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

Shu Jun Zhu,Ko W Currie,Changjiang Xu,Stephanie E Hallows,Bret J Pearson

doi:10.7554/elife.07025

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.

Highlights

Adult stem cells (ASCs) are responsible for all tissue turnover in humans, which has been estimated to be approximately 1010 cells per day (Reed, 1999)
Due to the well-known function of MEX3 in mediating asymmetric cell fates during Caenorhabditis elegans embryogenesis (Draper et al, 1996), we propose that Smed-mex3-1 mediates a similar process in planarian stem cell lineages
To identify transcripts enriched in the X2 cell fraction, we used the program DESeq (Anders and Huber, 2010) to compare RNA-deep sequencing (RNAseq) from purified X1 and X2 cells vs whole irradiated animals at 7 days after exposure to 60–100 Gray (Gy) of γ-irradiation (Anders and Huber, 2010; Solana et al, 2012; Fernandes et al, 2014)

Summary

Introduction

Adult stem cells (ASCs) are responsible for all tissue turnover in humans, which has been estimated to be approximately 1010 cells per day (Reed, 1999) This feat is achieved through a delicate balance of proliferation and differentiation, in order to maintain a stable stem cell population while replacing the exact number and type of cells lost to cell turnover or injury. Other stem cell types can use a combination of mechanisms, such as in the mammalian postnatal cortex of the brain where Hedgehog signaling maintains stem cell identity, and asymmetric segregation of RNA-binding protein complexes and cellular processes determines cell fate choice

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Results

Conclusion