scholarly journals Defining multistep cell fate decision pathways during pancreatic development at single‐cell resolution

2019 ◽  
Vol 38 (8) ◽  
Author(s):  
Xin‐Xin Yu ◽  
Wei‐Lin Qiu ◽  
Liu Yang ◽  
Yu Zhang ◽  
Mao‐Yang He ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Cell Fate Decision ◽  
Pancreatic Development ◽  
Fate Decision

Stepwise cell fate decision pathways during osteoclastogenesis at single-cell resolution

2020 ◽  
Vol 2 (12) ◽  
pp. 1382-1390
Author(s):  
Masayuki Tsukasaki ◽  
Nam Cong-Nhat Huynh ◽  
Kazuo Okamoto ◽  
Ryunosuke Muro ◽  
Asuka Terashima ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Cell Fate Decision ◽  
Fate Decision

scholarly journals Newly developed single-cell computational approach elucidates the stabilization of Oct4 expression in the E3.25 mouse preimplantation embryo

2018 ◽  
Author(s):  
Daniela Gerovska ◽  
Marcos J. Arauzo-Bravo
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Clustering Algorithm ◽  
Preimplantation Embryo ◽  
Outer Cell ◽  
Cell Fate Decision ◽  
Oct4 Expression ◽  
Mouse Preimplantation Embryo ◽  
Fate Decision ◽  
Canonical Wnt

AbstractThe time of onset of the second cell fate decision in the mouse preimplantation embryo is still unknown. Ohnishi et al. (2014) looked for cell heterogeneity in the ICM at E3.25 that could indicate the time preceding the apparent segregation of PE and EPI at E3.5, but were not able to detect an early splitting transcriptomics event using state-of-the-art clustering techniques. We developed a new clustering algorithm, hierarchical optimal k-means (HOkM), and identified from single cell (sc) transcriptomics microarray data two groups of ICM cells during the 32 to 64 mouse embryo transition: from embryos with less than 34 cells, and more than 33 cells, corresponding to two developmental sub-stages. The genes defining these sub-stages indicate that the development of the embryo to 34 cells triggers a dramatic event as a result of which Bsg is high expressed, the canonical Wnt pathway is activated, Oct4 is stabilized to high expression and the chromatin remodeling program is initialized to establish a very early narve pluripotent state from the preceding totipotency. We characterized our HOkM partition comparing with independent scRNA-seq datasets. It was staggering to discover that from the 3.4360×1010 possible bi-partitions of the E3.25 data of Ohnishi et al. (2014), our HOkM discovered one partition that shares the biological features of the early and late 32 ICM cells of Posfai et al. (2017). We propose that the stabilization of Oct4 expression is a non-cell autonomous process that requires a minimal number of four inner cell contacts acquired during the transition from a homogeneous outer-cell environment to a heterogeneous inner/outer cell environment formed by the niche of a kernel of at least six inner cells covered by trophectoderm.

scholarly journals Developmental switching inPhysarum polycephalum: Petri net analysis of single cell trajectories of gene expression indicates responsiveness and genetic plasticity of the Waddington quasipotential landscape

2017 ◽  
Author(s):  
Britta Werthmann ◽  
Wolfgang Marwan
Keyword(s):  
Gene Expression ◽  
Petri Nets ◽  
Single Cell ◽  
Cell Fate ◽  
Petri Net ◽  
Single Cells ◽  
Cell Fate Decision ◽  
Stimulus Pulse ◽  
Fate Decision ◽  
Cell Trajectories

AbstractThe developmental switch to sporulation inPhysarum polycephalumis a phytochrome-mediated far-red light-induced cell fate decision that synchronously encompasses the entire multinucleate plasmodial cell and is associated with extensive reprogramming of the transcriptome. By repeatedly taking samples of single cells after delivery of a light stimulus pulse, we analysed differential gene expression in two mutant strains and in a heterokaryon of the two strains all of which display a different propensity for making the cell fate decision. Multidimensional scaling of the gene expression data revealed individually different single cell trajectories eventually leading to sporulation. Characterization of the trajectories as walks through states of gene expression discretized by hierarchical clustering allowed the reconstruction of Petri nets that model and predict the observed behavior. Structural analyses of the Petri nets indicated stimulus- and genotype-dependence of both, single cell trajectories and of the quasipotential landscape through which these trajectories are taken. The Petri net-based approach to the analysis and decomposition of complex cellular responses and of complex mutant phenotypes may provide a scaffold for the data-driven reconstruction of causal molecular mechanisms that shape the topology of the quasipotential landscape.

scholarly journals Investigating higher order interactions in single cell data with scHOT

2019 ◽  
Author(s):  
Shila Ghazanfar ◽  
Yingxin Lin ◽  
Xianbin Su ◽  
David M. Lin ◽  
Ellis Patrick ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Expression Profiles ◽  
Order Effect ◽  
Higher Order ◽  
Cell Fate Decision ◽  
Cell Fate Decisions ◽  
Novel Approach ◽  
Fate Decision ◽  
Cell Data

ABSTRACTSingle-cell RNA-sequencing has transformed our ability to examine cell fate choice. For example, in the context of development and differentiation, computational ordering of cells along ‘pseudotime’ enables the expression profiles of individual genes, including key transcription factors, to be examined at fine scale temporal resolution. However, while cell fate decisions are typically marked by profound changes in expression, many such changes are observed in genes downstream of the initial cell fate decision. By contrast, the genes directly involved in the cell fate decision process are likely to interact in subtle ways, potentially resulting in observed changes in patterns of correlation and variation rather than mean expression prior to cell fate commitment. Herein, we describe a novel approach, scHOT – single cell Higher Order Testing - which provides a flexible and statistically robust framework for identifying changes in higher order interactions among genes. scHOT is general and modular in nature, can be run in multiple data contexts such as along a continuous trajectory, between discrete groups, and over spatial orientations; as well as accommodate any higher order measurement such as variability or correlation. We demonstrate the utility of scHOT by studying embryonic development of the liver, where we find coordinated changes in higher order interactions of programs related to differentiation and liver function. We also demonstrate its ability to find subtle changes in gene-gene correlation patterns across space using spatially-resolved expression data from the mouse olfactory bulb. scHOT meaningfully adds to first order effect testing, such as differential expression, and provides a framework for interrogating higher order interactions from single cell data.

scholarly journals Deciphering Cell Fate Decision by Integrated Single-Cell Sequencing Analysis

2020 ◽  
Vol 3 (1) ◽  
pp. 1-22 ◽  
Author(s):  
Sagar ◽  
Dominic Grün
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Cell Biology ◽  
Cellular Differentiation ◽  
Sequencing Analysis ◽  
Cell Fate Decision ◽  
Modern Biology ◽  
Health And Disease ◽  
Fate Decision ◽  
Multicellular Organisms

Cellular differentiation is a common underlying feature of all multicellular organisms through which naïve cells progressively become fate restricted and develop into mature cells with specialized functions. A comprehensive understanding of the regulatory mechanisms of cell fate choices during development, regeneration, homeostasis, and disease is a central goal of modern biology. Ongoing rapid advances in single-cell biology are enabling the exploration of cell fate specification at unprecedented resolution. Here, we review single-cell RNA sequencing and sequencing of other modalities as methods to elucidate the molecular underpinnings of lineage specification. We specifically discuss how the computational tools available to reconstruct lineage trajectories, quantify cell fate bias, and perform dimensionality reduction for data visualization are providing new mechanistic insights into the process of cell fate decision. Studying cellular differentiation using single-cell genomic tools is paving the way for a detailed understanding of cellular behavior in health and disease.

scholarly journals Cell fate clusters in ICM organoids arise from cell fate heredity and division: a modelling approach

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tim Liebisch ◽  
Armin Drusko ◽  
Biena Mathew ◽  
Ernst H. K. Stelzer ◽  
Sabine C. Fischer ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Division ◽  
Cell Fate ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Cell Lineage ◽  
Cell Fate Decision ◽  
Cell Fate Decisions ◽  
Chemical Signalling ◽  
Fate Decision

AbstractDuring the mammalian preimplantation phase, cells undergo two subsequent cell fate decisions. During the first decision, the trophectoderm and the inner cell mass are formed. Subsequently, the inner cell mass segregates into the epiblast and the primitive endoderm. Inner cell mass organoids represent an experimental model system, mimicking the second cell fate decision. It has been shown that cells of the same fate tend to cluster stronger than expected for random cell fate decisions. Three major processes are hypothesised to contribute to the cell fate arrangements: (1) chemical signalling; (2) cell sorting; and (3) cell proliferation. In order to quantify the influence of cell proliferation on the observed cell lineage type clustering, we developed an agent-based model accounting for mechanical cell–cell interaction, i.e. adhesion and repulsion, cell division, stochastic cell fate decision and cell fate heredity. The model supports the hypothesis that initial cell fate acquisition is a stochastically driven process, taking place in the early development of inner cell mass organoids. Further, we show that the observed neighbourhood structures can emerge solely due to cell fate heredity during cell division.

scholarly journals Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: the regulation and intervention

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xudong Zhu ◽  
Zhiyang Chen ◽  
Weiyan Shen ◽  
Gang Huang ◽  
John M. Sedivy ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cellular Response ◽  
State Of The Art ◽  
Cell Senescence ◽  
Therapeutic Interventions ◽  
Cell Fate Decision ◽  
The Past ◽  
Fate Decision ◽  
The Individual ◽  
Remarkable Progress

AbstractRemarkable progress in ageing research has been achieved over the past decades. General perceptions and experimental evidence pinpoint that the decline of physical function often initiates by cell senescence and organ ageing. Epigenetic dynamics and immunometabolic reprogramming link to the alterations of cellular response to intrinsic and extrinsic stimuli, representing current hotspots as they not only (re-)shape the individual cell identity, but also involve in cell fate decision. This review focuses on the present findings and emerging concepts in epigenetic, inflammatory, and metabolic regulations and the consequences of the ageing process. Potential therapeutic interventions targeting cell senescence and regulatory mechanisms, using state-of-the-art techniques are also discussed.

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