Mechanisms of pluripotency and epigenetic reprogramming in primordial germ cells: lessons for the conversion of other cell types into the stem cell lineage

Authors: SURESH PALAMADAI KRISHNAN

Abstract: Primordial germ cells (PGCs) provide an excellent tool to better understand ancestor?descendent relationships as well as the efficiency and molecular mechanisms governing pluripotency in the reprogramming of somatic cells, since the latter type of cells have a relatively lower efficiency of conversion to pluripotent cells. This kind of comparison has gained credence from the commonalities regarding the expression of key transcription factors such as octamer-binding transcriptionhttp://en.wikipedia.org/wiki/Transcription_factor factor-4 (Oct3/4), SRY-related HMG box (Sox2), myelocytomatosis (c-Myc), and Nanog, as well as redundancy in terms of Kruppel-like factor 2 (Klf2), Kruppel-like factor 5 (Klf5), estrogen-related receptor beta (Esrrb), and estrogen-related receptor gamma (Esrrg) compensating for the absence of Kruppel-like factor 4 (Klf4). However, the exogenous addition of any one of these factors was found to be important, thereby implying that the expression level is important. L-Myelocytomatosis (L-myc) was shown to improve reprogramming efficiency without affecting tumorigenic potential. Molecular aspects of epigenetic reprogramming during the acquisition of pluripotency, as well as tumorigenic potential, have also been discussed, thus providing an understanding of the factors that can improve the former without increasing the possibility of neoplastic transformation. An improved understanding of the molecular events would pave the way for the development and use of endogenous biomolecules as well as currently available chemical reprogrammers for improving the efficiency of conversion of PGCs into cells of the stem cell lineage. Such chemicals, when adequately tested, can possibly be an alternative to viral vectors, since the introduced transgenes can become oncogenic.

Keywords: Primordial germ cells, stem cells, chemical/genetic reprogramming, pluripotency, transcription factors, epigenetic, induced pluripotent stem cells, embryonic germ cells, embryonic stem cells, epiblast stem cells

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