotherapeutic -displayed significant synergy in a patient-derived xenograft (PDX) from a TNBC patient, suggesting that network-based approaches can help develop mechanism-based combinatorial therapies targeting complementary subpopulations.

Students' Perception of a Virtual Dissection Laboratory in Undergraduate Anatomy and Physiology of Speech and Hearing: A Focus Group Study.

Hands-on laboratory experience that allows for manipulation of realistic and relevant materials in course curricula has been shown to improve students' learning, understanding, and critical thinking skills. The purpose of this study was to gain insight into the experiences of students who engaged in laboratory coursework using a virtual dissection (VD) table as part of an undergraduate course in anatomy and physiology of speech and hearing. Undergraduate students enrolled in an anatomy and physiology of speech and hearing course at a single university for the fall 2021 semester consented to participate. Nine students, divided into two focus groups, were encouraged to describe their experiences and perspectives about the VD table and corresponding laboratory assignments. Following verbatim transcription of the data, the authors conducted a thematic analysis. Five themes emerged from the body of data: (1) using the VD table, (2) completing the VD lab assignments, (3) preparation for laboratory sessions, (4) suggested modifications, and (5) enriched learning. Students believed using the VD table aided in a better understanding of course material than traditional methods. Moreover, they surmised that this method of learning, particularly for speech-language pathologists, may be superior to learning through models and cadavers.

Gluten induces rapid reprogramming of natural memory αß and γδ intraepithelial T cells to induce cytotoxicity in celiac disease.

Celiac disease (CD) is an autoimmune disease in which intestinal inflammation is induced by dietary gluten. The means through which gluten-specific CD4+ T cell activation culminates in intraepithelial T cell (T-IEL)-mediated intestinal damage remain unclear. Here, we performed multiplexed single-cell analysis of intestinal and gluten-induced peripheral blood T cells from patients in different CD states and healthy controls. Untreated, active, and potential CD were associated with an enrichment of activated intestinal T cell populations, including CD4+ follicular T helper (TFH) cells, regulatory T cells (Tregs), and natural CD8+ αß and γδ T-IELs. Natural CD8+ αß and γδ T-IELs expressing activating natural killer cell receptors (NKRs) exhibited a distinct TCR repertoire in CD and persisted in patients on a gluten-free diet without intestinal inflammation. Our data further show that NKR-expressing cytotoxic cells, which appear to mediate intestinal damage in CD, arise from a distinct NKR-expressing memory population of T-IELs. After gluten ingestion, both αß and γδ T cell clones from this memory population of T-IELs circulated systemically along with gluten-specific CD4+ T cells and assumed a cytotoxic and activating NKR-expressing phenotype. Collectively, these findings suggest that cytotoxic T cells in CD are rapidly mobilized in parallel with gluten-specific CD4+ T cells after gluten ingestion.

Re-convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue states.

Glioblastoma (GBM) diffusely infiltrates the brain and intermingles with non-neoplastic brain cells, including astrocytes, neurons and microglia/myeloid cells. This complex mixture of cell types forms the biological context for therapeutic response and tumor recurrence. We used single-nucleus RNA sequencing and spatial transcriptomics to determine the cellular composition and transcriptional states in primary and recurrent glioma and identified three compositional 'tissue-states' defined by cohabitation patterns between specific subpopulations of neoplastic and non-neoplastic brain cells. These tissue-states correlated with radiographic, histopathologic, and prognostic features and were enriched in distinct metabolic pathways. Fatty acid biosynthesis was enriched in the tissue-state defined by the cohabitation of astrocyte-like/mesenchymal glioma cells, reactive astrocytes, and macrophages, and was associated with recurrent GBM and shorter survival. Treating acute slices of GBM with a fatty acid synthesis inhibitor depleted the transcriptional signature of this pernicious tissue-state. These findings point to therapies that target interdependencies in the GBM microenvironment.

Considerations for Voice and Communication Training Software for Transgender and Nonbinary People.

Transgender and gender diverse people often experience voice-gender incongruence, which is inversely correlated with health and quality of life. Such incongruence could be reduced with voice and communication training, but expert-administered training is often inaccessible while self-guided training is difficult and potentially risky. Training could alternatively be provided through software (eg, smartphone apps), but such software is at an early stage. This qualitatively driven mixed-methods study thus includes surveys and interviews with 21 transfeminine, transmasculine and nonbinary people to identify general views of voice and communication training software as well as most desirable features of such software. Participants were positive about the general idea and described ways to effectively implement four critical features: feedback, accountability, automated goal setting, and training characteristics other than pitch. They also discussed optional or undesirable features. These findings may inform development of voice and communication training software, thus improving health and quality of life for gender minorities.

Critical and Creative Thinking and Photovoice: Strategies for Strengthening Participation and Inclusion.

Researchers, nonprofit organizations, and others have long used photovoice as a participatory action research method with vulnerable groups to depict, reflect on, and describe their realities, and advocate for change. Paulo Freire, whose scholarship is a foundation of photovoice, encouraged critical thinking in a popular education process to understand "the 'why' of things and facts." Creative thinking, a complementary concept that emerged in the field of education in the 1990s, involves, at its core, development, implementation, and communication of multiple original ideas. We provide a model of critical and creative thinking as an integrated process that generates knowledge as participants complete four key photovoice steps: (1) answer questions with a camera, (2) communicate in the group, (3) observe commonalities, and (4) communicate to power. We argue that each step involves teachable skills and provide practical, low-tech strategies that photovoice facilitators can use to enhance critical and creative thinking by any participant who finds it challenging to complete the four steps. Bringing a critical and creative thinking process to photovoice facilitation grounds the method in its education roots. It can enhance participation and inclusion of any vulnerable group, including people with cognitive and communication disorders due to acquired brain injury, mental illness, or substance use disorder for example. We suggest that use of the suggested strategies will result in an authentic, meaningful process that helps equalize power relationships, respects individuals as experts on their own lives, and increases the potential for data that prompt action.

Coordinated speech therapy, physiotherapy, and pharmaceutical care telehealth for people with Parkinson disease in rural communities: an exploratory, 8-week cohort study for feasibility, safety, and signal of efficacy.

INTRODUCTION: The potential for coordinated, multidisciplinary telehealth to help connect people with Parkinson disease (PD) in rural areas to PD specialists is crucial in optimizing care. Therefore, this study aimed to test the feasibility, safety, and signal of efficacy of a coordinated telehealth program, consisting of speech therapy, physiotherapy, and pharmaceutical care, for people with PD living in some rural US communities. METHODS: Fifteen individuals with PD living in rural Wyoming and Nevada, USA, participated in this single-cohort, 8-week pilot study. Participants were assessed before and after 8 weeks of coordinated, one-on-one telehealth using the following outcomes: (1) feasibility: session attendance and withdrawal rate; (2) safety: adverse events; and (3) signal of efficacy: Communication Effectiveness Survey, acoustic data (intensity, duration, work (intensity times duration)), Parkinson's Fatigue Scale, 30 second Sit-to-Stand test, Parkinson's Disease Questionnaire - 39, Movement Disorder Society Unified Parkinson's Disease Rating Scale - Part III, and medication adherence. RESULTS: Average attendance was greater than 85% for all participants. There were no serious adverse events and only nine minor events during treatment sessions (0.9% of all treatment sessions had a participant report of an adverse event); all nine cases resolved without medical attention. Although 14 of 16 outcomes had effect sizes trending in the direction of improvement, only two were statistically significant using non-parametric analyses: 30 second Sit-to-Stand (pre-test median=11.0 (interquartile range (IQR)=6.0); post-test median=12.0 (IQR=3.0) and acoustic data work (pre-test median=756.0 dB s (IQR=198.4); post-test median=876.3 dB s (IQR=455.5), p<0.05. CONCLUSION: A coordinated, multidisciplinary telehealth program was safe and feasible for people in rural communities who have PD. This telehealth program also yielded a signal of efficacy for most of the outcomes measured in the study.

Single-Cell Genomics Reveals a Novel Cell State During Smooth Muscle Cell Phenotypic Switching and Potential Therapeutic Targets for Atherosclerosis in Mouse and Human.

BACKGROUND: Smooth muscle cells (SMCs) play significant roles in atherosclerosis via phenotypic switching, a pathological process in which SMC dedifferentiation, migration, and transdifferentiation into other cell types. Yet how SMCs contribute to the pathophysiology of atherosclerosis remains elusive. METHODS: To reveal the trajectories of SMC transdifferentiation during atherosclerosis and to identify molecular targets for disease therapy, we combined SMC fate mapping and single-cell RNA sequencing of both mouse and human atherosclerotic plaques. We also performed cell biology experiments on isolated SMC-derived cells, conducted integrative human genomics, and used pharmacological studies targeting SMC-derived cells both in vivo and in vitro. RESULTS: We found that SMCs transitioned to an intermediate cell state during atherosclerosis, which was also found in human atherosclerotic plaques of carotid and coronary arteries. SMC-derived intermediate cells, termed "SEM" cells (stem cell, endothelial cell, monocyte), were multipotent and could differentiate into macrophage-like and fibrochondrocyte-like cells, as well as return toward the SMC phenotype. Retinoic acid (RA) signaling was identified as a regulator of SMC to SEM cell transition, and RA signaling was dysregulated in symptomatic human atherosclerosis. Human genomics revealed enrichment of genome-wide association study signals for coronary artery disease in RA signaling target gene loci and correlation between coronary artery disease risk alleles and repressed expression of these genes. Activation of RA signaling by all-trans RA, an anticancer drug for acute promyelocytic leukemia, blocked SMC transition to SEM cells, reduced atherosclerotic burden, and promoted fibrous cap stability. CONCLUSIONS: Integration of cell-specific fate mapping, single-cell genomics, and human genetics adds novel insights into the complexity of SMC biology and reveals regulatory pathways for therapeutic targeting of SMC transitions in atherosclerotic cardiovascular disease.

Single-Cell Transcriptional Profiling of the Intestinal Epithelium.

Emerging single-cell technologies, like single-cell RNA sequencing (scRNA-seq), enable the study of heterogeneous biological systems at cellular resolution. By profiling the set of expressed transcripts in each cell, single-cell transcriptomics has allowed for the cataloging of the cellular constituents of multiple organs and tissues, both in health and disease. In addition, these technologies have provided mechanistic insights into cellular function, cell state transitions, developmental trajectories and lineage relationships, as well as helped to dissect complex, population-level responses to environmental perturbations. scRNA-seq is particularly useful for characterizing the intestinal epithelium because it is a dynamic, rapidly self-renewing tissue comprised of more than a dozen specialized cell types. Here we discuss the fundamentals of single-cell transcriptomics of the murine small intestinal epithelium. We review the principles of proper experimental design and provide methods for the dissociation of the small intestinal epithelium into single cells followed by fluorescence-activated cell sorting (FACS) and for scRNA-seq using the 10× Genomics Chromium platform.

Describing the Composition of Individualized Education Plans for Students With Traumatic Brain Injury.

Purpose The purpose of this study was to explore and describe the features of Individualized Education Plans (IEPs) for a cohort of students with traumatic brain injury (TBI) to help elucidate current special education practices for students with TBI. Method We obtained permission from administrators of a local school district of 41,000 students in a Midwestern state to review de-identified IEP records of students verified with TBI. We examined demographic information (i.e., cause and age at time of injury), IEP services and intensity, IEP goal categories, and previous verification status. Results Descriptive results support that intervention services were more intense for students with TBI with greater lengths of time postinjury. Target behaviors within goals were more often related to math and reading than to the cognitive processes that govern these skills, such as attention, memory, and executive functioning. Finally, more than a third of our sample had been verified with a disability and were receiving special education services via an IEP prior to their TBI. Conclusions This work represents an important first step in understanding the special education services for students with TBI. Future research should explore interventions that are ecologically valid for school-based settings and are developed to address the idiosyncratic deficits of students with TBI, particularly interventions that focus on the underlying cognitive processes experienced by these students.

Considering Health Care Needs in a Rural Parkinson Disease Community.

BACKGROUND: People living with Parkinson disease (PD) have multiple health care needs that intensify over time, because the disease is both chronic and degenerative. Past research indicates that issues with mobility, financial constraints, and lack of support networks impede access to health care for people with PD. These challenges are elevated for individuals who live in rural communities due to the lack of local health care professionals and specialists and support resources, and the need to travel to see providers/specialists. The research objective was to have PD community stakeholders identify health care barriers and resources as well as possibilities for improved health care in a rural state. METHODS: Focus groups were conducted in the context of a community-based participatory research (CBPR) approach. Focus group data collection helped create comfort and parity in the discussion, while a CBPR approach allows for authenticity of the findings because members of the community in question are involved as researchers. The responses were recorded and transcribed verbatim. Coding and organizing of themes was completed manually and using NVIVO 10 software. RESULTS: Qualitative analysis revealed three main themes, PD issues, access issues, and stigma. These themes described disease-related stigma and concerns about disease progression and treatment, as well as challenges in accessing information, providers, and support by the PD stakeholders. The study results provided insight into the needs of people living with PD in rural communities. CONCLUSIONS: Rural PD stakeholders proposed the use of technology (e.g., telehealth) to provide support to improve health care for people with PD.

Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease.

Human T cells coordinate adaptive immunity in diverse anatomic compartments through production of cytokines and effector molecules, but it is unclear how tissue site influences T cell persistence and function. Here, we use single cell RNA-sequencing (scRNA-seq) to define the heterogeneity of human T cells isolated from lungs, lymph nodes, bone marrow and blood, and their functional responses following stimulation. Through analysis of >50,000 resting and activated T cells, we reveal tissue T cell signatures in mucosal and lymphoid sites, and lineage-specific activation states across all sites including distinct effector states for CD8+ T cells and an interferon-response state for CD4+ T cells. Comparing scRNA-seq profiles of tumor-associated T cells to our dataset reveals predominant activated CD8+ compared to CD4+ T cell states within multiple tumor types. Our results therefore establish a high dimensional reference map of human T cell activation in health for analyzing T cells in disease.

Speech-Language Pathologists' Comfort Providing Intervention to Children With Traumatic Brain Injury: Results From a National Survey.

Purpose This exploratory study examined speech-language pathologists' (SLPs) clinical experience and work environment characteristics impacting comfort with providing intervention to children with traumatic brain injury (TBI). Method This study included 162 SLPs who responded to a national survey about their comfort providing intervention to children with TBI, clinical experience (i.e., years of experience treating children with TBI, TBI preprofessional training and professional development, and licensure/credentialing), and work environment (i.e., work setting, caseload size, geographic location). Results Findings from latent class analysis revealed 3 distinct groups of SLPs based on their comfort with providing services to children with TBI: those with low comfort, moderate comfort, and high comfort. Further analyses revealed statistically significant differences across the 3 groups in the areas of years of experience treating children with TBI, professional development, work setting, TBI caseload size, and geographic location. Conclusions Our findings reveal that most SLPs feel comfortable providing intervention to children with TBI; however, differences in characteristics across groups suggest that specific steps can be taken to ensure increased comfort for all SLPs working with this population. Practicing SLPs may increase their level of comfort through professional development and hands-on, mentored experience with TBI. Efforts such as these may influence the quality of service provision and expand the population of SLPs who feel comfortable treating children with TBI. Future research is needed to further examine how comfort and SLP characteristics directly impact the quality of speech and language intervention and long-term outcomes of children with TBI.

Harnessing Hematopoietic Stem Cell Low Intracellular Calcium Improves Their Maintenance In Vitro.

The specific cellular physiology of hematopoietic stem cells (HSCs) is underexplored, and their maintenance in vitro remains challenging. We discovered that culture of HSCs in low calcium increased their maintenance as determined by phenotype, function, and single-cell expression signature. HSCs are endowed with low intracellular calcium conveyed by elevated activity of glycolysis-fueled plasma membrane calcium efflux pumps and a low-bone-marrow interstitial fluid calcium concentration. Low-calcium conditions inhibited calpain proteases, which target ten-eleven translocated (TET) enzymes, of which TET2 was required for the effect of low calcium conditions on HSC maintenance in vitro. These observations reveal a physiological feature of HSCs that can be harnessed to improve their maintenance in vitro.

Single cell RNA-Seq reveals pre-cDCs fate determined by transcription factor combinatorial dose.

BACKGROUND: Classic dendritic cells (cDCs) play a central role in the immune system by processing and presenting antigens to activate T cells, and consist of two major subsets: CD141+ cDC (cDC1) and CD1c+ cDC (cDC2). A population of migratory precursor cells, the pre-cDCs, is the immediate precursors to both cDC subsets. Previous studies showed that there were two pre-committed pre-cDC subpopulations. However, the key molecular drivers of pre-commitment in human pre-cDCs were not investigated. RESULTS: To identify the key molecular drivers for pre-commitment in human pre-cDCs, we performed single cell RNA sequencing (RNA-Seq) of two cDC subsets and pre-cDCs, and bulk RNA-Seq of pre-cDCs and cDCs from human peripheral blood. We found that pre-DC subpopulations cannot be separated by either variable genes within pre-cDCs or differentially expressed genes between cDC1 and cDC2. In contrast, they were separated by 16 transcription factors that are themselves differentially expressed or have regulated targets enriched in the differentially expressed genes between bulk cDC1 and cDC2, with one subpopulation close to cDC1 and the other close to cDC2. More importantly, these two pre-cDC sub-populations are correlated with ratio of IRF8 to IRF4 expression level more than their individual expression level. We also verified these findings using three recently published datasets. CONCLUSIONS: In this study, we demonstrate that single cell transcriptome profiling can reveal pre-cDCs differentiation map, and our results suggest the concept that combinatorial dose of transcription factors determines cell differentiation fate.

Using the OSU TBI-ID method for screening rural, older adults: a mixed methods feasibility study.

Objective: To examine the feasibility of: (1) a brain injury and screening tool (Ohio State University Traumatic Brain Injury Identification Method; OSU TBI-ID) training for rural Area Agency on Aging (AAA) health professionals, and (2) implementation of the screening process.  Research Design: A mixed methods design was utilized to assess several aspects of feasibility. Quantitatively, the researchers examined AAA health professionals' scores on a brain injury misconceptions survey, descriptive statistics about the clients screened, and health professionals' accuracy using the OSU TBI-ID. Qualitative data was collected via focus group interviews with the health professionals.  Methods and Procedures: The researchers conducted brain injury education and screening tool training for AAA health professionals. Subsequently, the health professionals used the OSU TBI-ID to screen their older adult clients for brain injury.  Main Outcomes and Results: AAA health professionals learned the OSU TBI-ID quickly and used the protocol correctly. The screening results established that 15% of the clients screened positive for brain injury; of those with positive screens, 87% did not have a previous brain injury diagnosis.  Conclusions: The current study presents evidence of feasibility for (1) training AAA health professionals, and (2) implementation of the OSU TBI-ID to screen older adult clients.

Generation and persistence of human tissue-resident memory T cells in lung transplantation.

Tissue-resident memory T cells (TRM) maintain immunity in diverse sites as determined in mouse models, whereas their establishment and role in human tissues have been difficult to assess. Here, we investigated human lung TRM generation, maintenance, and function in airway samples obtained longitudinally from human leukocyte antigen (HLA)-disparate lung transplant recipients, where donor and recipient T cells could be localized and tracked over time. Donor T cells persist specifically in the lungs (and not blood) of transplant recipients and express high levels of TRM signature markers including CD69, CD103, and CD49a, whereas lung-infiltrating recipient T cells gradually acquire TRM phenotypes over months in vivo. Single-cell transcriptome profiling of airway T cells reveals that donor T cells comprise two TRM-like subsets with varying levels of expression of TRM-associated genes, whereas recipient T cells comprised non-TRM and similar TRM-like subpopulations, suggesting de novo TRM generation. Transplant recipients exhibiting higher frequencies of persisting donor TRM experienced fewer adverse clinical events such as primary graft dysfunction and acute cellular rejection compared with recipients with low donor TRM persistence, suggesting that monitoring TRM dynamics could be clinically informative. Together, our results provide spatial and temporal insights into how human TRM develop, function, persist, and affect tissue integrity within the complexities of lung transplantation.

De novo gene signature identification from single-cell RNA-seq with hierarchical Poisson factorization.

Common approaches to gene signature discovery in single-cell RNA-sequencing (scRNA-seq) depend upon predefined structures like clusters or pseudo-temporal order, require prior normalization, or do not account for the sparsity of single-cell data. We present single-cell hierarchical Poisson factorization (scHPF), a Bayesian factorization method that adapts hierarchical Poisson factorization (Gopalan et al, 2015, Proceedings of the 31st Conference on Uncertainty in Artificial Intelligence, 326) for de novo discovery of both continuous and discrete expression patterns from scRNA-seq. scHPF does not require prior normalization and captures statistical properties of single-cell data better than other methods in benchmark datasets. Applied to scRNA-seq of the core and margin of a high-grade glioma, scHPF uncovers marked differences in the abundance of glioma subpopulations across tumor regions and regionally associated expression biases within glioma subpopulations. scHFP revealed an expression signature that was spatially biased toward the glioma-infiltrated margins and associated with inferior survival in glioblastoma.

Single-cell transcriptome analysis of lineage diversity in high-grade glioma.

BACKGROUND: Despite extensive molecular characterization, we lack a comprehensive understanding of lineage identity, differentiation, and proliferation in high-grade gliomas (HGGs). METHODS: We sampled the cellular milieu of HGGs by profiling dissociated human surgical specimens with a high-density microwell system for massively parallel single-cell RNA-Seq. We analyzed the resulting profiles to identify subpopulations of both HGG and microenvironmental cells and applied graph-based methods to infer structural features of the malignantly transformed populations. RESULTS: While HGG cells can resemble glia or even immature neurons and form branched lineage structures, mesenchymal transformation results in unstructured populations. Glioma cells in a subset of mesenchymal tumors lose their neural lineage identity, express inflammatory genes, and co-exist with marked myeloid infiltration, reminiscent of molecular interactions between glioma and immune cells established in animal models. Additionally, we discovered a tight coupling between lineage resemblance and proliferation among malignantly transformed cells. Glioma cells that resemble oligodendrocyte progenitors, which proliferate in the brain, are often found in the cell cycle. Conversely, glioma cells that resemble astrocytes, neuroblasts, and oligodendrocytes, which are non-proliferative in the brain, are generally non-cycling in tumors. CONCLUSIONS: These studies reveal a relationship between cellular identity and proliferation in HGG and distinct population structures that reflects the extent of neural and non-neural lineage resemblance among malignantly transformed cells.