Regeneration and reprogramming compared

Abstract

BackgroundDedifferentiation occurs naturally in mature cell types during epimorphic regeneration in fish and some amphibians. Dedifferentiation also occurs in the induction of pluripotent stem cells when a set of transcription factors (Oct4, Sox2, Klf4 and c-Myc) is over expressed in mature cell types.ResultsWe hypothesised that there are parallels between dedifferentiation or reprogramming of somatic cells to induced pluripotent stem cells and the natural process of dedifferentiation during epimorphic regeneration. We analysed expression levels of the most commonly used pluripotency associated factors in regenerating and non-regenerating tissue and compared them with levels in a pluripotent reference cell. We found that some of the pluripotency associated factors (oct4/pou5f1, sox2, c-myc, klf4, tert, sall4, zic3, dppa2/4 and fut1, a homologue of ssea1) were expressed before and during regeneration and that at least two of these factors (oct4, sox2) were also required for normal fin regeneration in the zebrafish. However these factors were not upregulated during regeneration as would be expected if blastema cells acquired pluripotency.ConclusionsBy comparing cells from the regeneration blastema with embryonic pluripotent reference cells we found that induced pluripotent stem and blastema cells do not share pluripotency. However, during blastema formation some of the key reprogramming factors are both expressed and are also required for regeneration to take place. We therefore propose a link between partially reprogrammed induced pluripotent stem cells and the half way state of blastema cells and suggest that a common mechanism might be regulating these two processes.

Members of the NODE (Nanog and Oct4-associated deacetylase) complex and SOX-2 promote the initiation of a natural cellular reprogramming event in vivo

“…Furthermore, our data raise the intriguing possibility that pluripotent reprogramming borrows to some extent from mechanisms at work during natural reprogramming events. In further support of this possibility, Sall4, Oct4, and Sox2 are expressed during fin regeneration in fish or Xenopus, a process that requires dedifferentiation of the tissue cells surrounding the amputation site, and Oct4 and Sox2 are necessary for regeneration to take place (34,35). Our studies highlight a unique function and association for these factors in an in vivo single-cell reprogramming event that could be promising for fundamental developmental biology, regenerative medicine, and cancer therapies.…”

Dedifferentiation and the role of sall4 in reprogramming and patterning during amphibian limb regeneration

“…Like previous studies, that of Kragl et al (2009) found evidence of plasticity only among ''fibroblasts,'' with labeled cells of dermis contributing to other connective tissue types in the regenerate, including tendons and cartilage. Overall, the evidence from regeneration studies in amphibians indicates that blastema cells are not pluripotent but at best only multipotent (Christen et al, 2010).…”

“…The mechanisms that allow dedifferentiation after tissue injury and the plasticity or reprogramming potential of dedifferentiated limb cells are of key importance in the field of vertebrate regeneration and recent work in this field has been reviewed by several investigators (Brockes and Kumar, 2002;Odelberg, 2005;Straube and Tanaka, 2006;Stocum and Zupanc, 2008;Tsonis, 2008;Christen et al, 2010;Tamura et al, 2010). The present review addresses two questions about dedifferentiation in regenerating amphibian limbs, which are discussed in light of new studies in other models of regeneration or cell reprogramming.…”

Thyroid Hormone Activates Protein Arginine Methyltransferase 1 Expression by Directly Inducing c-Myc Transcription during Xenopus Intestinal Stem Cell Development

“…The KF330 and KF331 primers for PRMT1 were used for SYBR Green PCR. The primers for EF1␣ and c-Myc were as published (61,62).…”