Targeted DamID in<i>C. elegans</i>reveals a role for LIN-22 and NHR-25 in epidermal cell differentiation

Katsanos, Dimitris; Barkoulas, Michalis

doi:10.1101/2020.12.17.423252

Cited by 3 publications

References 104 publications

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A role for the fusogen eff-1 in epidermal stem cell number robustness in Caenorhabditis elegans

Koneru

Quah

Ghose

et al. 2021

Sci Rep

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Developmental patterning in Caenorhabditis elegans is known to proceed in a highly stereotypical manner, which raises the question of how developmental robustness is achieved despite the inevitable stochastic noise. We focus here on a population of epidermal cells, the seam cells, which show stem cell-like behaviour and divide symmetrically and asymmetrically over post-embryonic development to generate epidermal and neuronal tissues. We have conducted a mutagenesis screen to identify mutants that introduce phenotypic variability in the normally invariant seam cell population. We report here that a null mutation in the fusogen eff-1 increases seam cell number variability. Using time-lapse microscopy and single molecule fluorescence hybridisation, we find that seam cell division and differentiation patterns are mostly unperturbed in eff-1 mutants, indicating that cell fusion is uncoupled from the cell differentiation programme. Nevertheless, seam cell losses due to the inappropriate differentiation of both daughter cells following division, as well as seam cell gains through symmetric divisions towards the seam cell fate were observed at low frequency. We show that these stochastic errors likely arise through accumulation of defects interrupting the continuity of the seam and changing seam cell shape, highlighting the role of tissue homeostasis in suppressing phenotypic variability during development.

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A role for the fusogen eff-1 in epidermal stem cell number robustness in Caenorhabditis elegans

Koneru

Quah

Ghose

et al. 2021

Sci Rep

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The SWI/SNF chromatin remodeling assemblies BAF and PBAF differentially regulate cell cycle exit and cellular invasionin vivo

Smith

Xiao

et al. 2021

Preprint

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Chromatin remodeling complexes, such as the SWItching defective/Sucrose Non-Fermenting (SWI/SNF) ATP-dependent chromatin remodeling complex, coordinate metazoan development through broad regulation of chromatin accessibility and transcription, ensuring normal cell cycle control and cellular differentiation in a lineage-specific and temporally restricted manner. Mutations in subunits of chromatin regulating factors are associated with a variety of diseases and cancer metastasis co-opts cellular invasion found in healthy cells during development. Here we utilize Caenorhabditis elegans anchor cell (AC) invasion as an in vivo model to identify the suite of chromatin and chromatin regulating factors (CRFs) that promote cellular invasiveness. We demonstrate that the SWI/SNF ATP-dependent chromatin remodeling complex is a critical regulator of AC invasion, with pleiotropic effects on both G0/G1 cell cycle arrest and activation of invasive machinery. Using targeted protein degradation and RNA interference (RNAi), we show that SWI/SNF contributes to AC invasion in a dose-dependent fashion, with lower levels of activity in the AC corresponding to aberrant cell cycle entry and increased loss of invasion. Finally, we implicate the SWI/SNF BAF assembly in the regulation of the cell cycle, whereas our data suggests that the SWI/SNF PBAF assembly promotes AC attachment to the basement membrane (BM) and promotes the activation of the invasive machinery. Together these findings demonstrate that the SWI/SNF complex is necessary for two essential components of AC invasion: arresting cell cycle progression and remodeling the BM. The work here provides valuable single-cell mechanistic insight into the contributions of SWI/SNF assembly and subunit-specific disruptions to tumorigenesis and cancer metastasis.

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Gene expression profiling of epidermal cell types in C. elegans using Targeted DamID

et al. 2021

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The epidermis of Caenorhabditis elegans is an essential tissue for survival as it contributes to the formation of the cuticle barrier, as well as facilitates developmental progression and animal growth. Most of the epidermis consists of the hyp7 hypodermal syncytium, the nuclei of which are largely generated by the seam cells that exhibit stem cell-like behaviour during development. How the seam cell progenitors differ transcriptionally from the differentiated hypodermis is poorly understood. Here, we introduce Targeted DamID (TaDa) in C. elegans as a method for identifying genes expressed within a tissue of interest without cell isolation. We show that TaDa signal enrichment profiles can be used to identify genes transcribed in the epidermis and use this method to resolve differences in gene expression between the seam cells and the hypodermis. We finally predict and functionally validate new transcription and chromatin factors acting in seam cell development. These findings provide insights into cell-type-specific gene expression profiles likely associated with epidermal cell fate patterning.

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Targeted DamID inC. elegansreveals a role for LIN-22 and NHR-25 in epidermal cell differentiation

Cited by 3 publications

References 104 publications

A role for the fusogen eff-1 in epidermal stem cell number robustness in Caenorhabditis elegans

A role for the fusogen eff-1 in epidermal stem cell number robustness in Caenorhabditis elegans

The SWI/SNF chromatin remodeling assemblies BAF and PBAF differentially regulate cell cycle exit and cellular invasionin vivo

Gene expression profiling of epidermal cell types in C. elegans using Targeted DamID

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