scholarly journals Single cell sequencing analysis of lizard phagocytic cell populations and their role in tail regeneration

2020 ◽  
Vol 8 ◽  
pp. 100029
Author(s):  
Ricardo Londono ◽  
Sean Tighe ◽  
Beatrice Milnes ◽  
Christian DeMoya ◽  
Lina Maria Quijano ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Populations ◽  
Sequencing Analysis ◽  
Phagocytic Cell ◽  
Tail Regeneration ◽  
Single Cell Sequencing

scholarly journals Single-Cell Sequencing: Biological Insight and Potential Clinical Implications in Pediatric Leukemia

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5658
Author(s):  
Donát Alpár ◽  
Bálint Egyed ◽  
Csaba Bödör ◽  
Gábor T. Kovács
Keyword(s):  
High Resolution ◽  
Single Cell ◽  
Childhood Leukemia ◽  
Clinical Decision Making ◽  
Cellular Heterogeneity ◽  
Therapeutic Interventions ◽  
Cell Populations ◽  
Pediatric Leukemia ◽  
Single Cell Sequencing ◽  
Wide Range

Single-cell sequencing (SCS) provides high-resolution insight into the genomic, epigenomic, and transcriptomic landscape of oncohematological malignancies including pediatric leukemia, the most common type of childhood cancer. Besides broadening our biological understanding of cellular heterogeneity, sub-clonal architecture, and regulatory network of tumor cell populations, SCS can offer clinically relevant, detailed characterization of distinct compartments affected by leukemia and identify therapeutically exploitable vulnerabilities. In this review, we provide an overview of SCS studies focused on the high-resolution genomic and transcriptomic scrutiny of pediatric leukemia. Our aim is to investigate and summarize how different layers of single-cell omics approaches can expectedly support clinical decision making in the future. Although the clinical management of pediatric leukemia underwent a spectacular improvement during the past decades, resistant disease is a major cause of therapy failure. Currently, only a small proportion of childhood leukemia patients benefit from genomics-driven therapy, as 15–20% of them meet the indication criteria of on-label targeted agents, and their overall response rate falls in a relatively wide range (40–85%). The in-depth scrutiny of various cell populations influencing the development, progression, and treatment resistance of different disease subtypes can potentially uncover a wider range of driver mechanisms for innovative therapeutic interventions.

scholarly journals Using single-cell sequencing technology to detect circulating tumor cells in solid tumors

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jiasheng Xu ◽  
Kaili Liao ◽  
Xi Yang ◽  
Chengfeng Wu ◽  
Wei Wu ◽  
...  
Keyword(s):  
Single Cell ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
High Throughput Sequencing ◽  
Metastatic Potential ◽  
Sequencing Analysis ◽  
Sequencing Technology ◽  
Single Cell Sequencing

AbstractCirculating tumor cells are tumor cells with high vitality and high metastatic potential that invade and shed into the peripheral blood from primary solid tumors or metastatic foci. Due to the heterogeneity of tumors, it is difficult for high-throughput sequencing analysis of tumor tissues to find the genomic characteristics of low-abundance tumor stem cells. Single-cell sequencing of circulating tumor cells avoids interference from tumor heterogeneity by comparing the differences between single-cell genomes, transcriptomes, and epigenetic groups among circulating tumor cells, primary and metastatic tumors, and metastatic lymph nodes in patients' peripheral blood, providing a new perspective for understanding the biological process of tumors. This article describes the identification, biological characteristics, and single-cell genome-wide variation in circulating tumor cells and summarizes the application of single-cell sequencing technology to tumor typing, metastasis analysis, progression detection, and adjuvant therapy.

#71: Single-cell RNA Sequencing Analysis of Zika Virus Infection in Human Stem Cell-Derived Neuroprogenitor Cells and Cerebral Organoids

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S14-S14
Author(s):  
K E Ocwieja ◽  
T K Hughes ◽  
J M Antonucci ◽  
A L Richards ◽  
A C Stanton ◽  
...  
Keyword(s):  
Stem Cell ◽  
Single Cell ◽  
Rna Sequencing ◽  
Zika Virus ◽  
Molecular Mechanisms ◽  
Sequencing Analysis ◽  
Human Stem Cell ◽  
Zikv Infection ◽  
Single Cell Sequencing ◽  
Single Cell Rna Sequencing

Abstract Background The molecular mechanisms underpinning the neurologic and congenital pathologies caused by Zika virus (ZIKV) infection remain poorly understood. It is also unclear why congenital ZIKV disease was not observed prior to the recent epidemics in French Polynesia and the Americas, despite evidence that the Zika virus has actively circulated in parts of Africa and Asia since 1947 and 1966, respectively. Methods Due to advances in stem cell-based technologies, we can now model ZIKV infections of the central nervous system in human stem cell-derived neuroprogenitor cells and cerebral organoids, which recapitulate complex three-dimensional neural architecture. We apply Seq-Well—a simple, portable platform for massively parallel single-cell RNA sequencing—to characterize these neural models infected with ZIKV. We detect and quantify host mRNA transcripts and viral RNA with single-cell resolution, thereby defining transcriptional features of both uninfected and infected cells. Results In neuroprogenitor cells, single-cell sequencing reveals that while uninfected bystander cells strongly upregulate interferon pathway genes, these are largely suppressed in cells infected with ZIKV within the same culture dish. In our organoid model, single-cell sequencing allows us to identify multiple cellular populations, including neuroprogenitor cells, intermediate progenitor cells, and terminally differentiated neurons. In this model of the developing brain, we identify preferred tropisms of ZIKV infection. Our data additionally reveal differences in cell-type frequencies and gene expression within organoids infected by historic and contemporary ZIKV strains from a variety of geographic locations. Conclusions These findings may help explain phenotypic differences attributed to the viruses, including variable propensities to cause microcephaly. Overall, our work provides insight into normal and diseased human brain development and suggests that both virus replication and host response mechanisms underlie the neuropathology of ZIKV infection.

scholarly journals Intratumoral molecular genetic heterogeneity of glioblastomas

2020 ◽  
Vol 9 (4) ◽  
pp. 5-11
Author(s):  
P.V. Nikitin ◽  
◽  
M.V. Ryzhova ◽  
A.A. Potapov ◽  
S.A. Galstyan ◽  
...  
Keyword(s):  
Single Cell ◽  
Genetic Heterogeneity ◽  
Tumor Therapy ◽  
Molecular Genetic ◽  
Experimental Treatment ◽  
Intratumoral Heterogeneity ◽  
Cell Populations ◽  
Malignant Neoplasms ◽  
Single Cell Sequencing

Intratumoral molecular genetic heterogeneity is not a less significant challenge in modern oncology than the intertumoral. The presence of cell populations within the same tumor, differing in their molecular properties, translated into phenotypic features of the cells, is one of the reasons for the inefficiency of many developments in the field of tumor therapy and the basis for the progression of malignant neoplasms. The issue under consideration is very relevant for glioblastoma (GBM) – being one of the deadliest human tumors; it practically does not lend itself to even promising experimental treatment methods. Therefore, this paper reviews intratumoral heterogeneity. The review in this aspect examines new experimental data, including those obtained using single-cell technologies, in particular, the key cell populations that make up the pool of tumor cells in glioblastoma, and their molecular metamodules, the presumptive role of some cell populations and their subpopulations in providing tumor malignancy properties. A promising groundwork for fundamentally new approaches to creating personalized diagnostic and therapeutic methods is indicated. Keywords: glioblastoma, intratumoral heterogeneity, glioblastoma genetics, single-cell sequencing

scholarly journals Somatic mutations of activated signaling genes, transcription factors, or tumor suppressors are a precondition for leukemic transformation from myelodysplastic syndromes: a sequencing analysis of 64 paired samples

2021 ◽  
Author(s):  
Xiao Li ◽  
Chun-Kang Chang ◽  
Feng Xu ◽  
Ling-Yun Wu ◽  
Juan Guo ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Single Cell ◽  
Myelodysplastic Syndromes ◽  
Tumor Suppressors ◽  
Somatic Mutations ◽  
Sequencing Analysis ◽  
Single Cell Sequencing ◽  
Paired Samples ◽  
Therapy Targets ◽  
Whole Exome

The transformation biology of secondary AML from MDS is still not fully understood. Here, we performed a large cohort of paired sequences including target, whole-exome and single cell sequencing to search AML transformation- related mutations (TRM). The results showed that fifty-five out of the 64 (85.9%) patients presented presumptive TRM involving activated signaling, transcription factors, or tumor suppressors. Most of TRM (63.6%, 35 cases) emerged at the leukemia transformation point. All five of the remaining nine patients analyzed by paired whole exome sequencing showed TRM which are not included in the reference targets. Single-cell sequencing indicated that the activated cell signaling route was related to TRM which take place prior to phenotypic development. Of note, defined TRM was limited to a small set of genes (less than ten, in the order: NRAS/KRAS, CEBPA, TP53, FLT3, RUNX1, CBL, PTPN11 and WT1, accounted for 91.0% of the mutations). In conclusion, somatic mutations involving in activated signaling, transcription factors, or tumor suppressors appeared to be a precondition for AML transformation from myelodysplastic syndromes. The TRM may be considered as new therapy targets.

scholarly journals Single cell immune profiling reveals a developmentally distinct CD4+ GM-CSF+ T cell lineage that induces GI tract GVHD

2022 ◽  
Author(s):  
Clint Piper ◽  
Emma Hainstock ◽  
Cheng Yin-Yuan ◽  
Yao Chen ◽  
Achia Khatun ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Cell Population ◽  
Cell Populations ◽  
Sequencing Analysis ◽  
Gi Tract ◽  
Gm Csf ◽  
Mediators Of Inflammation ◽  
Ifn Γ

Gastrointestinal (GI) tract involvement is a major determinant for subsequent morbidity and mortality arising during graft versus host disease (GVHD). CD4+ T cells that produce GM-CSF have emerged as central mediators of inflammation in this tissue site as GM-CSF serves as a critical cytokine link between the adaptive and innate arms of the immune system. However, cellular heterogeneity within the CD4+ GM-CSF+ T cell population due to the concurrent production of other inflammatory cytokines has raised questions as to whether these cells have a common ontology or if there exists a unique CD4+ GM-CSF+ subset that differs from other defined T helper (TH) subtypes. Using single cell RNA sequencing analysis, we identified two CD4+ GM-CSF+ T cell populations that arose during GVHD and were distinguishable by the presence or absence of IFN-γ co-expression. CD4+ GM-CSF+ IFN-γ- T cells which emerged preferentially in the colon had a distinct transcriptional profile, employed unique gene regulatory networks, and possessed a non-overlapping TCR repertoire when compared to CD4+ GM-CSF+ IFN-γ+ T cells as well as all other transcriptionally defined CD4+ T cell populations in the colon. Functionally, this CD4+ GM-CSF+ T cell population contributed to pathological damage in the GI tract which was critically dependent upon signaling through the IL-7 receptor but was independent of type 1 interferon signaling. Thus, these studies help to unravel heterogeneity within CD4+ GM-CSF+ T cells that arise during GVHD and define a developmentally distinct colitogenic TH GM-CSF+ subset that mediates immunopathology.

scholarly journals Single Cell Sequencing Analysis Identifies Genetics-Modulated ORMDL3+ Cholangiocytes Having Higher Metabolic Effects On Primary Biliary Cholangitis

2021 ◽  
Author(s):  
Bingyu Xiang ◽  
Chunyu Deng ◽  
Fei Qiu ◽  
Jingjing Li ◽  
Shanshan Li ◽  
...  
Keyword(s):  
Single Cell ◽  
Association Studies ◽  
Liver Cells ◽  
Metabolic Effects ◽  
Primary Biliary Cholangitis ◽  
Genome Wide Association Studies ◽  
Sequencing Analysis ◽  
Summary Statistics ◽  
Genetic Determinants ◽  
Single Cell Sequencing

Abstract Background: Primary biliary cholangitis (PBC) is a classical autoimmune disease, which is highly influenced by genetic determinants. Many genome-wide association studies (GWAS) have reported that numerous genetic loci were significantly associated with PBC susceptibility. However, the effects of genetic determinants on liver cells and its immune microenvironment for PBC remain unclear. Results: We constructed a powerful computational framework to integrate GWAS summary statistics with scRNA-seq data to uncover genetics-modulated liver cell subpopulations for PBC. Based on our multi-omics integrative analysis, 29 risk genes including ORMDL3, GSNK2B, and DDAH2 were significantly associated with PBC susceptibility. By combining GWAS summary statistics with scRNA-seq data, we found that cholangiocytes exhibited a notable enrichment by PBC-related genetic association signals (Permuted P < 0.05). The risk gene of ORMDL3 showed the highest expression proportion in cholangiocytes than other liver cells (22.38%). The ORMDL3+ cholangiocytes have prominently higher metabolism activity score than ORMDL3- cholangiocytes (P = 1.383×10-15). Compared with ORMDL3- cholangiocytes, there were 77 significantly differentially expressed genes among ORMDL3+ cholangiocytes (FDR < 0.05), and these significant genes were associated with autoimmune diseases-related functional terms or pathways. The ORMDL3+ cholangiocytes exhibited relatively high communications with macrophage and monocyte. Compared with ORMDL3- cholangiocytes, the VEGF signaling pathway is specific for ORMDL3+ cholangiocytes to interact with other cell populations. Conclusions: To the best of our knowledge, this is the first study to integrate genetic information with single cell sequencing data for parsing genetics-influenced liver cells for PBC risk. We identified that ORMDL3+ cholangiocytes with higher metabolism activity play important immune-modulatory roles in the etiology of PBC.

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