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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

Analysis of new progeny markers in zfp-1(RNAi) animals.X2-enriched and WThighXlow early and late progeny transcripts identified as potential markers of epithelial progenitors were assessed by WISH in zfp-1(RNAi) animals. Knockdown of zfp-1 has previously been shown to selectively ablate zeta-neoblasts and output of epithelial progenitors, and down-regulate prog-1 and prog-2.DOI:http://dx.doi.org/10.7554/eLife.07025.010
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fig2s4: Analysis of new progeny markers in zfp-1(RNAi) animals.X2-enriched and WThighXlow early and late progeny transcripts identified as potential markers of epithelial progenitors were assessed by WISH in zfp-1(RNAi) animals. Knockdown of zfp-1 has previously been shown to selectively ablate zeta-neoblasts and output of epithelial progenitors, and down-regulate prog-1 and prog-2.DOI:http://dx.doi.org/10.7554/eLife.07025.010

Mentions: Finally, to validate that expression of these genes marked epithelial progenitors, we examined their expression by WISH in zfp-1(RNAi) worms. Knockdown of zfp-1 has been demonstrated to specifically ablate epithelial progenitors and epithelial differentiation, but not the differentiation of other tissue types (van Wolfswinkel et al., 2014). We observed that every new epithelial progenitor marker assessed was down-regulated after zfp-1 RNAi, confirming that these genes were indeed expressed in epithelial progenitors (Figure 2—figure supplement 4). Together, these findings demonstrated that our newly identified transcripts represent markers of the early and late progeny produced by zeta neoblasts and comprise the primary two progenitor populations en route to the epithelium (van Wolfswinkel et al., 2014).


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)

Analysis of new progeny markers in zfp-1(RNAi) animals.X2-enriched and WThighXlow early and late progeny transcripts identified as potential markers of epithelial progenitors were assessed by WISH in zfp-1(RNAi) animals. Knockdown of zfp-1 has previously been shown to selectively ablate zeta-neoblasts and output of epithelial progenitors, and down-regulate prog-1 and prog-2.DOI:http://dx.doi.org/10.7554/eLife.07025.010
© Copyright Policy
Related In: Results  -  Collection

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

fig2s4: Analysis of new progeny markers in zfp-1(RNAi) animals.X2-enriched and WThighXlow early and late progeny transcripts identified as potential markers of epithelial progenitors were assessed by WISH in zfp-1(RNAi) animals. Knockdown of zfp-1 has previously been shown to selectively ablate zeta-neoblasts and output of epithelial progenitors, and down-regulate prog-1 and prog-2.DOI:http://dx.doi.org/10.7554/eLife.07025.010
Mentions: Finally, to validate that expression of these genes marked epithelial progenitors, we examined their expression by WISH in zfp-1(RNAi) worms. Knockdown of zfp-1 has been demonstrated to specifically ablate epithelial progenitors and epithelial differentiation, but not the differentiation of other tissue types (van Wolfswinkel et al., 2014). We observed that every new epithelial progenitor marker assessed was down-regulated after zfp-1 RNAi, confirming that these genes were indeed expressed in epithelial progenitors (Figure 2—figure supplement 4). Together, these findings demonstrated that our newly identified transcripts represent markers of the early and late progeny produced by zeta neoblasts and comprise the primary two progenitor populations en route to the epithelium (van Wolfswinkel et al., 2014).

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