scholarly journals Cryptic genetic variation in a heat shock protein modifies the outcome of a mutation affecting epidermal stem cell development in C. elegans

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sneha L. Koneru ◽  
Mark Hintze ◽  
Dimitris Katsanos ◽  
Michalis Barkoulas
Keyword(s):  
Genetic Variation ◽  
Stem Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Fate ◽  
Cell Development ◽  
Wnt Signalling ◽  
Single Amino Acid ◽  
Cryptic Genetic Variation ◽  
Seam Cell

AbstractA fundamental question in medical genetics is how the genetic background modifies the phenotypic outcome of mutations. We address this question by focusing on the seam cells, which display stem cell properties in the epidermis of Caenorhabditis elegans. We demonstrate that a putative null mutation in the GATA transcription factor egl-18, which is involved in seam cell fate maintenance, is more tolerated in the CB4856 isolate from Hawaii than the lab reference strain N2 from Bristol. We identify multiple quantitative trait loci (QTLs) underlying the difference in phenotype expressivity between the two isolates. These QTLs reveal cryptic genetic variation that reinforces seam cell fate through potentiating Wnt signalling. Within one QTL region, a single amino acid deletion in the heat shock protein HSP-110 in CB4856 is sufficient to modify Wnt signalling and seam cell development, highlighting that natural variation in conserved heat shock proteins can shape phenotype expressivity.

scholarly journals Cryptic genetic variation in a heat shock protein shapes the expressivity of a mutation affecting stem cell behaviour in C. elegans

2020 ◽  
Author(s):  
Sneha L. Koneru ◽  
Mark Hintze ◽  
Dimitris Katsanos ◽  
Michalis Barkoulas
Keyword(s):  
Genetic Variation ◽  
Stem Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Fate ◽  
Single Amino Acid ◽  
Cryptic Genetic Variation ◽  
C Elegans ◽  
Seam Cell ◽  
The Difference

AbstractA fundamental question in medical genetics is how the genetic background modifies the phenotypic outcome of key mutations. We address this question by focusing on the epidermal seam cells, which display stem cell properties in Caenorhabditis elegans. We demonstrate that a null mutation in the GATA transcription factor egl-18, which is involved in seam cell fate maintenance, is more tolerated and thus has lower expressivity in the divergent CB4856 isolate from Hawaii than the lab reference strain N2 from Bristol. We identify multiple quantitative trait loci (QTLs) underlying the difference in mutation expressivity between the two isolates. These QTLs reveal cryptic genetic variation, which acts to reinforce seam cell fate through potentiating Wnt signalling. Within one QTL region, a single amino acid deletion in the heat shock protein HSP-110 in CB4856 lowers egl-18 mutation expressivity. Our work underscores that natural variation in conserved heat shock proteins can shape mutation expressivity.

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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sneha L. Koneru ◽  
Fu Xiang Quah ◽  
Ritobrata Ghose ◽  
Mark Hintze ◽  
Nicola Gritti ◽  
...  
Keyword(s):  
Stem Cell ◽  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Single Molecule ◽  
Phenotypic Variability ◽  
Low Frequency ◽  
Time Lapse ◽  
Cell Number ◽  
Seam Cell ◽  
Neuronal Tissues

AbstractDevelopmental 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.

scholarly journals Heat shock protein DNAJA1 stabilizes PIWI proteins to support regeneration and homeostasis of planarian Schmidtea mediterranea

2019 ◽  
Vol 294 (25) ◽  
pp. 9873-9887 ◽  
Author(s):  
Chen Wang ◽  
Zhen-Zhen Yang ◽  
Fang-Hao Guo ◽  
Shuo Shi ◽  
Xiao-Shuai Han ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Adult Stem Cells ◽  
Target Genes ◽  
Human Gastric Cancer ◽  
Piwi Protein ◽  
Schmidtea Mediterranea ◽  
Functional Link

PIWI proteins are key regulators of germline and somatic stem cells throughout different evolutionary lineages. However, how PIWI proteins themselves are regulated remains largely unknown. To identify candidate proteins that interact with PIWI proteins and regulate their stability, here we established a yeast two-hybrid (Y2H) assay in the planarian species Schmidtea mediterranea. We show that DNAJA1, a heat shock protein 40 family member, interacts with the PIWI protein SMEDWI-2, as validated by the Y2H screen and co-immunoprecipitation assays. We found that DNAJA1 is enriched in planarian adult stem cells, the nervous system, and intestinal tissues. DNAJA1-knockdown abolished planarian regeneration and homeostasis, compromised stem cell maintenance and PIWI-interacting RNA (piRNA) biogenesis, and deregulated SMEDWI-1/2 target genes. Mechanistically, we observed that DNAJA1 is required for the stability of SMEDWI-1 and SMEDWI-2 proteins. Furthermore, we noted that human DNAJA1 binds to Piwi-like RNA-mediated gene silencing 1 (PIWIL1) and is required for PIWIL1 stability in human gastric cancer cells. In summary, our results reveal not only an evolutionarily conserved functional link between PIWI and DNAJA1 that is essential for PIWI protein stability and piRNA biogenesis, but also an important role of DNAJA1 in the control of proteins involved in stem cell regulation.

scholarly journals Stem Cell-Like Dog Placenta Cells Afford Neuroprotection against Ischemic Stroke Model via Heat Shock Protein Upregulation

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e76329 ◽  
Author(s):  
SeongJin Yu ◽  
Naoki Tajiri ◽  
Nick Franzese ◽  
Max Franzblau ◽  
EunKyung Bae ◽  
...  
Keyword(s):  
Stem Cell ◽  
Ischemic Stroke ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Stroke Model
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