MicroRNA: basic mechanisms and transcriptional regulatory networks for cell fate determination

1.AbstractThe emergence of multicellular organisms that exhibit cell differentiation and stereotypic spatial arrangements has been recognized as one of the major transitions in evolution. Myxobacteria have emerged as a useful study model to investigate multicellular evolution and development. Here, we propose a multiscale model that considers cellular adhesion and movement, molecular regulatory networks (MRNs), and cell-to-cell communication to study the emergence of cell fate determination and spatial patterning of Myxococcus xanthus fruiting bodies. The model provides a dynamic accounting of the roles of MRN multistability, intercellular communication and conglomerate size in determining cell fate and patterning during M. xanthus development. It also suggests that for cell fate determination and patterning to occur, the cell aggregate must surpass a minimum size. The model also allows us to contrast alternative scenarios for the C-signal mechanism and provides stronger support for an indirect effect (as a diffusible molecule) than a direct one (as a membrane protein).

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ComplexGRN complex GeneComplex GRN Regulatory Networks – from Structure to Biological Observables: Cell Fate DeterminationGene regulation, cell fate determination

Encyclopedia of Complexity and Systems Science ◽

10.1007/978-0-387-30440-3_79 ◽

2009 ◽

pp. 1180-1213 ◽

Cited By ~ 18

Author(s):

Sui Huang ◽

Stuart A. Kauffman

Keyword(s):

Cell Fate ◽

Regulatory Networks ◽

Cell Fate Determination ◽

Fate Determination

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ComplexGRN complex GeneComplex GRN Regulatory Networks – from Structure to Biological Observables: Cell Fate DeterminationGene regulation, cell fate determination

Computational Complexity ◽

10.1007/978-1-4614-1800-9_35 ◽

2012 ◽

pp. 527-560 ◽

Cited By ~ 6

Author(s):

Sui Huang ◽

Stuart A. Kauffman

Keyword(s):

Cell Fate ◽

Regulatory Networks ◽

Cell Fate Determination ◽

Fate Determination

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osr1 couples intermediate mesoderm cell fate with temporal dynamics of vessel progenitor cell differentiation

Development ◽

10.1242/dev.198408 ◽

2021 ◽

Author(s):

Elliot A. Perens ◽

Jessyka T. Diaz ◽

Agathe Quesnel ◽

Amjad Askary ◽

J. Gage Crump ◽

...

Keyword(s):

Transcription Factor ◽

Cell Fate ◽

Regulatory Networks ◽

Temporal Dynamics ◽

Bhlh Transcription Factor ◽

Transcriptional Regulatory Networks ◽

Mesoderm Cell ◽

Intermediate Mesoderm ◽

Transcriptional Regulatory ◽

Mutant Phenotypes

Transcriptional regulatory networks refine gene expression boundaries to define the dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that establish the boundary between the IM and neighboring vessel progenitors are poorly understood. Here, we delineate roles for the zinc finger transcription factor Osr1 in kidney and vessel progenitor development. Zebrafish osr1 mutants display decreased IM formation and premature emergence of lateral vessel progenitors (LVPs). These phenotypes contrast with the increased IM and absent LVPs observed with loss of the bHLH transcription factor Hand2, and loss of hand2 partially suppresses osr1 mutant phenotypes. hand2 and osr1 are expressed together in the posterior mesoderm, but osr1 expression decreases dramatically prior to LVP emergence. Overexpressing osr1 during this timeframe inhibits LVP development while enhancing IM formation and can rescue the osr1 mutant phenotype. Together, our data demonstrate that osr1 modulates the extent of IM formation and the temporal dynamics of LVP development, suggesting that a balance between levels of osr1 and hand2 expression is essential to demarcate the kidney and vessel progenitor territories.

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ANANSE: An enhancer network-based computational approach for predicting key transcription factors in cell fate determination

10.1101/2020.06.05.135798 ◽

2020 ◽

Author(s):

Quan Xu ◽

Georgios Georgiou ◽

Gert Jan C. Veenstra ◽

Huiqing Zhou ◽

Simon J. van Heeringen

Keyword(s):

Transcription Factors ◽

Cell Fate ◽

Gene Regulatory Networks ◽

Regulatory Networks ◽

Cell Types ◽

Cell Fate Determination ◽

Cell Type ◽

Fate Determination ◽

Cell Type Specific ◽

Gene Regulatory

AbstractProper cell fate determination is largely orchestrated by complex gene regulatory networks centered around transcription factors. However, experimental elucidation of key transcription factors that drive cellular identity is currently often intractable. Here, we present ANANSE (ANalysis Algorithm for Networks Specified by Enhancers), a network-based method that exploits enhancer-encoded regulatory information to identify the key transcription factors in cell fate determination. As cell type-specific transcription factors predominantly bind to enhancers, we use regulatory networks based on enhancer properties to prioritize transcription factors. First, we predict genome-wide binding profiles of transcription factors in various cell types using enhancer activity and transcription factor binding motifs. Subsequently, applying these inferred binding profiles, we construct cell type-specific gene regulatory networks, and then predict key transcription factors controlling cell fate conversions using differential gene networks between cell types. This method outperforms existing approaches in correctly predicting major transcription factors previously identified to be sufficient for trans-differentiation. Finally, we apply ANANSE to define an atlas of key transcription factors in 18 normal human tissues. In conclusion, we present a ready-to-implement computational tool for efficient prediction of transcription factors in cell fate determination and to study transcription factor-mediated regulatory mechanisms. ANANSE is freely available at https://github.com/vanheeringen-lab/ANANSE.

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Complex Gene Regulatory Networks - from Structure to Biological Observables: Cell Fate Determination

10.1007/springerreference_60251 ◽

2011 ◽

Keyword(s):

Cell Fate ◽

Gene Regulatory Networks ◽

Regulatory Networks ◽

Cell Fate Determination ◽

Fate Determination ◽

Gene Regulatory

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osr1 couples intermediate mesoderm cell fate with temporal dynamics of vessel progenitor cell differentiation

10.1101/2020.11.14.383141 ◽

2020 ◽

Cited By ~ 1

Author(s):

Elliot A. Perens ◽

Jessyka T. Diaz ◽

Agathe Quesnel ◽

Amjad Askary ◽

J. Gage Crump ◽

...

Keyword(s):

Transcription Factor ◽

Cell Fate ◽

Regulatory Networks ◽

Temporal Dynamics ◽

Bhlh Transcription Factor ◽

Transcriptional Regulatory Networks ◽

Mesoderm Cell ◽

Intermediate Mesoderm ◽

Transcriptional Regulatory ◽

Mutant Phenotypes

ABSTRACTTranscriptional regulatory networks refine gene expression boundaries throughout embryonic development to define the precise dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that establish the boundary between the IM and its neighboring vessel progenitors are poorly understood. Here, we delineate new roles for the zinc finger transcription factor Osr1 in kidney and vessel progenitor development. Zebrafish osr1 mutants display decreased IM formation and premature emergence of neighboring lateral vessel progenitors (LVPs). These phenotypes contrast with the increased IM and absent LVPs observed with loss of the bHLH transcription factor Hand2, and loss of hand2 partially suppresses the osr1 mutant phenotypes. hand2 and osr1 are both expressed in the posterior lateral mesoderm, but osr1 expression decreases dramatically prior to LVP emergence. Overexpressing osr1 inhibits LVP development while enhancing IM formation. Together, our data demonstrate that osr1 modulates both the extent of IM formation and the temporal dynamics of LVP development, suggesting that a balance between levels of osr1 and hand2 expression is essential to demarcate the dimensions of kidney and vessel progenitor territories.SUMMARY STATEMENTAnalysis of the osr1 mutant phenotype reveals roles in determining the extent of intermediate mesoderm formation while inhibiting premature differentiation of neighboring vessel progenitors.

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Transient hysteresis and inherent stochasticity in gene regulatory networks

Nature Communications ◽

10.1038/s41467-019-12344-w ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 2

Author(s):

M. Pájaro ◽

I. Otero-Muras ◽

C. Vázquez ◽

A. A. Alonso

Keyword(s):

Cell Fate ◽

Gene Regulatory Networks ◽

Cellular Response ◽

Regulatory Networks ◽

Initial Conditions ◽

Quantitative Description ◽

Hysteresis Phenomenon ◽

Cell Fate Determination ◽

Fate Determination ◽

Gene Regulatory

Abstract Cell fate determination, the process through which cells commit to differentiated states is commonly mediated by gene regulatory motifs with mutually exclusive expression states. The classical deterministic picture for cell fate determination includes bistability and hysteresis, which enables the persistence of the acquired cellular state after withdrawal of the stimulus, ensuring a robust cellular response. However, stochasticity inherent to gene expression dynamics is not compatible with hysteresis, since the stationary solution of the governing Chemical Master Equation does not depend on the initial conditions. We provide a quantitative description of a transient hysteresis phenomenon reconciling experimental evidence of hysteretic behaviour in gene regulatory networks with inherent stochasticity: under sufficiently slow dynamics hysteresis is transient. We quantify this with an estimate of the convergence rate to the equilibrium and introduce a natural landscape capturing system’s evolution that, unlike traditional cell fate potential landscapes, is compatible with coexistence at the microscopic level.

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Engineering of a synthetic quadrastable gene network to approach Waddington landscape and cell fate determination

eLife ◽

10.7554/elife.23702 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 39

Author(s):

Fuqing Wu ◽

Ri-Qi Su ◽

Ying-Cheng Lai ◽

Xiao Wang

Keyword(s):

Cell Fate ◽

Regulatory Networks ◽

Cell Fate Determination ◽

Final States ◽

Cell Fates ◽

Fate Determination ◽

Cellular Decision Making ◽

Distinct Cell ◽

Model Predictions ◽

Gene Regulatory

The process of cell fate determination has been depicted intuitively as cells travelling and resting on a rugged landscape, which has been probed by various theoretical studies. However, few studies have experimentally demonstrated how underlying gene regulatory networks shape the landscape and hence orchestrate cellular decision-making in the presence of both signal and noise. Here we tested different topologies and verified a synthetic gene circuit with mutual inhibition and auto-activations to be quadrastable, which enables direct study of quadruple cell fate determination on an engineered landscape. We show that cells indeed gravitate towards local minima and signal inductions dictate cell fates through modulating the shape of the multistable landscape. Experiments, guided by model predictions, reveal that sequential inductions generate distinct cell fates by changing landscape in sequence and hence navigating cells to different final states. This work provides a synthetic biology framework to approach cell fate determination and suggests a landscape-based explanation of fixed induction sequences for targeted differentiation.

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