Developmental Signals - Nanog: Difference between revisions
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==Introduction== | ==Introduction== | ||
[[File:Human-_spermatozoa_NANOG_expression_01.jpg|thumb|Human testis NANOG expression | [[File:Human-_spermatozoa_NANOG_expression_01.jpg|thumb|Human testis NANOG expression{{#pmid:20539761|PMID20539761}}]] | ||
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. | NANOG ({{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 | First identified in mouse ES cells in a 2003 study{{#pmid:12787505|PMID12787505}}, the author (Chambers) named the factor after an Irish myth, ''Tír na nÓg'' ("Land of the Young") as it makes stem cells immortal. | ||
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* ''' | * '''Estrogen-related receptor-beta (Esrrb) Complementation Rescues Development of Nanog-Null Germ Cells'''{{#pmid:29320730|PMID29320730}} "The transcription factors (TFs) Nanog and Esrrb play important roles in embryonic stem cells (ESCs) and during primordial germ-cell (PGC) development. Esrrb is a positively regulated direct target of NANOG in ESCs that can substitute qualitatively for Nanog function in ESCs. Whether this functional substitution extends to the germline is unknown. Here, we show that germline deletion of Nanog reduces PGC numbers 5-fold at midgestation. Despite this quantitative depletion, Nanog-null PGCs can complete germline development in contrast to previous findings. PGC-like cell (PGCLC) differentiation of Nanog-null ESCs is also impaired, with Nanog-null PGCLCs showing decreased proliferation and increased apoptosis. However, induced expression of Esrrb restores PGCLC numbers as efficiently as Nanog. These effects are recapitulated in vivo: knockin of Esrrb to Nanog restores PGC numbers to wild-type levels and results in fertile adult mice. These findings demonstrate that Esrrb can replace Nanog function in germ cells." [http://omim.org/entry/602167 OMIM - ESRRB] | ||
* ''' | * '''The primary role of zebrafish nanog is in extra-embryonic tissue'''{{#pmid:29180571|PMID29180571}} "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]] | ||
* '''Phosphorylation stabilizes Nanog by promoting its interaction with Pin1''' | * '''Multiple phases in regulation of Nanog expression during pre-implantation development'''{{#pmid:26660234|PMID26660234}} "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]] | ||
* '''Nanog variability and pluripotency regulation of embryonic stem cells''' | |||
* '''Phosphorylation stabilizes Nanog by promoting its interaction with Pin1'''{{#pmid:20622153|PMID20622153}} "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'''{{#pmid:20574542|PMID20574542}} "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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Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Nanog ''Nanog''] | Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Nanog ''Nanog''] | ||
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==Human NANOG Family== | ==Human NANOG Family== | ||
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===Blastocyst - Inner Cell Mass=== | ===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. | In the early mouse embryo, Nano expression appears to be related to maintain of pluripotency in the blastocyst inner cell mass epiblast layer.{{#pmid:26660234|PMID26660234}} | ||
Nanog expression pattern four phases: | Nanog expression pattern four phases: | ||
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===Spermatogenesis=== | ===Spermatogenesis=== | ||
The cartoons below show nanog expression in mouse and dog during spermatogenesis. | The cartoons below show nanog expression in mouse and dog during spermatogenesis.{{#pmid:20539761|PMID20539761}} | ||
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| [[File:Mouse- spermatozoa NANOG expression.jpg|600px]] | | [[File:Mouse- spermatozoa NANOG expression.jpg|600px]] | ||
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===Reviews=== | ===Reviews=== | ||
{{#pmid:28977693}} | |||
{{#pmid:28684962}} | |||
{{#pmid:27877089}} | |||
===Search Pubmed=== | ===Search Pubmed=== |
Latest revision as of 11:40, 27 April 2020
Embryology - 15 Jun 2024 Expand to Translate |
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Introduction
NANOG (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.
Factor Links: AMH | hCG | BMP | sonic hedgehog | bHLH | HOX | FGF | FOX | Hippo | LIM | Nanog | NGF | Nodal | Notch | PAX | retinoic acid | SIX | Slit2/Robo1 | SOX | TBX | TGF-beta | VEGF | WNT | Category:Molecular |
Some Recent Findings
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More recent papers |
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This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.
More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Nanog |
Older papers |
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Human NANOG Family
Nanog belongs to the NKL subclass homeoboxes and pseudogenes.
Table - Human Nanog Family - pseudogenes | ||||
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 | ||
NANOG P6 | Nanog homeobox pseudogene 6 | 10q24.2 | ||
NANOG P7 | Nanog homeobox pseudogene 7 | NANOGP3 | 14q32.12 | |
NANOG P8 | Nanog homeobox retrogene P8 | 15q14 | ||
NANOG P9 | Nanog homeobox pseudogene 9 | Xq12 | ||
NANOG P10 | Nanog homeobox pseudogene 10 | Xp11.3 | ||
NANOG P11 | Nanog homeobox pseudogene 11 | 6q25.2 | ||
Links: Developmental Signals - Nanog | OMIM | HGNC | Tbx Family |
Human NANOG Family | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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.[5]
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.[1]
Signaling Pathway
Two-level process for the induction of stem cell differentiation[7] |
References
- ↑ 1.0 1.1 Kuijk EW, de Gier J, Lopes SM, Chambers I, van Pelt AM, Colenbrander B & Roelen BA. (2010). A distinct expression pattern in mammalian testes indicates a conserved role for NANOG in spermatogenesis. PLoS ONE , 5, e10987. PMID: 20539761 DOI.
- ↑ Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S & Smith A. (2003). Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell , 113, 643-55. PMID: 12787505 DOI.
- ↑ Zhang M, Leitch HG, Tang WWC, Festuccia N, Hall-Ponsele E, Nichols J, Surani MA, Smith A & Chambers I. (2018). Esrrb Complementation Rescues Development of Nanog-Null Germ Cells. Cell Rep , 22, 332-339. PMID: 29320730 DOI.
- ↑ Gagnon JA, Obbad K & Schier AF. (2018). The primary role of zebrafishnanogis in extra-embryonic tissue. Development , 145, . PMID: 29180571 DOI.
- ↑ 5.0 5.1 Komatsu K & Fujimori T. (2015). Multiple phases in regulation of Nanog expression during pre-implantation development. Dev. Growth Differ. , 57, 648-56. PMID: 26660234 DOI.
- ↑ Moretto-Zita M, Jin H, Shen Z, Zhao T, Briggs SP & Xu Y. (2010). Phosphorylation stabilizes Nanog by promoting its interaction with Pin1. Proc. Natl. Acad. Sci. U.S.A. , 107, 13312-7. PMID: 20622153 DOI.
- ↑ 7.0 7.1 7.2 Glauche I, Herberg M & Roeder I. (2010). Nanog variability and pluripotency regulation of embryonic stem cells--insights from a mathematical model analysis. PLoS ONE , 5, e11238. PMID: 20574542 DOI.
Reviews
Blinka S & Rao S. (2017). Nanog Expression in Embryonic Stem Cells - An Ideal Model System to Dissect Enhancer Function. Bioessays , 39, . PMID: 28977693 DOI.
Marucci L. (2017). Nanog Dynamics in Mouse Embryonic Stem Cells: Results from Systems Biology Approaches. Stem Cells Int , 2017, 7160419. PMID: 28684962 DOI.
Zhang W, Sui Y, Ni J & Yang T. (2016). Insights into theNanoggene: A propeller for stemness in primitive stem cells. Int. J. Biol. Sci. , 12, 1372-1381. PMID: 27877089 DOI.
Search Pubmed
Search Pubmed Now: Nanog
Search OMIM Nanog
External Links
External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.
- Entrez Gene - NANOG Nanog homeobox - Homo sapiens
- OMIM - NANOG
- HGNC - NKL subclass homeoboxes
Glossary Links
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Cite this page: Hill, M.A. (2024, June 15) Embryology Developmental Signals - Nanog. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Developmental_Signals_-_Nanog
- © Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G