Single-cell atlas reveals meningeal leukocyte heterogeneity in the developing mouse brain
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ABSTRACT:
PROVIDER: PRJNA726986 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14408100_1.fastq.gz | Fastqsanger.gz | |||
| SRR14408100_2.fastq.gz | Fastqsanger.gz | |||
| SRR14408101_1.fastq.gz | Fastqsanger.gz | |||
| SRR14408101_2.fastq.gz | Fastqsanger.gz | |||
| SRR14408102_1.fastq.gz | Fastqsanger.gz |
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Project description:The meninges are important for brain development and pathology. Using single-cell RNA sequencing, we have generated the first comprehensive transcriptional atlas of neonatal mouse meningeal leukocytes under normal conditions and after perinatal brain injury. We identified almost all known leukocyte subtypes and found differences between neonatal and adult border-associated macrophages, thus highlighting that neonatal border-associated macrophages are functionally immature with regards to immune responses compared with their adult counterparts. We also identified novel meningeal microglia-like cell populations that may participate in white matter development. Early after the hypoxic-ischemic insult, neutrophil numbers increased and they exhibited increased granulopoiesis, suggesting that the meninges are an important site of immune cell expansion with implications for the initiation of inflammatory cascades after neonatal brain injury. Our study provides a single-cell resolution view of the importance of meningeal leukocytes at the early stage of development in health and disease.
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Project description:The meninges are a multilayered structure composed of fibroblasts, blood and lymphatic vessels, and immune cells. Meningeal fibroblasts secrete a variety of factors that control CNS development, yet strikingly little is known about their heterogeneity or development. Using single cell sequencing, we report distinct transcriptional signatures for fibroblasts in the embryonic dura, arachnoid and pial. We define new markers for meningeal layers and show conservation in human meninges. We find that embryonic meningeal fibroblasts are transcriptionally distinct between brain regions and identify a regionally localized pial sub-population marked by expression of µ-Crystallin. Developmental analysis reveals a progressive, ventral to dorsal maturation of telencephalic meninges. Our studies present an unprecedented view of meningeal fibroblasts, providing a molecular profile of embryonic meningeal fibroblasts by layer that yield insights into mechanisms of meninges development and function.
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Project description:The mammalian telencephalon plays critical roles in cognition, motor function, and emotion. While many of the genes required for its development have been identified, the distant‐acting regulatory sequences orchestrating their in vivo expression are mostly unknown. Here we describe a digital atlas of in vivo enhancers active in subregions of the developing telencephalon. We identified over 4,600 candidate embryonic forebrain enhancers and studied the in vivo activity of 329 of these sequences in transgenic mouse embryos. We generated serial sets of histological brain sections for 145 reproducible forebrain enhancers, resulting in a publicly accessible web‐based enhancer atlas comprising over 33,000 sections. We show how this large collection of annotated telencephalon enhancers can be used to study the regulatory architecture of individual genes, to examine the sequence motif content of enhancers, and to drive targeted reporter or effector protein expression in experimental applications. Furthermore, we used epigenomic analysis of human and mouse cortex tissue to directly compare the genome‐wide enhancer architecture in these species. This atlas provides a primary resource for investigating gene regulatory mechanisms of telencephalon development and enables studies of the role of distant‐acting enhancers in neurodevelopmental disorders. Examination of p300 binding in mouse embryonic stage 11.5 forebrain, mouse postnatal (P0) cortex tissue and human fetal (gestational week 20) cortex
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