Introduction
Human testis NANOG expression
[1]
NANOG plays a central role in regulating self-renewal in pluripotent stem cells and tumor cells. Human NANOG is a transcription factor protein of 305 amino acids with a conserved homeodomain motif that is localized to the nucleus.
First identified in mouse ES cells in a 2003 study[2], the author (Chambers) named the factor after an Irish myth, Tír na nÓg ("Land of the Young") as it makes stem cells immortal.
Some Recent Findings
- The primary role of zebrafish nanog is in extra-embryonic tissue[3] "The role of the zebrafish transcription factor Nanog has been controversial. It has been suggested that Nanog is primarily required for the proper formation of the extra-embryonic yolk syncytial layer (YSL) and only indirectly regulates gene expression in embryonic cells. In an alternative scenario, Nanog has been proposed to directly regulate transcription in embryonic cells during zygotic genome activation. To clarify the roles of Nanog, we performed a detailed analysis of zebrafish nanog mutants. Whereas zygotic nanog mutants survive to adulthood, maternal-zygotic (MZnanog) and maternal mutants exhibit developmental arrest at the blastula stage. In the absence of Nanog, YSL formation and epiboly are abnormal, embryonic tissue detaches from the yolk, and the expression of dozens of YSL and embryonic genes is reduced. Epiboly defects can be rescued by generating chimeric embryos of MZnanog embryonic tissue with wild-type vegetal tissue that includes the YSL and yolk cell. Notably, cells lacking Nanog readily respond to Nodal signals and when transplanted into wild-type hosts proliferate and contribute to embryonic tissues and adult organs from all germ layers. These results indicate that zebrafish Nanog is necessary for proper YSL development but is not directly required for embryonic cell differentiation." Zebrafish Development | Yolk Sac
- Multiple phases in regulation of Nanog expression during pre-implantation development[4] "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." Morula | Blastocyst | Mouse Development
- Phosphorylation stabilizes Nanog by promoting its interaction with Pin1[5]"Here we show that Nanog, a transcription factor crucial for the self-renewal of ESCs, is phosphorylated at multiple Ser/Thr-Pro motifs. This phosphorylation promotes the interaction between Nanog and the prolyl isomerase Pin1, leading to Nanog stabilization by suppressing its ubiquitination. Inhibition of Pin1 activity or disruption of Pin1-Nanog interaction in ESCs suppresses their capability to self-renew and to form teratomas in immunodeficient mice. Therefore, in addition to the stringent transcriptional regulation of Nanog, the expression level of Nanog is also modulated by posttranslational mechanisms."
- Nanog variability and pluripotency regulation of embryonic stem cells[6]"The expression of the transcription factors Oct4, Sox2, and Nanog is commonly associated with pluripotency of mouse embryonic stem (ES) cells. However, recent observations suggest that ES cell populations are heterogeneous with respect to the expression of Nanog and that individual ES cells reversibly change their Nanog expression level."
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More recent papers
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Search term: Nanog
<pubmed limit=5>Nanog</pubmed>
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Human NANOG Family
Nanog belongs to the NKL subclass homeoboxes and pseudogenes.
Table - Human Nanog Family - pseudogenes
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Approved Symbol
|
Approved Name
|
Previous Symbols
|
Chromosome
|
NANOG |
Nanog homeobox |
FLJ12581, FLJ40451 |
12p13.31 |
|
NANOG P1 |
Nanog homeobox pseudogene 1 |
NANOG2 |
12p13.31 |
|
NANOG P2 |
Nanog homeobox pseudogene 2 |
NANOGP4 |
2q36.1 |
|
NANOG P3 |
Nanog homeobox pseudogene 3 |
|
6p12.1 |
|
NANOG P4 |
Nanog homeobox pseudogene 4 |
NANOGP2 |
7p14.3 |
|
NANOG P5 |
Nanog homeobox pseudogene 5 |
|
9q31.1 |
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NANOG P6 |
Nanog homeobox pseudogene 6 |
|
10q24.2 |
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NANOG P7 |
Nanog homeobox pseudogene 7 |
NANOGP3 |
14q32.12 |
|
NANOG P8 |
Nanog homeobox retrogene P8 |
|
15q14 |
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NANOG P9 |
Nanog homeobox pseudogene 9 |
|
Xq12 |
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NANOG P10 |
Nanog homeobox pseudogene 10 |
|
Xp11.3 |
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NANOG P11 |
Nanog homeobox pseudogene 11 |
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6q25.2 |
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Links: Developmental Signals - Nanog | OMIM | HGNC | Tbx Family
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Human NANOG Family
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Table - Human Nanog Family - pseudogenes
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Approved Symbol
|
Approved Name
|
Previous Symbols
|
Chromosome
|
NANOG |
Nanog homeobox |
FLJ12581, FLJ40451 |
12p13.31 |
|
NANOG P1 |
Nanog homeobox pseudogene 1 |
NANOG2 |
12p13.31 |
|
NANOG P2 |
Nanog homeobox pseudogene 2 |
NANOGP4 |
2q36.1 |
|
NANOG P3 |
Nanog homeobox pseudogene 3 |
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6p12.1 |
|
NANOG P4 |
Nanog homeobox pseudogene 4 |
NANOGP2 |
7p14.3 |
|
NANOG P5 |
Nanog homeobox pseudogene 5 |
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9q31.1 |
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NANOG P6 |
Nanog homeobox pseudogene 6 |
|
10q24.2 |
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NANOG P7 |
Nanog homeobox pseudogene 7 |
NANOGP3 |
14q32.12 |
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NANOG P8 |
Nanog homeobox retrogene P8 |
|
15q14 |
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NANOG P9 |
Nanog homeobox pseudogene 9 |
|
Xq12 |
|
NANOG P10 |
Nanog homeobox pseudogene 10 |
|
Xp11.3 |
|
NANOG P11 |
Nanog homeobox pseudogene 11 |
|
6q25.2 |
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Links: Developmental Signals - Nanog | OMIM | HGNC | Tbx Family
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- Links: HGNC - NKL subclass homeoboxes
Classification
Functions
Required for embryonic stem cell self-renewal.
Blastocyst - Inner Cell Mass
In the early mouse embryo, Nano expression appears to be related to maintain of pluripotency in the blastocyst inner cell mass epiblast layer.[4]
Nanog expression pattern four phases:
- cleavage stages - very low levels
- morula stage - increased stochastically, no correlation with future cell fates.
- blastocyst stage (after 32-cell stage) - inner cell mass expression was up-regulated.
- blastocyst stage onwards - primitive endoderm repressed in an FGF signalling-dependent manner.
- Links: Morula | Blastocyst | Mouse Development | FGF
Spermatogenesis
The cartoons below show nanog expression in mouse and dog during spermatogenesis.[7]
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Each column represents the combination of different cell types that are present in seminiferous tubules at that specific stage.
Cell types that express NANOG are outlined in red and cell types that do not express NANOG have black and grey symbols.
Legend
- 1–16 = steps in spermiogenesis
- In = intermediate spermatogonia
- B = type B spermatogonia
- Pl = pre-leptotene stage
- L = leptotene stage
- Z = zygotene stage
- P = pachytene stage
- D = diplotene stage
- 2nd = generation of secondary spermatocytes
- Roman figures = stage of the epithelial cycle
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Signaling Pathway
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Two-level process for the induction of stem cell differentiation[6]
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References
- ↑ <pubmed>20539761</pubmed>
- ↑ <pubmed>12787505</pubmed>
- ↑ <pubmed>29180571</pubmed>
- ↑ 4.0 4.1 <pubmed>26660234</pubmed>
- ↑ <pubmed>20622153</pubmed>
- ↑ 6.0 6.1 6.2 <pubmed>20574542</pubmed>| PLoS One
- ↑ <pubmed>20539761</pubmed>| PLoS One.
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Cite this page: Hill, M.A. (2024, March 29) Embryology Developmental Signals - Nanog. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Developmental_Signals_-_Nanog
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