scholarly journals The developing mouse coronal suture at single-cell resolution

2021 ◽  
Author(s):  
D'Juan Farmer ◽  
Hana Mlcochova ◽  
Yan Zhou ◽  
Nils Koelling ◽  
Guanlin Wang ◽  
...  
Keyword(s):  
Single Cell ◽  
Dura Mater ◽  
Cell Types ◽  
Coronal Suture ◽  
Cartilage Formation ◽  
Osteogenic Cells ◽  
Pathological Conditions ◽  
Coronal Synostosis ◽  
Parietal Bones ◽  
The Brain

Abstract Sutures separate the flat bones of the skull and enable coordinated growth of the brain and overlying cranium. To uncover the cellular diversity within sutures, we generated single-cell transcriptomes and performed extensive expression validation of the embryonic murine coronal suture. We identify Erg and Pthlh as markers of osteogenic progenitors in sutures, and distinct pre-osteoblast signatures between the bone fronts and periosteum. In the ectocranial layers above the suture, we observe a ligament-like population spanning the frontal and parietal bones. In the dura mater underlying the suture, we detect a chondrocyte-like signature potentially linked to cartilage formation under pathological conditions. Genes mutated in coronal synostosis are preferentially expressed in proliferative osteogenic cells, as well as meningeal layers, suggesting discrete cell types that may be altered in different syndromes. This single-cell atlas provides a resource for understanding development of the coronal suture, the suture most commonly fused in monogenic craniosynostosis.

scholarly journals The developing mouse coronal suture at single-cell resolution

2021 ◽  
Author(s):  
D’Juan T. Farmer ◽  
Hana Mlcochova ◽  
Yan Zhou ◽  
Nils Koelling ◽  
Guanlin Wang ◽  
...  
Keyword(s):  
Single Cell ◽  
Dura Mater ◽  
Cell Types ◽  
Coronal Suture ◽  
Cartilage Formation ◽  
Osteogenic Cells ◽  
Pathological Conditions ◽  
Coronal Synostosis ◽  
Parietal Bones ◽  
The Brain

AbstractSutures separate the flat bones of the skull and enable coordinated growth of the brain and overlying cranium. To uncover the cellular diversity within sutures, we generated single-cell transcriptomes and performed extensive expression validation of the embryonic murine coronal suture. We identify Erg and Pthlh as markers of osteogenic progenitors in sutures, and distinct pre-osteoblast signatures between the bone fronts and periosteum. In the ectocranial layers above the suture, we observe a ligament-like population spanning the frontal and parietal bones. In the dura mater underlying the suture, we detect a chondrocyte-like signature potentially linked to cartilage formation under pathological conditions. Genes mutated in coronal synostosis are preferentially expressed in proliferative osteogenic cells, as well as meningeal layers, suggesting discrete cell types that may be altered in different syndromes. This single-cell atlas provides a resource for understanding development of the coronal suture, the suture most commonly fused in monogenic craniosynostosis.

scholarly journals The developing mouse coronal suture at single-cell resolution

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
D’Juan T. Farmer ◽  
Hana Mlcochova ◽  
Yan Zhou ◽  
Nils Koelling ◽  
Guanlin Wang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Single Cell ◽  
Dura Mater ◽  
Lineage Tracing ◽  
Coronal Suture ◽  
The Brain

AbstractSutures separate the flat bones of the skull and enable coordinated growth of the brain and overlying cranium. The coronal suture is most commonly fused in monogenic craniosynostosis, yet the unique aspects of its development remain incompletely understood. To uncover the cellular diversity within the murine embryonic coronal suture, we generated single-cell transcriptomes and performed extensive expression validation. We find distinct pre-osteoblast signatures between the bone fronts and periosteum, a ligament-like population above the suture that persists into adulthood, and a chondrogenic-like population in the dura mater underlying the suture. Lineage tracing reveals an embryonic Six2+ osteoprogenitor population that contributes to the postnatal suture mesenchyme, with these progenitors being preferentially affected in a Twist1+/−; Tcf12+/− mouse model of Saethre-Chotzen Syndrome. This single-cell atlas provides a resource for understanding the development of the coronal suture and the mechanisms for its loss in craniosynostosis.

Study on Morphometric Features of Coronal Suture Along with it Absence and Craniosynostosis

2021 ◽  
Vol 9 (4) ◽  
pp. 8151-8155
Author(s):  
Khaleel N ◽  
◽  
Angadi A V ◽  
Muralidhar P S ◽  
Shabiya M ◽  
...  
Keyword(s):  
Birth Defect ◽  
Cranial Sutures ◽  
Coronal Suture ◽  
Cranial Suture ◽  
Medical Sciences ◽  
Hot Climate ◽  
Morphometric Features ◽  
Metopic Suture ◽  
Parietal Bones ◽  
The Brain

Background: Cranial sutures are syndesmosis between the cranial bones. The coronal suture is oblique in direction and extends between the frontal and the parietal bones. Craniosynostosis is a rare birth defect that occurs when the coronal suture in the skull fuses prematurely, but the brain continues to grow and develop. This leads to a misshapen head. There are a number of forms of this defect, such as coronal, sagittal, lambdoid, and metopic. Materials and Methods: Total 500 skulls were used for study, coronal suture length measured by thread method, distance between Nasion to bregma and midsupraorbital rim to coronal suture were measured. For finding skull with absence of coronal, sagittal, lambdoid, and metopic suture, we examined many skulls during routine osteology classes of Medical, Dental and other medical sciences students. Around 500 skull observed and we find only one skull with absence of left coronal suture completely. Results: The length of coronal suture was 24.8+1.4cm length, the distance between nasion to bregma was 126.7 +10.25 mm and Midsupraorbital rim to cranial suture was 102.76+8.64mm We have found only one skull with absence of coronal suture. Some of the skulls shows partly fusion of sagittal, coronal sutures. The skull with complete absence of coronal suture showing the features of other sutures clearly and right side of coronal suture is showing the complete suture. The skull was not damaged and it is in perfect condition which was using by students for their osteology study. Conclusion: We found the skull with absence of left coronal suture, which may resulted due to craniosynostosis. It may be due to hot climate in India also might be resulted for absence of suture. KEY WORDS: Birth defect, Skull, Coronal suture, Craniosynostosis.

scholarly journals STAB: a spatio-temporal cell atlas of the human brain

2020 ◽  
Vol 49 (D1) ◽  
pp. D1029-D1037
Author(s):  
Liting Song ◽  
Shaojun Pan ◽  
Zichao Zhang ◽  
Longhao Jia ◽  
Wei-Hua Chen ◽  
...  
Keyword(s):  
Human Brain ◽  
Single Cell ◽  
Temporal Dynamics ◽  
Cell Types ◽  
Brain Regions ◽  
Molecular Characteristics ◽  
Great Effort ◽  
Brain Functions ◽  
Spatio Temporal ◽  
The Brain

Abstract The human brain is the most complex organ consisting of billions of neuronal and non-neuronal cells that are organized into distinct anatomical and functional regions. Elucidating the cellular and transcriptome architecture underlying the brain is crucial for understanding brain functions and brain disorders. Thanks to the single-cell RNA sequencing technologies, it is becoming possible to dissect the cellular compositions of the brain. Although great effort has been made to explore the transcriptome architecture of the human brain, a comprehensive database with dynamic cellular compositions and molecular characteristics of the human brain during the lifespan is still not available. Here, we present STAB (a Spatio-Temporal cell Atlas of the human Brain), a database consists of single-cell transcriptomes across multiple brain regions and developmental periods. Right now, STAB contains single-cell gene expression profiling of 42 cell subtypes across 20 brain regions and 11 developmental periods. With STAB, the landscape of cell types and their regional heterogeneity and temporal dynamics across the human brain can be clearly seen, which can help to understand both the development of the normal human brain and the etiology of neuropsychiatric disorders. STAB is available at http://stab.comp-sysbio.org.

scholarly journals Molecular identification of sixty-three amacrine cell types completes a mouse retinal cell atlas

2020 ◽  
Author(s):  
Wenjun Yan ◽  
Mallory A. Laboulaye ◽  
Nicholas M. Tran ◽  
Irene E. Whitney ◽  
Inbal Benhar ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Single Cell ◽  
High Throughput ◽  
Amacrine Cells ◽  
Cell Types ◽  
Retinal Cell ◽  
Mouse Retina ◽  
Single Cell Rna Sequencing ◽  
Neuronal Types ◽  
The Brain

ABSTRACTAmacrine cells (ACs) are a diverse class of interneurons that modulate input from photoreceptors to retinal ganglion cells (RGCs), rendering each RGC type selectively sensitive to particular visual features, which are then relayed to the brain. While many AC types have been identified morphologically and physiologically, they have not been comprehensively classified or molecularly characterized. We used high-throughput single-cell RNA sequencing (scRNA-seq) to profile >32,000 ACs from mouse retina, and applied computational methods to identify 63 AC types. We identified molecular markers for each type, and used them to characterize the morphology of multiple types. We show that they include nearly all previously known AC types as well as many that had not been described. Consistent with previous studies, most of the AC types express markers for the canonical inhibitory neurotransmitters GABA or glycine, but several express neither or both. In addition, many express one or more neuropeptides, and two express glutamatergic markers. We also explored transcriptomic relationships among AC types and identified transcription factors expressed by individual or multiple closely related types. Noteworthy among these were Meis2 and Tcf4, expressed by most GABAergic and most glycinergic types, respectively. Together, these results provide a foundation for developmental and functional studies of ACs, as well as means for genetically accessing them. Along with previous molecular, physiological and morphological analyses, they establish the existence of at least 130 neuronal types and nearly 140 cell types in mouse retina.SIGNIFICANCE STATEMENTThe mouse retina is a leading model for analyzing the development, structure, function and pathology of neural circuits. A complete molecular atlas of retinal cell types provides an important foundation for these studies. We used high-throughput single-cell RNA sequencing (scRNA-seq) to characterize the most heterogeneous class of retinal interneurons, amacrine cells, identifying 63 distinct types. The atlas includes types identified previously as well as many novel types. We provide evidence for use of multiple neurotransmitters and neuropeptides and identify transcription factors expressed by groups of closely related types. Combining these results with those obtained previously, we proposed that the mouse retina contains 130 neuronal types, and is therefore comparable in complexity to other regions of the brain.

scholarly journals Multi-modal single cell analysis reveals brain immune landscape plasticity during aging and gut microbiota dysbiosis

2020 ◽  
Author(s):  
Samantha M. Golomb ◽  
Ian H. Guldner ◽  
Anqi Zhao ◽  
Qingfei Wang ◽  
Bhavana Palakurthi ◽  
...  
Keyword(s):  
Single Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Cell Plasticity ◽  
Tissue Microenvironment ◽  
Gut Dysbiosis ◽  
Resolution Single ◽  
The Brain ◽  
Gut Microbiota Dysbiosis

ABSTRACTThe brain contains a diverse array of immune cell types. The phenotypic and functional plasticity of brain immune cells collectively contribute to brain tissue homeostasis and disease progression. Immune cell plasticity is profoundly influenced by local tissue microenvironment cues and systemic factors. Yet, the transcriptional mechanism by which systemic stimuli, such as aging and gut microbiota dysbiosis, reshape brain immune cell plasticity and homeostasis has not been fully delineated. Using Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq), we analyzed compositional and transcriptional changes of the brain immune landscape in response to aging and gut dysbiosis. We first examined the discordance between canonical surface marker-defined immune cell types (Cell-ID) and their transcriptome signatures, which suggested transcriptional plasticity among immune cells despite sharing the same cell surface markers. Specifically, inflammatory and patrolling Ly6C+ monocytes were shifted predominantly to a pro-inflammatory transcriptional program in the aged brain, while brain ILCs shifted toward an ILC2 transcriptional profile. Finally, aging led to an increase of ILC-like cells expressing a T memory stemness (Tscm) signature in the brain. Antibiotics (ABX)-induced gut dysbiosis reduced the frequency of ILCs exhibiting Tscm-like properties in the aged mice, but not in the young mice. Enabled by high-resolution single-cell molecular phenotyping, our study revealed that systemic changes due to aging and gut dysbiosis prime the brain environment for an increased propensity for neuroinflammation, which provided insights into gut dysbiosis in age-related neurological diseases.Manuscript SummaryGolomb et al. performed Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq) on immune cells from the brains of young and aged mice with and without antibiotics-induced gut dysbiosis. High resolution, single cell immunophenotyping enabled the dissection of extensive transcriptional plasticity of canonically identified monocytes and innate lymphoid cells (ILCs) in the aged brain. Through differential gene expression and trajectory inference analyses, the authors revealed tissue microenvironment-dependent cellular responses influenced by aging and gut dysbiosis that may potentiate neuroinflammatory diseases.Graphical Abstract

scholarly journals Meta-Analysis of cortical inhibitory interneurons markers landscape and their performances in scRNA-seq studies.

2021 ◽  
Author(s):  
Lorenzo Martini ◽  
Roberta Bardini ◽  
Stefano Di Carlo
Keyword(s):  
Single Cell ◽  
Meta Analysis ◽  
Cell Types ◽  
Cellular Heterogeneity ◽  
Marker Genes ◽  
Inhibitory Interneurons ◽  
Rna Seq ◽  
Circuit Function ◽  
The Brain

The mammalian cortex contains a great variety of neuronal cells. In particular, GABAergic interneurons, which play a major role in neuronal circuit function, exhibit an extraordinary diversity of cell types. In this regard, single-cell RNA-seq analysis is crucial to study cellular heterogeneity. To identify and analyze rare cell types, it is necessary to reliably label cells through known markers. In this way, all the related studies are dependent on the quality of the employed marker genes. Therefore, in this work, we investigate how a set of chosen inhibitory interneurons markers perform. The gene set consists of both immunohistochemistry-derived genes and single-cell RNA-seq taxonomy ones. We employed various human and mouse datasets of the brain cortex, consequently processed with the Monocle3 pipeline. We defined metrics based on the relations between unsupervised cluster results and the marker expression. Specifically, we calculated the specificity, the fraction of cells expressing, and some metrics derived from decision tree analysis like entropy gain and impurity reduction. The results highlighted the strong reliability of some markers but also the low quality of others. More interestingly, though, a correlation emerges between the general performances of the genes set and the experimental quality of the datasets. Therefore, the proposed method allows evaluating the quality of a dataset in relation to its reliability regarding the inhibitory interneurons cellular heterogeneity study.

scholarly journals Single-cell analysis identifies a key role for Hhip in murine coronal suture development

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Greg Holmes ◽  
Ana S. Gonzalez-Reiche ◽  
Madrikha Saturne ◽  
Susan M. Motch Perrine ◽  
Xianxiao Zhou ◽  
...  
Keyword(s):  
Single Cell ◽  
Hedgehog Signaling ◽  
Bone Growth ◽  
Single Cell Analysis ◽  
Coronal Suture ◽  
Cell Analysis ◽  
Rna Seq ◽  
Wild Type ◽  
Calvarial Bone ◽  
Osteogenic Cells

AbstractCraniofacial development depends on formation and maintenance of sutures between bones of the skull. In sutures, growth occurs at osteogenic fronts along the edge of each bone, and suture mesenchyme separates adjacent bones. Here, we perform single-cell RNA-seq analysis of the embryonic, wild type murine coronal suture to define its population structure. Seven populations at E16.5 and nine at E18.5 comprise the suture mesenchyme, osteogenic cells, and associated populations. Expression of Hhip, an inhibitor of hedgehog signaling, marks a mesenchymal population distinct from those of other neurocranial sutures. Tracing of the neonatal Hhip-expressing population shows that descendant cells persist in the coronal suture and contribute to calvarial bone growth. In Hhip−/− coronal sutures at E18.5, the osteogenic fronts are closely apposed and the suture mesenchyme is depleted with increased hedgehog signaling compared to those of the wild type. Collectively, these data demonstrate that Hhip is required for normal coronal suture development.

scholarly journals Brain Microenvironment Heterogeneity: Potential Value for Brain Tumors

2021 ◽  
Vol 11 ◽  
Author(s):  
Laura Álvaro-Espinosa ◽  
Ana de Pablos-Aragoneses ◽  
Manuel Valiente ◽  
Neibla Priego
Keyword(s):  
Brain Tumors ◽  
Single Cell ◽  
Brain Injuries ◽  
Clinical Work ◽  
Cell Types ◽  
Brain Cell ◽  
Brain Disorders ◽  
Brain Connectome ◽  
The Brain ◽  
Brain Cell Types

Uncovering the complexity of the microenvironment that emerges in brain disorders is key to identify potential vulnerabilities that might help challenging diseases affecting this organ. Recently, genomic and proteomic analyses, especially at the single cell level, have reported previously unrecognized diversity within brain cell types. The complexity of the brain microenvironment increases during disease partly due to the immune infiltration from the periphery that contributes to redefine the brain connectome by establishing a new crosstalk with resident brain cell types. Within the rewired brain ecosystem, glial cell subpopulations are emerging hubs modulating the dialogue between the Immune System and the Central Nervous System with important consequences in the progression of brain tumors and other disorders. Single cell technologies are crucial not only to define and track the origin of disease-associated cell types, but also to identify their molecular similarities and differences that might be linked to specific brain injuries. These altered molecular patterns derived from reprogramming the healthy brain into an injured organ, might provide a new generation of therapeutic targets to challenge highly prevalent and lethal brain disorders that remain incurable with unprecedented specificity and limited toxicities. In this perspective, we present the most relevant clinical and pre-clinical work regarding the characterization of the heterogeneity within different components of the microenvironment in the healthy and injured brain with a special interest on single cell analysis. Finally, we discuss how understanding the diversity of the brain microenvironment could be exploited for translational purposes, particularly in primary and secondary tumors affecting the brain.

scholarly journals Single-cell analysis identifies a key role forHhipin murine coronal suture development

2021 ◽  
Author(s):  
Greg Holmes ◽  
Ana S. Gonzalez-Reiche ◽  
Madrikha Saturne ◽  
Xianxiao Zhou ◽  
Ana C. Borges ◽  
...  
Keyword(s):  
Single Cell ◽  
Hedgehog Signaling ◽  
Bone Growth ◽  
Single Cell Analysis ◽  
Abnormal Development ◽  
Integrated Analysis ◽  
Coronal Suture ◽  
Rna Seq ◽  
Osteogenic Cells ◽  
Insight Into

AbstractCraniofacial development depends on proper formation and maintenance of sutures between adjacent bones of the skull. In sutures, bone growth occurs at the edge of each bone, and suture mesenchyme maintains the separation between them. We performed single-cell RNA-seq analyses of the embryonic, murine coronal suture. Analyzing replicate libraries at E16.5 and E18.5, we identified 14 cell populations. Seven populations at E16.5 and nine at E18.5 comprised the suture mesenchyme, osteogenic cells, and associated populations. Through an integrated analysis with bulk RNA-seq data, we found a distinct coronal suture mesenchyme population compared to other neurocranial sutures, marked by expression ofHhip, an inhibitor of hedgehog signaling. We found that at E18.5,Hhip-/-coronal osteogenic fronts are closely apposed and suture mesenchyme is depleted, demonstrating thatHhipis required for coronal suture development. Our transcriptomic approach provides a rich resource for insight into normal and abnormal development.

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