Transcription Factors Active in the Anterior Blastema of Schmidtea mediterranea.

Yoko Suzuki-Horiuchi,Martina Sinn,Carlotta Barlassina,Claudia Ortmeier,Henning Schmitz,Luca Gentile,David Eccles,Sören Moritz

doi:10.3390/biom11121782

Yoko Suzuki-Horiuchi, Martina Sinn + Show 6 more

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https://doi.org/10.3390/biom11121782

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Abstract

Regeneration, the restoration of body parts after injury, is quite widespread in the animal kingdom. Species from virtually all Phyla possess regenerative abilities. Human beings, however, are poor regenerators. Yet, the progress of knowledge and technology in the fields of bioengineering, stem cells, and regenerative biology have fostered major advancements in regenerative medical treatments, which aim to regenerate tissues and organs and restore function. Human induced pluripotent stem cells can differentiate into any cell type of the body; however, the structural and cellular complexity of the human tissues, together with the inability of our adult body to control pluripotency, require a better mechanistic understanding. Planarians, with their capacity to regenerate lost body parts thanks to the presence of adult pluripotent stem cells could help providing such an understanding. In this paper, we used a top-down approach to shortlist blastema transcription factors (TFs) active during anterior regeneration. We found 44 TFs—31 of which are novel in planarian—that are expressed in the regenerating blastema. We analyzed the function of half of them and found that they play a role in the regeneration of anterior structures, like the anterior organizer, the positional instruction muscle cells, the brain, the photoreceptor, the intestine. Our findings revealed a glimpse of the complexity of the transcriptional network governing anterior regeneration in planarians, confirming that this animal model is the perfect playground to study in vivo how pluripotency copes with adulthood.

Highlights

Planarian regeneration lasts approximately two weeks but most of the missing tissues regenerate within one week from amputation
We defined an experimental and analytical setup based on RNA-Seq whose goal was to shortlist transcription factors (TFs) mainly active in the regenerating blastema, either at 3, 6 or both 3 and 6 dpa
Planarian stem cells (SCs) start proliferating in the region next to the wound; post-mitotic early SC progeny accumulate between the proliferating SCs and the wound, and a blastema becomes macroscopically visible at the wound site after

Summary

Introduction

Planarians can regenerate all the missing tissues and organs after amputation, like the central nervous system (CNS) [1,2,3,4,5,6,7,8,9,10], the photoreceptors [11,12,13,14,15,16,17,18,19,20,21], the protonephridia [22,23,24], the intestine [25,26,27,28], and the body wall [29,30,31]. Especially transcriptional regulators, were identified that are involved in planarian regeneration, either regulating its temporal and spatial organization, like MyoD [29], Prep [39], Isl-1 [40], or contributing directly to the cell and tissue functional differentiation, from the exit from pluripotency (e.g., Tcf15) to the terminal differentiation of specific tissues, like the brain, the intestine, the photoreceptors, the protonephridia and the germline [8,14,22,25,41,42,43,44,45]. What is not yet fully understood is how the blastema is temporally and spatially regulated as a whole, and how the regeneration of several structures of the body is concerted

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