Talk:Developmental Signals - Nanog

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On this website the Discussion Tab or "talk pages" for a topic has been used for several purposes: References - recent and historic that relates to the topic Additional topic information - currently prepared in draft format Links - to related webpages Topic page - an edit history as used on other Wiki sites Lecture/Practical - student feedback Student Projects - online project discussions. Links: Pubmed Most Recent | Reference Tutorial | Journal Searches Glossary Links Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link Cite this page: Hill, M.A. (2024, May 19) Embryology Developmental Signals - Nanog. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Developmental_Signals_-_Nanog

2015

Reversible transformation and de-differentiation of human cells derived from induced pluripotent stem cell teratomas

Hum Cell. 2015 Jun 12. [Epub ahead of print]

Kamada M1, Mitsui Y, Matsuo T, Takahashi T.

Abstract

We first aimed to generate transformed cell lines from a human induced pluripotent stem cell (hiPSC)-teratoma, and then examined the tumorigenic risks of the differentiated cells from hiPSC explant, because hiPSC-derivatives give rise to tumors in immune-deficient mice when transplanted. The colonies isolated from sparse cultures of hiPSC-teratoma cells expressed NANOG and OCT3/4 strongly, and telomerase reverse transcriptase (TERT) weakly. However, soft agar assay demonstrated that only one of them generated colonies in the gel, though hiPSCs, hTERT-transfected immortal cells, and its oncogene-transfected cells did not form any colonies. Furthermore, none of colonies isolated from the soft agar gel on primary culture (passage 0) of teratoma cells, expressed NANOG and OCT3/4 in the expanded cultures. The second soft agar assay on the colony-derived cells was unexpectedly negative. The cumulative growth curve, telomere shortening, and senescence-associated β-galactosidase (SA β-gal) staining confirmed the mortality of these cells, suggesting their reversible transformation. By using medium for embryonic stem cell (ESC medium) after MCDB 131 (MCDB) medium, the differentiated culture cells derived from hiPSC-teratoma converted into the cells expressing undifferentiated marker proteins, which lost afterwords even in ESC medium with feeder SNL76/7. The reversibility of transformation and de-differentiation suggest that tumorigenic risks of differentiated cells arise when they are exposed to suitable niches in vivo. Thus, removal of only the undifferentiated cells from iPSC-derivatives before transplantation does not solve the problem. Elucidation of mechanisms of reversibility and control of epigenetic changes is discussed as a safety bottleneck for hiPSC therapy.

PMID 26069211