ArticleThe Journal of biological chemistry2011
Alternative splicing produces Nanog protein variants with different capacities for self-renewal and pluripotency in embryonic stem cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 75 citations in OpenAlex.
- NANOG Proximity Proteomics Maps Neighborhood Hubs Linked to Mesenchymal Stem Cell Stemness and Chromatin Control.Biomolecules · 2026Article
- Article
- Research progress of nanog gene in fish.Molecular genetics and genomics : MGG · 2024Review
- KDM3A and KDM3B Maintain Naïve Pluripotency Through the Regulation of Alternative Splicing.bioRxiv : the preprint server for biology · 2024Article
- Comparative functional genomics identifies unique molecular features of EPSCs.Life science alliance · 2022Article
- Characterization of the Nanog gene involved in the gonadal development in pearlscale angelfish (Centropyge vrolikii).Fish physiology and biochemistry · 2022Article
- Article
- Alternative splicing is a developmental switch for hTERT expression.Molecular cell · 2021Article
- Changes in the phosphorylation of nucleotide metabolism‑associated proteins by leukemia inhibitory factor in mouse embryonic stem cells.Molecular medicine reports · 2021Article
- Regulation of pluripotency and reprogramming by RNA binding proteins.Current topics in developmental biology · 2020Review
- Characterization and Isolation of Very Small Embryonic-like (VSEL) Stem Cells Obtained from Various Human Hematopoietic Cell Sources.Stem cell reviews and reports · 2019Article
- ALDH1 expression correlates with an epithelial-like phenotype and favorable prognosis in lung adenocarcinoma: a study based on immunohistochemistry and mRNA expression data.Journal of cancer research and clinical oncology · 2019Article
- Conserved regulation of RNA processing in somatic cell reprogramming.BMC genomics · 2019Article
- Constructing an Isogenic 3D Human Nephrogenic Progenitor Cell Model Composed of Endothelial, Mesenchymal, and SIX2-Positive Renal Progenitor Cells.Stem cells international · 2019Article
- Deconstructing the pluripotency gene regulatory network.Nature cell biology · 2018Review
- Nanog Expression in Embryonic Stem Cells - An Ideal Model System to Dissect Enhancer Function.BioEssays : news and reviews in molecular, cellular and developmental biology · 2017Review
- Post-transcriptional regulation of the pluripotent state.Current opinion in genetics & development · 2017Review
- Context-Dependent Functions of NANOG Phosphorylation in Pluripotency and Reprogramming.Stem cell reports · 2017Article
- Ground rules of the pluripotency gene regulatory network.Nature reviews. Genetics · 2017Review
- The SIN3A/HDAC Corepressor Complex Functionally Cooperates with NANOG to Promote Pluripotency.Cell reports · 2017Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Embryonic stem (ES) cells are distinguished by their ability to undergo unlimited self-renewal although retaining pluripotency, the capacity to specify cells of all germ layers. Alternative splicing contributes to these biological processes by vastly increasing the protein coding repertoire, enabling genes to code for novel variants that may confer different biological functions. The homeodomain transcription factor Nanog acts collaboratively with core factors Oct4 and Sox2 to govern the maintenance of pluripotency. We have discovered that Nanog is regulated by alternative splicing. Two novel exons and six subexons have been identified that extend the known Nanog gene structure and protein coding capacity. Alternative splicing results in two novel Nanog protein variants with attenuated capacities for self-renewal and pluripotency in ES cells. Our previous results have implicated the C-terminal domain, including the tryptophan-rich (WR) domain of Nanog, to be important for the function of Nanog (Wang, J., Levasseur, D. N., and Orkin, S. H. (2008) Proc. Natl. Acad. Sci. U.S.A. 105, 6326-6331). Using point mutation analyses, serine 2 (Ser-2) of Nanog has been identified as critical for ES cell self-renewal and for stabilizing a pluripotent gene signature. An inducible conditional knock-out was created to test the ability of new Nanog variants to genetically complement Nanog null ES cells. These results reveal for the first time an expanded Nanog protein coding capacity. We further reveal that a short region of the N-terminal domain and a single phosphorylatable Ser-2 is essential for the maintenance of self-renewal and pluripotency, demonstrating that this region of the protein is highly regulated.
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