17 research outputs found

    A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex.

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    Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain1-3. With the proliferation of multi-omics datasets, a major challenge is to validate and integrate results into a biological understanding of cell-type organization. Here we generated transcriptomes and epigenomes from more than 500,000 individual cells in the mouse primary motor cortex, a structure that has an evolutionarily conserved role in locomotion. We developed computational and statistical methods to integrate multimodal data and quantitatively validate cell-type reproducibility. The resulting reference atlas-containing over 56 neuronal cell types that are highly replicable across analysis methods, sequencing technologies and modalities-is a comprehensive molecular and genomic account of the diverse neuronal and non-neuronal cell types in the mouse primary motor cortex. The atlas includes a population of excitatory neurons that resemble pyramidal cells in layer 4 in other cortical regions4. We further discovered thousands of concordant marker genes and gene regulatory elements for these cell types. Our results highlight the complex molecular regulation of cell types in the brain and will directly enable the design of reagents to target specific cell types in the mouse primary motor cortex for functional analysis

    A multimodal cell census and atlas of the mammalian primary motor cortex

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    ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

    Impact of the mental health and dynamic referral for oncology (MHADRO) program on oncology patient outcomes, health care utilization, and health provider behaviors: A multi-site randomized control trial

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    OBJECTIVE: The MHADRO assesses psychosocial and medical needs, provides tailored feedback reports, and connects patients to mental health providers. This study examined the MHADRO\u27s effect on patient outcomes, health care utilization, and oncology provider documentation and behaviors. METHODS: 836 patients were part of a multi-site RCT and assessments were conducted at baseline, 2, 6 and 12 months. RESULTS: The intervention group engaged in less emergency calls to providers. There were no differences in psychosocial outcomes at follow up assessments. Providers of patients in the intervention group were more likely to: document psychosocial symptoms and history; refer to psychosocial services; encourage support groups; seek psychological evaluations during visits. Patients who agreed to a mental health referral had decreased hospitalizations, increased mental health care interactions, and stronger ratings of counseling potential benefits. This group also reported increased psychosocial distress at all follow-up assessments. CONCLUSION: The MHADRO may increase access to mental health care, lessen utilization, and improve providers\u27 management of psychosocial needs, but does not appear to impact overall functioning over time. PRACTICE IMPLICATIONS: Providers are encouraged to consider incorporating programs, like the MHADRO, into patient care as they may have the potential to impact screening and management of patients\u27 psychosocial needs
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