Talk:Developmental Signals - Nanog
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Cite this page: Hill, M.A. (2024, June 9) Embryology Developmental Signals - Nanog. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Developmental_Signals_-_Nanog |
2015
Multiple phases in regulation of Nanog expression during pre-implantation development
Dev Growth Differ. 2015 Dec;57(9):648-56. doi: 10.1111/dgd.12244. Epub 2015 Dec 14.
Komatsu K1, Fujimori T1,2.
Abstract
Nanog is a key transcriptional factor for the maintenance of pluripotency of ES cells, iPS cells or cells in early mammalian embryos. The expression of Nanog is mainly localized to the epiblast in the late blastocyst. The Nanog gene expression pattern varies between embryos and between blastomeres during blastocyst formation. In this report, we traced the changes of Nanog expression in each cell in developing preimplantation mouse embryos through time-lapse observation of Nanog-GFP transgenic mouse embryos. The expression pattern of Nanog was classified into four phases depending on the developmental stage. Nanog expression started at very low levels during cleavage stages. It increased stochastically during the morula stage, but its expression level had no clear correlation with future cell fates. After the 32-cell stage, when embryos form the blastocyst cavity, Nanog expression was upregulated mainly in ICM cells while it was repressed in the future primitive endoderm lineage in an FGF signaling-dependent manner in the later stages. These results indicate that there are multiple phases in the transcriptional regulation of Nanog during blastocyst formation. © 2015 Japanese Society of Developmental Biologists. KEYWORDS: Nanog; blastocyst; preimplantation embryo; single cell; time-lapse
PMID 26660234
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
2003
Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells
Cell. 2003 May 30;113(5):643-55.
Chambers I1, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A.
Abstract
Embryonic stem (ES) cells undergo extended proliferation while remaining poised for multilineage differentiation. A unique network of transcription factors may characterize self-renewal and simultaneously suppress differentiation. We applied expression cloning in mouse ES cells to isolate a self-renewal determinant. Nanog is a divergent homeodomain protein that directs propagation of undifferentiated ES cells. Nanog mRNA is present in pluripotent mouse and human cell lines, and absent from differentiated cells. In preimplantation embryos, Nanog is restricted to founder cells from which ES cells can be derived. Endogenous Nanog acts in parallel with cytokine stimulation of Stat3 to drive ES cell self-renewal. Elevated Nanog expression from transgene constructs is sufficient for clonal expansion of ES cells, bypassing Stat3 and maintaining Oct4 levels. Cytokine dependence, multilineage differentiation, and embryo colonization capacity are fully restored upon transgene excision. These findings establish a central role for Nanog in the transcription factor hierarchy that defines ES cell identity. Comment in Nanog: a new recruit to the embryonic stem cell orchestra. [Cell. 2003]
PMID 12787505
