Regeneration and reprogramming compared.
BACKGROUND
Dedifferentiation 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.


RESULTS
We 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.


CONCLUSIONS
By 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.
Christen
Bea
B
Center for Regenerative Medicine of Barcelona, 08003 Barcelona, Spain.
Robles
Vanesa
V
Raya
Marina
M
Paramonov
Ida
I
Izpisúa Belmonte
Juan Carlos
JC
D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D054337:Cell Dedifferentiation / Q000235:genetics / Q000502:physiology*; D065150:Cellular Reprogramming / Q000235:genetics / Q000502:physiology*; D018274:Electroporation; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000502:physiology; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000502:physiology; D012038:Regeneration / Q000235:genetics / Q000502:physiology*; D055747:SOX Transcription Factors / Q000235:genetics / Q000502:physiology; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology
D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; C085437:Pou5f3 protein, zebrafish; D016271:Proto-Oncogene Proteins c-myc; D055747:SOX Transcription Factors; C544611:Sox2 protein, zebrafish; D029961:Zebrafish Proteins