Self-Organized Critical Control of Genome Expression: Novel Scenario on Cell-Fate Decision

AbstractIn our current studies on whole genome expression in several biological processes, we have demonstrated the actual existence of self-organized critical control (SOC) of gene expression at both population and single cell level. SOC allows for cell-fate change by critical transition encompassing the entire genome expression that, in turn, is partitioned into distinct response domains (critical states).In this paper, we go more in depth into the elucidation of SOC control of genome expression focusing on the determination of critical point (CP) and associated distinct critical states in single-cell genome expression. This leads us to the proposal of a potential universal model with genome-engine mechanism for cell-fate change. Our findings suggest that the CP is fixed point in terms of temporal expression variance, where the CP (set of critical genes) becomes active (ON) for cell-fate change (‘super-critical’ in genome-state) or else inactive (OFF) state (‘sub-critical’ in genome-state); this may lead to a novel scenario of the cell-fate control through activating or inactivating CP.

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A Unified Genomic Mechanism of Cell-Fate Change

10.1101/2021.11.24.469848 ◽

2021 ◽

Author(s):

Masa Tsuchiya ◽

Alessandro Giuliani ◽

Giovanna Zimatore ◽

Jekaterina Erenpreisa ◽

Kenichi Yoshikawa

Keyword(s):

Cell Fate ◽

Hot Spots ◽

Center Of Mass ◽

Local Perturbation ◽

Whole Genome ◽

Entire Genome ◽

Collective Behaviors ◽

Genome Expression ◽

Temporal Variance ◽

Whole Genome Expression

The purpose of our studies is to elucidate the nature of massive control of whole genome expression with a particular emphasis on cell-fate change. Whole genome expression is coordinated by the emergence of a critical point (CP: a peculiar set of bi-phasic genes) through the genome-engine. In response to stimuli, the genome expression self-organizes three critical states, each exhibiting distinct collective behaviors with its center of mass acting as a local attractor, coexisting with whole genome attractor (GA). Genome-engine mechanism accounts for local attractors interaction in phase space. The CP acts as the organizing center of cell-fate change, and its activation makes local perturbation spread over the genome affecting GA. The activation of CP is in turn elicited by hot-spots genes with elevated temporal variance, normally in charge to keep genome expression at pace with microenvironment fluctuations. When hot-spots oscillation exceeds a given threshold, the CP synchronizes with the GA driving genome expression state transition. The expression synchronization wave invading the entire genome depends on the power law fusion-bursting dynamics of silencing pericentromere-associated heterochromatin domains and the consequent folding-unfolding status of transcribing euchromatin domains. The proposed mechanism is a unified step toward a time-evolutional transition theory of biological regulation.

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Self-Organization of Whole Gene Expression through Coordinated Chromatin Structural Transition: Validation of Self-Organized Critical Control of Genome Expression

10.1101/852681 ◽

2019 ◽

Cited By ~ 2

Author(s):

Giovanna Zimatore ◽

Masa Tsuchiya ◽

Midori Hashimoto ◽

Andrzej Kasperski ◽

Alessandro Giuliani

Keyword(s):

Gene Expression ◽

Cell Fate ◽

Principal Component ◽

Self Organization ◽

Specific Gene ◽

List Type ◽

Entire Genome ◽

Self Organized ◽

Critical Transitions ◽

Genome Expression

AbstractThrough our studies on whole genome regulation, we have demonstrated the existence of self-organized critical control (SOC) of whole gene expression - genomic self-organization mechanism through the emergence of a critical point (CP) at both the cell population and single cell level. In this paper, based on HRG and EGF-stimulated MCF-7 breast-cancer cell line, we shed light on the origin of critical transitions stemming from coordinated chromatin remodeling. In so doing, we validated the core of the SOC control mechanism through the application of a non-linear signal analysis technique (Recurrence Quantification Analysis: RQA), and of Principal Component Analysis (PCA). The main findings were: Transcriptional co-regulation follows a strong and invariant exponential decay as between gene spacing along the chromosome is increased. This shows that the co-regulation occurs on a mainly positional basis reflecting local chromatin organization.There are two main fluctuation modes on the top of the cell-kind specific gene expression values spanning the entire genome expression. These modes establish an autonomous genomic critical control system (genome-engine) through the activation of the CP for cell-fate guiding critical transitions revealed by SOC analysis.The elucidation of the link between spatial position on chromosome and co-regulation together with the identification of specific locations on the genome devoted to the generalization of perturbation stimuli, give a molecular basis to the self-organization dynamics of genome expression and cell-fate decision.

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Single-cell genome expression analysis?

Trends in Biotechnology ◽

10.1016/s0167-7799(02)02068-1 ◽

2002 ◽

Vol 20 (11) ◽

pp. 449

Author(s):

Daniel Figeys

Keyword(s):

Single Cell ◽

Expression Analysis ◽

Genome Expression ◽

Cell Genome ◽

Single Cell Genome

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Integrated time-lapse and single-cell transcription studies highlight the variable and dynamic nature of human hematopoietic cell fate commitment

10.1101/101428 ◽

2017 ◽

Cited By ~ 1

Author(s):

Alice Moussy ◽

Jérémie Cosette ◽

Romuald Parmentier ◽

Cindy da Silva ◽

Guillaume Corre ◽

...

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Single Cell ◽

Cell Fate ◽

Morphological Changes ◽

Gene Expression Pattern ◽

Time Lapse ◽

Dynamic Nature ◽

Transcriptional Changes ◽

Fate Decision

AbstractIndividual cells take lineage commitment decisions in a way that is not necessarily uniform. We address this issue by characterizing transcriptional changes in cord blood derived CD34+ cells at the single-cell level and integrating data with cell division history and morphological changes determined by time-lapse microscopy. We show, that major transcriptional changes leading to a multilineage-primed gene expression state occur very rapidly during the first cell cycle. One of the two stable lineage-primed patterns emerges gradually in each cell with variable timing. Some cells reach a stable morphology and molecular phenotype by the end of the first cell cycle and transmit it clonally. Others fluctuate between the two phenotypes over several cell cycles. Our analysis highlights the dynamic nature and variable timing of cell fate commitment in hematopoietic cells, links the gene expression pattern to cell morphology and identifies a new category of cells with fluctuating phenotypic characteristics, demonstrating the complexity of the fate decision process, away from a simple binary switch between two options as it is usually envisioned.

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

Nature Metabolism ◽

10.1038/s42255-020-00318-y ◽

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

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Single cell response landscape of graded Nodal signaling in zebrafish explants

10.1101/2021.04.25.441305 ◽

2021 ◽

Author(s):

Tao Cheng ◽

Yanyi Xing ◽

Yunfei Li ◽

Cong Liu ◽

Ying Huang ◽

...

Keyword(s):

Single Cell ◽

Cell Fate ◽

Cell Response ◽

Expression Patterns ◽

Cell Types ◽

Nodal Signaling ◽

Animal Pole ◽

Fate Decision ◽

Single Cell Response

Nodal, as a morphogen, plays important roles in cell fate decision, pattern formation and organizer function. But because of the complex context in vivo and technology limitations, systematic studying of genes, cell types and patterns induced by Nodal alone is still missing. Here, by using a relatively simplified model, the zebrafish blastula animal pole explant avoiding additional instructive signals and prepatterns, we constructed a single cell response landscape of graded Nodal signaling, identified 105 Nodal immediate targets and depicted their expression patterns. Our results show that Nodal signaling is sufficient to induce anterior-posterior patterned axial mesoderm and head structure. Surprisingly, the endoderm induced by Nodal alone is mainly the anterior endoderm which gives rise to the pharyngeal pouch only, but not internal organs. Among the 105 Nodal targets, we identified 14 genes carrying varying levels of axis induction capability. Overall, our work provides new insights for understanding of the Nodal function and a valuable resource for future studies of patterning and morphogenesis induced by it.

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Cell-fate decision of mesenchymal stem cells toward osteocyte differentiation is committed by cell condensed condition in spheroid culture

10.1101/2020.12.09.417097 ◽

2020 ◽

Author(s):

Jeonghyun Kim ◽

Taiji Adachi

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cell Fate ◽

Actin Polymerization ◽

Cell Fate Decision ◽

Spheroid Culture ◽

Self Organized ◽

Culture Model ◽

Fate Decision

AbstractOsteocytes are mechanosensory commander cells to regulate bone remodeling throughout the lifespan. While the osteocyte is known as a terminally differentiated cell derived from mesenchymal stem cell, the detailed mechanisms of cell-fate decision toward osteocyte differentiation still remain unclear. In this study, we fabricated three-dimensional (3D) self-organized spheroids using human mesenchymal stem cells (hMSCs). Under the osteogenesis induction medium, the spheroid culture model exerted the osteocyte-likeness within 2 days compared to a conventional 2D monolayer model. By using an inhibitor of actin polymerization, we showed an involvement of actin balancing in the osteocyte differentiation in the spheroid. Notably, we represented that the cell condensed condition acquired in the 3D spheroid culture model determined a differentiation fate of MSCs to osteocytes via actin balancing. Taken together, we suggest that our self-organized spheroid model can be utilized as a new in vitro model to represent the osteocyte differentiation process and further to recapitulate an in vitro ossification process.

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Decision tree models and cell fate choice

10.1101/2020.12.19.423629 ◽

2020 ◽

Author(s):

Ivan Croydon Veleslavov ◽

Michael P.H. Stumpf

Keyword(s):

Gene Expression ◽

Single Cell ◽

Cell Fate ◽

Cell Types ◽

Lineage Tree ◽

Tree Models ◽

Fate Decision ◽

Average Gene ◽

Lineage Trees ◽

Cell Data

AbstractSingle cell transcriptomics has laid bare the heterogeneity of apparently identical cells at the level of gene expression. For many cell-types we now know that there is variability in the abundance of many transcripts, and that average transcript abun-dance or average gene expression can be a unhelpful concept. A range of clustering and other classification methods have been proposed which use the signal in single cell data to classify, that is assign cell types, to cells based on their transcriptomic states. In many cases, however, we would like to have not just a classifier, but also a set of interpretable rules by which this classification occurs. Here we develop and demonstrate the interpretive power of one such approach, which sets out to establish a biologically interpretable classification scheme. In particular we are interested in capturing the chain of regulatory events that drive cell-fate decision making across a lineage tree or lineage sequence. We find that suitably defined decision trees can help to resolve gene regulatory programs involved in shaping lineage trees. Our approach combines predictive power with interpretabilty and can extract logical rules from single cell data.

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

10.1101/476127 ◽

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.

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