scholarly journals Recent Advances in Understandings Towards Pathogenesis and Treatment for Intrauterine Adhesion and Disruptive Insights from Single-Cell Analysis

2020 ◽  
Author(s):  
Ross Ka-Kit Leung ◽  
Yixin Lin ◽  
Yanhui Liu
Keyword(s):  
Endothelial Cells ◽  
Stem Cell ◽  
Single Cell ◽  
Expression Profile ◽  
Cell Interaction ◽  
Endometrial Tissue ◽  
Cell Heterogeneity ◽  
Mesenchymal Transition ◽  
Intrauterine Adhesion ◽  
Cell Cell

Abstract Intrauterine adhesion is a major cause of menstrual irregularities, infertility, and recurrent pregnancy losses and the progress towards its amelioration and therapy is slow and unsatisfactory. We aim to summarize and evaluate the current treatment progress and research methods for intrauterine adhesion. We conducted literature review in January 2020 by searching articles at PubMed on prevention and treatment, pathogenesis, the repair of other tissues/organs, cell plasticity, and the stem cell–related therapies for intrauterine adhesion. A total of 110 articles were selected for review. Uterine cell heterogeneity, expression profile, and cell-cell interaction were investigated based on scRNA-seq of uterus provided by Human Cell Landscape (HCL) project. Previous knowledge on intrauterine adhesion (IUA) pathogenesis was mostly derived from correlation studies by differentially expressed genes between endometrial tissue of intrauterine adhesion patients/animal models and normal endometrial tissue. Although the TGF-β1/SMAD pathway was suggested as the key driver for IUA pathogenesis, uterine cell heterogeneity and distinct expression profile among different cell types highlighted the importance of single-cell investigations. Cell-cell interaction in the uterus revealed the central hub of endothelial cells interacting with other cells, with endothelial cells in endothelial to mesenchymal transition and fibroblasts as the strongest interaction partners. The potential of stem cell–related therapies appeared promising, yet suffers from largely animal studies and nonstandard study design. The need to dissect the roles of endometrial cells, endothelial cells, and fibroblasts and their interaction is evident in order to elucidate the molecular and cellular mechanisms in both intrauterine adhesion pathogenesis and treatment.

scholarly journals Single-Cell RNA-Seq Analysis Reveals the Acquisition of Cancer Stem Cell Traits and Increase of Cell–Cell Signaling during EMT Progression

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5726
Author(s):  
Federico Bocci ◽  
Peijie Zhou ◽  
Qing Nie
Keyword(s):  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cell Signaling ◽  
Single Cell ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Intermediate Cell ◽  
Rna Seq ◽  
Mesenchymal Transition ◽  
Cell Cell

Intermediate cell states (ICSs) during the epithelial–mesenchymal transition (EMT) are emerging as a driving force of cancer invasion and metastasis. ICSs typically exhibit hybrid epithelial/mesenchymal characteristics as well as cancer stem cell (CSC) traits including proliferation and drug resistance. Here, we analyze several single-cell RNA-seq (scRNA-seq) datasets to investigate the relation between several axes of cancer progression including EMT, CSC traits, and cell–cell signaling. To accomplish this task, we integrate computational methods for clustering and trajectory inference with analysis of EMT gene signatures, CSC markers, and cell–cell signaling pathways, and highlight conserved and specific processes across the datasets. Our analysis reveals that “standard” measures of pluripotency often used in developmental contexts do not necessarily correlate with EMT progression and expression of CSC-related markers. Conversely, an EMT circuit energy that quantifies the co-expression of epithelial and mesenchymal genes consistently increases along EMT trajectories across different cancer types and anatomical locations. Moreover, despite the high context specificity of signal transduction across different cell types, cells undergoing EMT always increased their potential to send and receive signals from other cells.

scholarly journals Single cell sequencing reveals endothelial plasticity with transient mesenchymal activation after myocardial infarction

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lukas S. Tombor ◽  
David John ◽  
Simone F. Glaser ◽  
Guillermo Luxán ◽  
Elvira Forte ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Single Cell ◽  
Rna Sequencing ◽  
Endothelial Cell Migration ◽  
Metabolic Adaptation ◽  
Endothelial Cell Proliferation ◽  
Mesenchymal Transition ◽  
Single Cell Rna Sequencing

AbstractEndothelial cells play a critical role in the adaptation of tissues to injury. Tissue ischemia induced by infarction leads to profound changes in endothelial cell functions and can induce transition to a mesenchymal state. Here we explore the kinetics and individual cellular responses of endothelial cells after myocardial infarction by using single cell RNA sequencing. This study demonstrates a time dependent switch in endothelial cell proliferation and inflammation associated with transient changes in metabolic gene signatures. Trajectory analysis reveals that the majority of endothelial cells 3 to 7 days after myocardial infarction acquire a transient state, characterized by mesenchymal gene expression, which returns to baseline 14 days after injury. Lineage tracing, using the Cdh5-CreERT2;mT/mG mice followed by single cell RNA sequencing, confirms the transient mesenchymal transition and reveals additional hypoxic and inflammatory signatures of endothelial cells during early and late states after injury. These data suggest that endothelial cells undergo a transient mes-enchymal activation concomitant with a metabolic adaptation within the first days after myocardial infarction but do not acquire a long-term mesenchymal fate. This mesenchymal activation may facilitate endothelial cell migration and clonal expansion to regenerate the vascular network.

scholarly journals Adhesion to type I collagen fibrous gels induces E- to N-cadherin switching without other EMT-related phenotypes in lung carcinoma cell A549

2020 ◽  
Author(s):  
Hitomi Fujisaki ◽  
Sugiko Futaki ◽  
Masashi Yamada ◽  
Kiyotoshi Sekiguchi ◽  
Toshihiko Hayashi ◽  
...  
Keyword(s):  
Single Cell ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
A549 Cells ◽  
Type I ◽  
Mesenchymal Transition ◽  
Cell Behaviors ◽  
Tgf Β1 ◽  
Cells Cultured ◽  
Cell Cell

AbstractIn culture system, environmental factors, such as increasing exogenous growth factors and adhesion to type I collagen (Col-I) induce epithelial-to-mesenchymal transition (EMT) in cells. Col-I molecules maintain a non-fibril form under acidic conditions, and they reassemble into fibrils under physiological conditions. Col-I fibrils often assemble to form three-dimensional gels. The gels and non-gel-form of Col-I can be utilized as culture substrates and different gel-forming state often elicit different cell behaviors. However, gel-form dependent effects on cell behaviors, including EMT induction, remain unclear. EMT induction in lung cancer cell line A549 has been reported via adhesion to Col-I but the effects of gel form dependency are unelucidated. This study investigated the changes in EMT-related behaviors in A549 cells cultured on Col-I gels.We examined cell morphology, proliferation, single-cell migration and expression of EMT-related features in A549 cells cultured on gels or non-gel form of Col-I and non-treated dish with or without transforming growth factor (TGF)-β1. On Col-I gels, some cells kept cell–cell contacts and formed clusters, others maintained single-cell form. In cell–cell contact regions, E-cadherin expression was downregulated, whereas that of N-cadherin was upregulated. Vimentin and integrins α2 and β1 expression were not increased. In TGF-β1-treated A549 cells, cadherin switched from E- to N-cadherin. Their morphology changed to a mesenchymal form and cells scattered with no cluster formation. Vimentin, integrins α2 and β1 expression were upregulated. Thus, we concluded that culture on Col-I fibrous gels induced E- to N-cadherin switching without other EMT-related phenotypes in A549 cells.

Volumetric compression develops noise-driven single-cell heterogeneity

2021 ◽  
Vol 118 (51) ◽  
pp. e2110550118
Author(s):  
Xing Zhao ◽  
Jiliang Hu ◽  
Yiwei Li ◽  
Ming Guo
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Single Molecule ◽  
Regulatory Network ◽  
Network Architecture ◽  
Cell Heterogeneity ◽  
Cell Lung Carcinoma ◽  
Homogeneous Population ◽  
Mesenchymal Transition ◽  
Signature Genes

Recent studies have revealed that extensive heterogeneity of biological systems arises through various routes ranging from intracellular chromosome segregation to spatiotemporally varying biochemical stimulations. However, the contribution of physical microenvironments to single-cell heterogeneity remains largely unexplored. Here, we show that a homogeneous population of non–small-cell lung carcinoma develops into heterogeneous subpopulations upon application of a homogeneous physical compression, as shown by single-cell transcriptome profiling. The generated subpopulations stochastically gain the signature genes associated with epithelial–mesenchymal transition (EMT; VIM, CDH1, EPCAM, ZEB1, and ZEB2) and cancer stem cells (MKI67, BIRC5, and KLF4), respectively. Trajectory analysis revealed two bifurcated paths as cells evolving upon the physical compression, along each path the corresponding signature genes (epithelial or mesenchymal) gradually increase. Furthermore, we show that compression increases gene expression noise, which interplays with regulatory network architecture and thus generates differential cell-fate outcomes. The experimental observations of both single-cell sequencing and single-molecule fluorescent in situ hybridization agrees well with our computational modeling of regulatory network in the EMT process. These results demonstrate a paradigm of how mechanical stimulations impact cell-fate determination by altering transcription dynamics; moreover, we show a distinct path that the ecology and evolution of cancer interplay with their physical microenvironments from the view of mechanobiology and systems biology, with insight into the origin of single-cell heterogeneity.

scholarly journals Single-cell molecular analysis defines therapy response and immunophenotype of stem cell subpopulations in CML

Blood ◽  
2017 ◽  
Vol 129 (17) ◽  
pp. 2384-2394 ◽  
Author(s):  
Rebecca Warfvinge ◽  
Linda Geironson ◽  
Mikael N. E. Sommarin ◽  
Stefan Lang ◽  
Christine Karlsson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Single Cell ◽  
Gene Expression Analysis ◽  
Therapy Response ◽  
Cell Heterogeneity ◽  
Key Points ◽  
Cell Gene Expression ◽  
Cell Subpopulations ◽  
Cell Gene

Key Points Single-cell gene expression analysis reveals CML stem cell heterogeneity and changes imposed by TKI therapy. A subpopulation with primitive, quiescent signature and increased survival to therapy can be high-purity captured as CD45RA−cKIT−CD26+.

scholarly journals Snail is required for TGF -induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells

2008 ◽  
Vol 121 (20) ◽  
pp. 3317-3324 ◽  
Author(s):  
T. Kokudo ◽  
Y. Suzuki ◽  
Y. Yoshimatsu ◽  
T. Yamazaki ◽  
T. Watabe ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Mesenchymal Transition ◽  
Endothelial Mesenchymal Transition

scholarly journals Single Cell Analysis of Circulating Endothelial Cells in Allogeneic Hematopoietic Stem Cell Transplant; To Whom Do They Belong: Host or Donor?

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4885-4885
Author(s):  
Camillo Almici ◽  
Francesca Fontana ◽  
Giovanna Piovani ◽  
Piera Balzarini ◽  
Arabella Neva ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Stem Cell ◽  
Single Cell ◽  
Hematopoietic Stem Cell ◽  
Risk Score ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Str Profile

Background. We recently reported that Circulating Endothelial Cell (CEC) count changes represent a promising marker to monitor endothelial damage in patients undergoing allogeneic hematopoietic stem cell transplant (allo-HSCT), potentially becoming a valuable tool in the diagnostic definition of GVHD. Besides confirming an increase of CEC counts at GVHD onset, we repeatedly documented at time of engraftment statistically significant higher numbers of CEC in patients who will not manifest GVHD in comparison to patients in which GVHD will be diagnosed (Transplantation 2014,98:706-12; Bone Marrow Transplantation 2017,52:1637-42; Scientific Reports 2019,9:1-12). Recent knowledges in organ transplant pointed out that endothelial cells from the grafted organ, besides being a continuous source of alloantigens, can downregulate alloreactivity exerting tolerogenic responses. By inference to the allo-HSCT field, it could be envisaged that presence of donor CEC could induce protective effects on alloreactivity. Methods. We planned a study to test the hypothesis that at time of engraftment, CEC present in peripheral blood (PB), besides coming from cells shedding from patient vasculature, could partly belong to donor, originating from the cellular graft. Therefore, in an exploratory set, we performed FISH analysis on flowcytometry-sorted CEC (CD45neg/CD34bright/CD146pos, Lyotube #623920, BD Biosciences) (n=3) and on whole PB derived culture-expanded CEC (n=3) (EGM-2 BulletKit, Lonza), obtained at engraftment in sex-mismatched allo-HSCT. In the confirmatory set (n=15), single CEC were recovered from PB, at engraftment (T1) and at 90 days (T2) after allo-HSCT, through the DEPArrayTM technology (Menarini Silicon Biosystems), after preliminary bulk separation step carried out with the CellSearch® System. Single recovered CEC was whole genome amplified (Ampli1™ WGA Kit) and short tandem repeat (STR) profile determined (Ampli 1TM STR kit) on each single CEC. To confirm host/donor origin, single CEC STR profile was compared to that determined on patient and donor cells before allo-HSCT. Moreover, donor CEC presence was evaluated by CISH analysis on formaline fixed and paraffin-embedded biopsy sections obtained at least three months after sex mismatched allo-HSCT. Results. By positive findings of the exploratory set, we proved, at the single cell level in the confirmatory set, the presence of donor CEC at engraftment (T1) in 4 out of 15 patients (Table 1). Of them, 2 did not manifested GVHD, despite a GVHD risk score of 2, and the other 2 presented GVHD grade I. On the contrary, among the 10 patients in whom no donor CEC were detected, 6 experienced GVHD grade II-III, while 4 did not manifested GVHD, despite a 1-3 GVHD risk score. Conclusions. Our data represent the proof of principle that donor CEC may flow in host PB early on from hematopoietic recovery and seldom persist thereafter at steady-state conditions, being potentially embedded in host vascular wall. These puzzling findings suggest that neovascularization takes place in parallel with hematopoietic engraftment and could provide further clues on shedding light on tissue tolerance in the context of GVHD, opening up paradoxical scenarios on the protective role potentially played by donor CEC. Disclosures Fontana: Menarini Silicon Biosystem: Employment. Rotta:BD Biosciences Italia: Employment. Manaresi:Menarini SIlicon Biosystem: Employment, Membership on an entity's Board of Directors or advisory committees.

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