scholarly journals Single-Cell Transcriptional Profiling Reveals Cellular Diversity and Intercommunication in the Mouse Heart

Cell Reports ◽  
2018 ◽  
Vol 22 (3) ◽  
pp. 600-610 ◽  
Author(s):  
Daniel A. Skelly ◽  
Galen T. Squiers ◽  
Micheal A. McLellan ◽  
Mohan T. Bolisetty ◽  
Paul Robson ◽  
...  
Keyword(s):  
Single Cell ◽  
Transcriptional Profiling ◽  
Mouse Heart

scholarly journals Single cell transcriptional profiling reveals cellular diversity, communication, and sexual dimorphism in the mouse heart

2017 ◽  
Author(s):  
Daniel A. Skelly ◽  
Galen T. Squiers ◽  
Micheal A. McLellan ◽  
Mohan T. Bolisetty ◽  
Paul Robson ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Single Cell ◽  
Cell Biology ◽  
Immune Cell ◽  
Cardiac Development ◽  
Transcriptional Profiling ◽  
Cell Populations ◽  
Mouse Heart ◽  
Cardiac Cell ◽  
Immune Sensing

INTRODUCTORY PARAGRAPHCharacterization of the cardiac cellulome—the network of cells that form the heart—is essential for understanding cardiac development and normal organ function, and for formulating precise therapeutic strategies to combat heart disease. Recent studies have challenged assumptions about both the cellular composition1 and functional significance of the cardiac non-myocyte cell pool, with unexpected roles identified for resident fibroblasts2 and immune cell populations3,4. In this study, we characterized single-cell transcriptional profiles of the murine non-myocyte cardiac cellular landscape using single-cell RNA sequencing (scRNA-Seq). Detailed molecular analyses revealed the diversity of the cardiac cellulome and facilitated the development of novel techniques to isolate understudied cardiac cell populations such as mural cells and glia. Our analyses also revealed networks of intercellular communication as well as extensive sexual dimorphism in gene expression in the heart, most notably demonstrated by the upregulation of immune-sensing and pro-inflammatory genes in male cardiac macrophages. This study offers new insights into the structure and function of the mammalian cardiac cellulome and provides an important resource that will stimulate new studies in cardiac cell biology.

scholarly journals Integrating readout of somatic mutations in individual cells with single-cell transcriptional profiling

2021 ◽  
Vol 2 (3) ◽  
pp. 100673
Author(s):  
Shichen Liu ◽  
Maximilian Nguyen ◽  
Sahand Hormoz
Keyword(s):  
Single Cell ◽  
Somatic Mutations ◽  
Transcriptional Profiling

scholarly journals Spatially defined single-cell transcriptional profiling characterizes diverse chondrocyte subtypes and nucleus pulposus progenitors in human intervertebral discs

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Yibo Gan ◽  
Jian He ◽  
Jun Zhu ◽  
Zhengyang Xu ◽  
Zhong Wang ◽  
...  
Keyword(s):  
Single Cell ◽  
Nucleus Pulposus ◽  
Molecular Mechanisms ◽  
Transcriptional Profiling ◽  
Intervertebral Discs ◽  
Cellular Heterogeneity ◽  
Effector Functions ◽  
Cartilage Endplate ◽  
Intervertebral Disks ◽  
Ivd Degeneration

AbstractA comprehensive understanding of the cellular heterogeneity and molecular mechanisms underlying the development, homeostasis, and disease of human intervertebral disks (IVDs) remains challenging. Here, the transcriptomic landscape of 108 108 IVD cells was mapped using single-cell RNA sequencing of three main compartments from young and adult healthy IVDs, including the nucleus pulposus (NP), annulus fibrosus, and cartilage endplate (CEP). The chondrocyte subclusters were classified based on their potential regulatory, homeostatic, and effector functions in extracellular matrix (ECM) homeostasis. Notably, in the NP, a PROCR+ resident progenitor population showed enriched colony-forming unit-fibroblast (CFU-F) activity and trilineage differentiation capacity. Finally, intercellular crosstalk based on signaling network analysis uncovered that the PDGF and TGF-β cascades are important cues in the NP microenvironment. In conclusion, a single-cell transcriptomic atlas that resolves spatially regulated cellular heterogeneity together with the critical signaling that underlies homeostasis will help to establish new therapeutic strategies for IVD degeneration in the clinic.

scholarly journals Probing Plasmodium falciparum sexual commitment at the single-cell level

2018 ◽  
Vol 3 ◽  
pp. 70 ◽  
Author(s):  
Nicolas M.B. Brancucci ◽  
Mariana De Niz ◽  
Timothy J. Straub ◽  
Deepali Ravel ◽  
Lauriane Sollelis ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Single Cell ◽  
Transcriptional Profiling ◽  
Quantitative Imaging ◽  
Complex Life Cycle ◽  
Major Transitions ◽  
Transcriptional Signature ◽  
Life Cycle Stages ◽  
Parasite Populations

Background: Malaria parasites go through major transitions during their complex life cycle, yet the underlying differentiation pathways remain obscure. Here we apply single cell transcriptomics to unravel the program inducing sexual differentiation in Plasmodium falciparum. Parasites have to make this essential life-cycle decision in preparation for human-to-mosquito transmission. Methods: By combining transcriptional profiling with quantitative imaging and genetics, we defined a transcriptional signature in sexually committed cells. Results: We found this transcriptional signature to be distinct from general changes in parasite metabolism that can be observed in response to commitment-inducing conditions. Conclusions: This proof-of-concept study provides a template to capture transcriptional diversity in parasite populations containing complex mixtures of different life-cycle stages and developmental programs, with important implications for our understanding of parasite biology and the ongoing malaria elimination campaign.

scholarly journals Single-Cell RNA-Sequencing Identifies Infrapatellar Fat Pad Macrophage Polarization in Acute Synovitis/Fat Pad Fibrosis and Cell Therapy

2021 ◽  
Vol 8 (11) ◽  
pp. 166
Author(s):  
Dimitrios Kouroupis ◽  
Thomas M. Best ◽  
Lee D. Kaplan ◽  
Diego Correa ◽  
Anthony J. Griswold
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Transcriptional Profiling ◽  
Macrophage Polarization ◽  
Myeloid Cells ◽  
Cellular Heterogeneity ◽  
Joint Disease ◽  
Infrapatellar Fat Pad ◽  
Fat Pad ◽  
Single Cell Rna Sequencing

The pathogenesis and progression of knee inflammatory pathologies is modulated partly by residing macrophages in the infrapatellar fat pad (IFP), thus, macrophage polarization towards pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes is important in joint disease pathologies. Alteration of M1/M2 balance contributes to the initiation and progression of joint inflammation and can be potentially altered with mesenchymal stem cell (MSC) therapy. In an acute synovial/IFP inflammation rat model a single intra-articular injection of IFP-MSC was performed, having as controls (1) diseased rats not receiving IFP-MSC and (2) non-diseased rats. After 4 days, cell specific transcriptional profiling via single-cell RNA-sequencing was performed on isolated IFP tissue from each group. Eight transcriptomically distinct cell populations were identified within the IFP across all three treatment groups with a noted difference in the proportion of myeloid cells across the groups. Largely myeloid cells consisted of macrophages (>90%); one M1 sub-cluster highly expressing pro-inflammatory markers and two M2 sub-clusters with one of them expressing higher levels of canonical M2 markers. Notably, the diseased samples (11.9%) had the lowest proportion of cells expressing M2 markers relative to healthy (14.8%) and MSC treated (19.4%) samples. These results suggest a phenotypic polarization of IFP macrophages towards the pro-inflammatory M1 phenotype in an acute model of inflammation, which are alleviated by IFP-MSC therapy inducing a switch towards an alternate M2 status. Understanding the IFP cellular heterogeneity and associated transcriptional programs may offer insights into novel therapeutic strategies for disabling joint disease pathologies.

scholarly journals Spatial and Single-Cell Transcriptional Profiling Identifies Functionally Distinct Human Dermal Fibroblast Subpopulations

2018 ◽  
Vol 138 (4) ◽  
pp. 811-825 ◽  
Author(s):  
Christina Philippeos ◽  
Stephanie B. Telerman ◽  
Bénédicte Oulès ◽  
Angela O. Pisco ◽  
Tanya J. Shaw ◽  
...  
Keyword(s):  
Single Cell ◽  
Dermal Fibroblast ◽  
Transcriptional Profiling ◽  
Human Dermal Fibroblast

Age-Dependent Transcriptional Alterations in Cardiac Endothelial Cells

2021 ◽  
Author(s):  
Uchenna Emechebe ◽  
Jonathan William Nelson ◽  
Nabil J. Alkayed ◽  
Sanjiv Kaul ◽  
Andrew C Adey ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Single Cell ◽  
Significant Risk ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Mouse Heart ◽  
Age Related ◽  
Organ Systems ◽  
Transcriptional Alterations

Aging is a significant risk factor for cardiovascular disease. Despite the fact that endothelial cells play critical roles in cardiovascular function and disease, the molecular impact of aging on this cell population in many organ systems remains unknown. In this study, we sought to determine age-associated transcriptional alterations in cardiac endothelial cells. Highly enriched populations of endothelial cells (ECs) isolated from the heart, brain and kidney of young (3 months) and aged (24 months) C57/BL6 mice were profiled for RNA expression via bulk RNA sequencing. Approximately 700 cardiac endothelial transcripts significantly differ by age. Gene set enrichment analysis indicated similar patterns for cellular pathway perturbations. Receptor-ligand comparisons indicated parallel alterations in age-affected circulating factors and cardiac endothelial-expressed receptors. Single-cell RNA-seq analysis identified 9 distinct endothelial cell subtypes in the heart with an age-associated population shift observed for the Aplnr-enriched endothelial cell clusters. Gene and pathway enrichment analyses show that age-related transcriptional response of cardiac endothelial cells is distinct from that of endothelial cells derived from the brain or kidney vascular bed. Furthermore, single-cell analysis identified 9 distinct EC subtypes, and shows that the Aplnr-enriched subtype is reduced with age in mouse heart. Finally, we identify age-dysregulated genes in specific aged cardiac endothelial subtypes.

scholarly journals Transcribing the heart: faithfully interpreting cardiac transcriptional insights

2019 ◽  
Vol 14 (9) ◽  
pp. 805-810
Author(s):  
Oscar Echeagaray ◽  
Mark A Sussman
Keyword(s):  
Regenerative Medicine ◽  
Single Cell ◽  
Transcriptional Profiling ◽  
Bioinformatic Analysis ◽  
Therapeutic Approaches ◽  
Improve Efficiency ◽  
Accurate Interpretation ◽  
Bioinformatic Approaches ◽  
Selection Of

Transcriptional profiling continues to produce phenotypical data essential for understanding of basic cardiac biology and required to improve efficiency of cardiac regenerative and therapeutic approaches after injury. Accurate interpretation of cardiac transcriptional data comes with the unique challenges of heart biology including cardiomyocyte morphology, cryopreservation of limited samples and adequate selection of transcriptional platform at a single-cell resolution. Consequently, development and implementation of novel transcriptional platforms and creative bioinformatic analysis are essential to resolve standing questions in the field of cardiac regenerative medicine. Targeted bioinformatic approaches, advancing technological access, increase technical availability and fostering communication between interdisciplinary groups is critical to improve therapeutic approaches and to overcome challenges inherent to transcriptomic cardiac research.

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