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A mex3 homolog is required for differentiation during planarian stem cell lineage development.

Zhu SJ, Hallows SE, Currie KW, Xu C, Pearson BJ - Elife (2015)

Bottom Line: In this study, we used transcriptional profiling of irradiation-sensitive and irradiation-insensitive cell populations and RNA interference (RNAi) functional screening to uncover markers and regulators of postmitotic progeny.We also demonstrated the utility of using mex3-1(RNAi) animals to identify additional progenitor markers.These results identified mex3-1 as a cell fate regulator, broadly required for differentiation, and suggest that mex3-1 helps to mediate the balance between ASC self-renewal and commitment.

View Article: PubMed Central - PubMed

Affiliation: Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Canada.

ABSTRACT
Neoblasts are adult stem cells (ASCs) in planarians that sustain cell replacement during homeostasis and regeneration of any missing tissue. While numerous studies have examined genes underlying neoblast pluripotency, molecular pathways driving postmitotic fates remain poorly defined. In this study, we used transcriptional profiling of irradiation-sensitive and irradiation-insensitive cell populations and RNA interference (RNAi) functional screening to uncover markers and regulators of postmitotic progeny. We identified 32 new markers distinguishing two main epithelial progenitor populations and a planarian homolog to the MEX3 RNA-binding protein (Smed-mex3-1) as a key regulator of lineage progression. mex3-1 was required for generating differentiated cells of multiple lineages, while restricting the size of the stem cell compartment. We also demonstrated the utility of using mex3-1(RNAi) animals to identify additional progenitor markers. These results identified mex3-1 as a cell fate regulator, broadly required for differentiation, and suggest that mex3-1 helps to mediate the balance between ASC self-renewal and commitment.

No MeSH data available.


Related in: MedlinePlus

Predicted protein alignments of the PROG family that are irradiation-sensitive.An alignment of the 17 PROG family genes used in this study is shown using the tool MUSCLE. Blue shading of residues reflects conservation, which is also plotted below the alignment in the ‘conservation’ plot.DOI:http://dx.doi.org/10.7554/eLife.07025.005
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fig1s2: Predicted protein alignments of the PROG family that are irradiation-sensitive.An alignment of the 17 PROG family genes used in this study is shown using the tool MUSCLE. Blue shading of residues reflects conservation, which is also plotted below the alignment in the ‘conservation’ plot.DOI:http://dx.doi.org/10.7554/eLife.07025.005

Mentions: Interestingly, the predicted proteins encoded by prog-1 and prog-2 do not have clear homology to genes in other animals, including the genomes of other sequenced flatworms (Echinococcus multilocularis, Schistosoma mansoni, Macrostomum lignano—www.macgenome.org) (Berriman et al., 2009; Zheng et al., 2013). However, we observed that they had low similarity to each other and represented a family of at least 24 distinct members across multiple transcriptomes in S. mediterranea, 15 of which were represented in the top 100 X2-enriched gene set (Sandmann et al., 2011; Solana et al., 2012; Currie and Pearson, 2013; Vogg et al., 2014). Translations of the predicted open reading frames (average size 179 amino acids) for these 15 prog-related genes were aligned and analyzed by protein domain prediction software SMART (Figure 1—figure supplement 2) (Schultz et al., 1998; Letunic et al., 2014). The only motif that could be detected was a signal sequence at the N-terminal end of the predicted proteins, suggesting that these proteins are secreted. These PROG-1/2 homologous genes were then named in a numbered sequence based on their closest homolog (e.g., prog-1-1, prog-2-1).


A mex3 homolog is required for differentiation during planarian stem cell lineage development.

Zhu SJ, Hallows SE, Currie KW, Xu C, Pearson BJ - Elife (2015)

Predicted protein alignments of the PROG family that are irradiation-sensitive.An alignment of the 17 PROG family genes used in this study is shown using the tool MUSCLE. Blue shading of residues reflects conservation, which is also plotted below the alignment in the ‘conservation’ plot.DOI:http://dx.doi.org/10.7554/eLife.07025.005
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4507787&req=5

fig1s2: Predicted protein alignments of the PROG family that are irradiation-sensitive.An alignment of the 17 PROG family genes used in this study is shown using the tool MUSCLE. Blue shading of residues reflects conservation, which is also plotted below the alignment in the ‘conservation’ plot.DOI:http://dx.doi.org/10.7554/eLife.07025.005
Mentions: Interestingly, the predicted proteins encoded by prog-1 and prog-2 do not have clear homology to genes in other animals, including the genomes of other sequenced flatworms (Echinococcus multilocularis, Schistosoma mansoni, Macrostomum lignano—www.macgenome.org) (Berriman et al., 2009; Zheng et al., 2013). However, we observed that they had low similarity to each other and represented a family of at least 24 distinct members across multiple transcriptomes in S. mediterranea, 15 of which were represented in the top 100 X2-enriched gene set (Sandmann et al., 2011; Solana et al., 2012; Currie and Pearson, 2013; Vogg et al., 2014). Translations of the predicted open reading frames (average size 179 amino acids) for these 15 prog-related genes were aligned and analyzed by protein domain prediction software SMART (Figure 1—figure supplement 2) (Schultz et al., 1998; Letunic et al., 2014). The only motif that could be detected was a signal sequence at the N-terminal end of the predicted proteins, suggesting that these proteins are secreted. These PROG-1/2 homologous genes were then named in a numbered sequence based on their closest homolog (e.g., prog-1-1, prog-2-1).

Bottom Line: In this study, we used transcriptional profiling of irradiation-sensitive and irradiation-insensitive cell populations and RNA interference (RNAi) functional screening to uncover markers and regulators of postmitotic progeny.We also demonstrated the utility of using mex3-1(RNAi) animals to identify additional progenitor markers.These results identified mex3-1 as a cell fate regulator, broadly required for differentiation, and suggest that mex3-1 helps to mediate the balance between ASC self-renewal and commitment.

View Article: PubMed Central - PubMed

Affiliation: Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Canada.

ABSTRACT
Neoblasts are adult stem cells (ASCs) in planarians that sustain cell replacement during homeostasis and regeneration of any missing tissue. While numerous studies have examined genes underlying neoblast pluripotency, molecular pathways driving postmitotic fates remain poorly defined. In this study, we used transcriptional profiling of irradiation-sensitive and irradiation-insensitive cell populations and RNA interference (RNAi) functional screening to uncover markers and regulators of postmitotic progeny. We identified 32 new markers distinguishing two main epithelial progenitor populations and a planarian homolog to the MEX3 RNA-binding protein (Smed-mex3-1) as a key regulator of lineage progression. mex3-1 was required for generating differentiated cells of multiple lineages, while restricting the size of the stem cell compartment. We also demonstrated the utility of using mex3-1(RNAi) animals to identify additional progenitor markers. These results identified mex3-1 as a cell fate regulator, broadly required for differentiation, and suggest that mex3-1 helps to mediate the balance between ASC self-renewal and commitment.

No MeSH data available.


Related in: MedlinePlus