Exploring the role of autophagy during early human embryonic development through single-cell transcriptome and methylome analyses

2021 ◽  
Author(s):  
Shi Song ◽  
Qianying Guo ◽  
Yiru Zhu ◽  
Peng Yuan ◽  
Zhiqiang Yan ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Single Cell ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome ◽  
Early Human

scholarly journals Landscape Of M6a RNA Methylation Regulators and Tumor Microenvironment Cell-Infiltration Characterization In Gastroesophageal Adenocarcinomas

2021 ◽  
Author(s):  
Duanrui Liu ◽  
Jingyu Zhu ◽  
Zongming Wang ◽  
Yusong Fang ◽  
Mingjie Yuan ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Rna Methylation ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Abstract Background: RNA N6-methyladenosine (m6A) modification plays a nonnegligible role in shaping individual tumor microenvironment (TME) characterizations. However, the landscape and relationship of m6A modification and TME cell infiltration remain unknown in gastroesophageal adenocarcinomas (GEA). Methods: We systematically examined the TME of GEA focusing on the distinct m6A modification patterns from the public databases. Intrinsic patterns of m6A modification were evaluated for associations with clinicopathological characteristics, underlying biological pathways, tumor immune cell infiltration, oncological outcomes and treatment responses. We generated a single-cell transcriptome atlas of the GEA sample inhouse to validate the role of the m6A modification pattern on TME.Results: We identified and validated the landscape of m6A regulators and tumor-infiltrating immune cells in GEA. Then, two distinct m6A modification patterns of GEA (cluster1/2 subgroup) were defined, and we correlated two subgroups with TME cell-infiltrating characteristics. Cluster2 subgroup correlates with a poorer prognosis, down-regulated PD-1 expression, higher risk scores and distinct immune cell infiltration. Additionally, PPI and WGCNA network analysis were integrated to identify key module genes closely related to immune infiltration of GEA to find immunotherapy markers. And COL4A1 and COL5A2 in brown module were significantly correlated to the prognosis, PD-1/L1 and CTLA-4 expression of GEA patients. Interesting, low COL5A2 expression was linked to an enhanced response to anti-PD-1 immunotherapy. Finally, a prognostic risk score was constructed using three m6A regulator-associated signatures that represented an independent prognosis factor for GEA. The single-cell transcriptome atlas of GEA sample validated the role of m6A modification pattern on TME and revealed that three m6A regulators are highly expressed in CD4+ T cells, CD8+ T cells, Tregs and Macrophages.Conclusions: Our work revealed m6A RNA methylation regulators are a type of vital participant in the malignant progression and TME diversity of GEA. m6A modification patterns of COL5A2 may be the potential biomarker contributes to predicting the response to anti-PD-1 immunotherapy.

scholarly journals Single cell transcriptome atlas of mouse mammary epithelial cells across development

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Bhupinder Pal ◽  
Yunshun Chen ◽  
Michael J. G. Milevskiy ◽  
François Vaillant ◽  
Lexie Prokopuk ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Single Cell ◽  
Developmental Stages ◽  
Mammary Epithelial Cells ◽  
Expression Profiles ◽  
Single Cells ◽  
Chromatin Accessibility ◽  
Mammary Epithelial ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Abstract Background Heterogeneity within the mouse mammary epithelium and potential lineage relationships have been recently explored by single-cell RNA profiling. To further understand how cellular diversity changes during mammary ontogeny, we profiled single cells from nine different developmental stages spanning late embryogenesis, early postnatal, prepuberty, adult, mid-pregnancy, late-pregnancy, and post-involution, as well as the transcriptomes of micro-dissected terminal end buds (TEBs) and subtending ducts during puberty. Methods The single cell transcriptomes of 132,599 mammary epithelial cells from 9 different developmental stages were determined on the 10x Genomics Chromium platform, and integrative analyses were performed to compare specific time points. Results The mammary rudiment at E18.5 closely aligned with the basal lineage, while prepubertal epithelial cells exhibited lineage segregation but to a less differentiated state than their adult counterparts. Comparison of micro-dissected TEBs versus ducts showed that luminal cells within TEBs harbored intermediate expression profiles. Ductal basal cells exhibited increased chromatin accessibility of luminal genes compared to their TEB counterparts suggesting that lineage-specific chromatin is established within the subtending ducts during puberty. An integrative analysis of five stages spanning the pregnancy cycle revealed distinct stage-specific profiles and the presence of cycling basal, mixed-lineage, and 'late' alveolar intermediates in pregnancy. Moreover, a number of intermediates were uncovered along the basal-luminal progenitor cell axis, suggesting a continuum of alveolar-restricted progenitor states. Conclusions This extended single cell transcriptome atlas of mouse mammary epithelial cells provides the most complete coverage for mammary epithelial cells during morphogenesis to date. Together with chromatin accessibility analysis of TEB structures, it represents a valuable framework for understanding developmental decisions within the mouse mammary gland.

Sign in / Sign up

Export Citation Format

Share Document