CINXE.COM

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5.1724696046-473375462.1712005244" style="margin: 0 10px;" target="_blank"><img alt="Novus Biologicals products are now on bio-techne.com" src="https://images.novusbio.com/design/ready-to-buy-novus-products-login.png" style="height:120px; width:940px" /></a></div> </div> </div> </div> <div class="clear"></div> <div class="ra-header"><img src="https://images.novusbio.com/design/bannerStemCells02.jpg" class="ra-header" alt="Stem Cell Signaling" /></div> </div> <div class="main grid_4"> <div class="ra-menu"><ul><li><a href="/research-areas/stem-cells">Stem Cell Research</a></li><li><a href="/research-areas/stem-cells/embryonic-stem-cell-markers">Embryonic Stem Cells</a></li><li><a href="/research-areas/stem-cells/hematopoietic-stem-cell-marker">Hematopoietic Stem Cell Markers</a></li><li><a href="/research-areas/stem-cells/induced-pluripotent-stem-cells">Induced Pluripotent Stem Cells (iPSCs)</a></li><li><a href="/research-areas/stem-cells/mesenchymal-stem-cell-markers">Mesenchymal Stem Cells (MSCs)</a></li><li><a href="/research-areas/stem-cells/neural-stem-cell">Neural Stem Cells</a></li><li><a href="/research-areas/stem-cells/resources">Resources</a></li><li><a href="/research-areas/stem-cells/stem-cell-lines.html">Stem Cell Lines</a></li><li class="active"><a href="/research-areas/stem-cells/stem-cell-signaling-pathway">Stem Cell Signaling</a></li></ul></div><div class="ra-publications"><div class="ra-left-header">Publications</div><div class="ra-left-body"><ul class="ra-publist"><li><a href="https://www.tocris.com/literature/product-guides/stem-cell" target="_blank"><img src="https://images.novusbio.com/design/tocris-stem-cell-br2.jpg" /></a></li><li><a href="https://resources.tocris.com/pdfs/literature/posters/stem-cell-workflow-poster-v1-2019.pdf" target="_blank"><img src="https://images.novusbio.com/design/mp-stem-cell-workflow-tocris-thumb.jpg" /></a></li><li><a href="https://resources.tocris.com/pdfs/literature/posters/stemcells-poster-2018.pdf" target="_blank"><img src="https://images.novusbio.com/design/mp-stem-cells-tocris-thumb.jpg" /></a></li></ul></div></div><div class="ra-charities"><div class="ra-left-header">Charities</div><div class="ra-left-body"><span class="ra-button-span"><a href="mailto:marketing@novusbio.com?subject=Charity%20Submission%20for%20Stem+Cell+Signaling" class="ra-button">Submit a Charity</a></span><div class="clear"></div></div></div><div class="ra-events"><div class="ra-left-header">Events</div><div class="ra-left-body"><p class="ra-events-blurb"><span class="ra-events-image"> </span>Submit your event on Stem Cell Signaling Pathway to be featured.</p><span class="ra-button-span"><a href="mailto:marketing@novusbio.com?subject=Event%20Submission%20for%20Stem+Cell+Signaling&body%3DEvent%20Name%3A%0ADescription%3A%0ADates%3A%0ATime%3A%0ALocation%3A%0AMore%20information%20URL%3A%0AImage%20%28please%20attach%20any%20relevant%20images%29" class="ra-button">Submit an Event</a></span><div class="clear"></div></div></div> </div> <div class="main grid_12"> <table cellpadding="6" cellspacing="6"> <tr> <td> <h2>Stem Cell Signaling</h2> <p>Self-renewal and differentiation potential, two key defining stem cell properties, are underscored by a network of transcription factors, epigenetic modifiers and modulating kinase signaling pathways. The Yamanaka factors, which include octamer-binding transcription factor-4 (Oct4), sex-determining region Y-box 2 (Sox2), Kruppel-like factor-4 (Klf4), and c-myelocytomatosis (c-Myc), were shown by <a href="https://www.ncbi.nlm.nih.gov/pubmed/16904174" target="_blank">Takahashi and Yamanaka</a> to play a key role in the maintenance of pluripotency. Their work described for the first time the generation of induced pluripotent stem cells (iPSCs) by exogenous expression of a transcriptional pluripotency program in adult differentiated cells. <a href="/common-name/oct4">Oct4</a>, <a href="/common-name/sox2">Sox2</a> and <a href="/common-name/nanog">Nanog</a> are now commonly considered core pluripotency factors.</p> <br/> <table> <tr> <td> <img src="https://images.novusbio.com/design/oct4-250px.jpg" alt="Expression of core pluripotency factors OCT4, SOX2 and Nanog evaluated by immunocytochemistry in stem cells NTERA-2 and BG01V human embryonic stem cells." title="OCT4 and SOX2 expression in NTERA-2 cells, and Nanog expression in BG01V human embryonic stem cells, ICC."> </td> <td> <img src="https://images.novusbio.com/design/sox2-250px.jpg" alt="Expression of core pluripotency factors OCT4, SOX2 and Nanog evaluated by immunocytochemistry in stem cells NTERA-2 and BG01V human embryonic stem cells." title="OCT4 and SOX2 expression in NTERA-2 cells, and Nanog expression in BG01V human embryonic stem cells, ICC."> </td> <td> <img src="https://images.novusbio.com/design/nanog-250px.jpg" alt="Expression of core pluripotency factors OCT4, SOX2 and Nanog evaluated by immunocytochemistry in stem cells NTERA-2 and BG01V human embryonic stem cells." title="OCT4 and SOX2 expression in NTERA-2 cells, and Nanog expression in BG01V human embryonic stem cells, ICC."> </td> </tr> <tr> <td colspan="3"> <p><em>Immunocytochemistry/Immunofluorescence: (Left) <a href="/products/oct4-antibody-7e7_nbp1-51664">OCT4 Antibody [NBP1-51664] </a>- OCT4 staining in NTERA-2 cells (Green) and actin staining with Alexa Fluor-555 phalloidin (Red). (Middle) <a href="/products/sox2-antibody_nb110-37235">SOX2 Antibody [NB110-37235]</a> - SOX2 staining in NTERA-2 cells with Dylight 488 (Green). Alpha-tubulin and nuclei were counterstained with Dylight 550 (Red) and DAPI (Blue), respectively. (Right) Nanog staining in immersion fixed BG01V human embryonic stem cells with <a href="/products/nanog-antibody_af1997">Goat Anti-Human Nanog Antigen Affinity-purified Polyclonal Antibody (AF1997) </a>detected with the NorthernLights™ 557-conjugated <a href="/products/igg-antibody_nl001">Anti-Goat IgG Secondary Antibody (NL001) </a>(Red) and counterstained with <a href="/products/dapi-solution_nbp2-31156">DAPI</a> (Blue).</em></p> </td> </tr> </table> <br/> <p align="center"> <a href="/search?keywords=stem%20cell%20&category=Support%20Products" class="link_button">View Available mESCs </a> </p> <br/> <h2>How Core Pluripotency Factors Work?</h2> <p align="center"><img src="https://images.novusbio.com/design/core-pluripotency-01.png" alt="Core pluripotency factors OCT4, SOX2 and Nanog interact with other transcriptional regulators for the maintenance of stem cell pluripotency and self-renewal." usemap="#map1" title="Core pluripotency factors OCT4, SOX2 and Nanog interactions."></p> <p><em>Core pluripotency transcription factors interact with each other and with many other transcriptional regulators to maintain stem cell pluripotency. These core factors engage in complex interactions to regulate their own expression and promote the expression of genes which support pluripotency or inhibit those which lead to differentiation.</em></p> <br/> <h2>Kinase Modulating Pathways</h2> <p>Several kinase signal transduction pathways modulate the core pluripotency transcription factors in response to both intrinsic and extrinsic stimuli, preserving stem cell self-renewal and differentiation potential. Synergy between these pathways ensures the maintenance of pluripotency.</p> <p align="center"><img src="https://images.novusbio.com/design/kinase-modulating-pathway-3.png" alt="Several kinase pathways (e.g., WNT and TGF-beta) modulate core pluripotency factors OCT4, SOX2 and Nanog to ensure the maintenance of stem cell pluripotency and self-renewal capacity." usemap="#map2" title="Kinase signaling modulate core pluripotency factors OCT4, SOX2 and Nanog."></p> <br/> <p align="center"> <a href="/pathwaypages.html" class="link_button">View All Signaling Pathways</a> </p> <br/> <p><a href="https://www.tocris.com/pathways/wnt-signaling-pathway" target="_blank">WNT signaling</a>- Involved in the regulation of cellular proliferation, adhesion, and migration. Canonical WNT signaling leads to the stabilization of the transcriptional co-activator beta-catenin. Formation of a nuclear complex between b-catenin and T-cell factor/lymphoid enhancer factor (TCF/LEF) supports the expression of Oct4 and Nanog in pluripotent stem cells (mESC and hESC).</p> <p><a href="/tgfbetapathway">TGF-</a><a href="/tgfbetapathway">b</a><a href="/tgfbetapathway"> signaling</a>- Involved in the regulation of a wide range of cellular processes such as differentiation, proliferation, and programmed cell death. Important for the maintenance of self-renewal and differentiation potential of mESCs and hESCs. For example, canonical TGF-b signaling initiated by BMP4 leads to Smad1/5/8 activation and induction of Inhibitor of DNA-binding/differentiation (Id) proteins for maintenance of mESCs. In contrast, TGF-b signaling initiated by TGF-b and Activin activate Smad2 for maintenance of primed-mESCs and hESCs.</p> <p>LIF signaling- The simultaneous activation of the JAK/<a href="/common-name/stat3">STAT3 </a>and PI3K/<a href="/akt-pathway">AKT</a> pathways plays an important role in the maintenance of mESC pluripotency. Activation of JAK/STAT3 leads to the induction of Klf4 and expression of SOX2, while activation of the PI3K/AKT pathway increases the expression of Nanog by induction of Tbx3.</p> <p><a href="https://www.rndsystems.com/pathways/fgf-signaling-pathways" target="_blank">FGF signaling</a>- Regulates various cellular processes including cell proliferation, migration, differentiation, and survival. Activation of <a href="/mapkerkpathway.html">ERK</a>/MAPK signaling downstream of tyrosine kinase receptor/<a href="/common-name/fgf-basic-fgf2-bfgf">FGF2</a> stimulation is involved in the maintenance of hESC pluripotency. FGF/ERK signaling is not required for mESC maintenance, rather ERK activation leads to the differentiation of mESCs.</p> <br/> <p align="center"> <a href="/research-areas/stem-cells/embryonic-stem-cell-markers" class="link_button">Explore Embryonic Stem Cells</a> </p> <br/> <p align="center"> <a href="/support/bulk-and-custom.html"><img src="https://images.novusbio.com/design/DW_NB_BulkBannerAd_700x366.jpg" alt="Get custom and bulk service support through Novus' team of antibody experts" title="Novus Custom and Bulk Services Banner"></a> </p> <br/> <h3>New ExCellerate™ iPSC Expansion Medium</h3> <p>Supports robust expansion and maintenance of pluripotent stem cell culture for enhanced consistency and reproducibility. </p> <ul> <li>Animal component-free</li> <li>No growth factor supplementation required</li> <li>Stable cell integrity over long term culture</li> </ul> <p style="margin: 20px 0px 30px 0px"><a class="link_button" href="https://www.bio-techne.com/p/cell-culture/excellerate-ipsc-expansion-medium_ccm036" target="_blank">Try our iPSC Expansion Medium</a></p> <br/> <p align="center"> <a href="#top">Back to the Top</a> </p> <br/> <p><strong>Select References</strong></p> <p>Bieberich, E., & Wang, G. (2013). <a href="https://www.intechopen.com/books/pluripotent-stem-cells/molecular-mechanisms-underlying-pluripotency">Molecular Mechanisms Underlying Pluripotency. In </a><a href="https://www.intechopen.com/books/pluripotent-stem-cells/molecular-mechanisms-underlying-pluripotency">Pluripotent Stem Cells</a>. https://doi.org/10.5772/55596</p> <p>Fernandez-Alonso, R., Bustos, F., Williams, C. A. C., & Findlay, G. M. (2017). <a href="https://www.sciencedirect.com/science/article/pii/S0022283617301894?via%3Dihub">Protein Kinases in Pluripotency—Beyond the Usual Suspects</a>. Journal of Molecular Biology. https://doi.org/10.1016/j.jmb.2017.04.013</p> <p>Katoh, M., & Katoh, M. (2007). <a href="https://clincancerres.aacrjournals.org/content/13/14/4042">WNT signaling pathway and stem cell signaling network</a>. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-06-2316</p> <p>Lanner, F., & Rossant, J. (2010). <a href="https://dev.biologists.org/content/137/20/3351">The role of FGF/</a><a href="https://dev.biologists.org/content/137/20/3351">Erk</a><a href="https://dev.biologists.org/content/137/20/3351"> signaling in pluripotent cells</a>. Development. https://doi.org/10.1242/dev.050146</p> <p>Lee, J., Park, Y. J., & Jung, H. (2019). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681599/">Protein Kinases and Their Inhibitors in Pluripotent Stem Cell Fate Regulation</a>. Stem Cells International. https://doi.org/10.1155/2019/1569740</p> <p>Mullen, A. C., & Wrana, J. L. (2017). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495062/">TGF-β family signaling in embryonic and somatic stem-cell renewal and differentiation</a>. Cold Spring Harbor Perspectives in Biology. https://doi.org/10.1101/cshperspect.a022186</p> <p>Takahashi, K., & Yamanaka, S. (2006). <a href="https://www.ncbi.nlm.nih.gov/pubmed/16904174">Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors</a>. Cell. https://doi.org/10.1016/j.cell.2006.07.024</p> <p>Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007). <a href="https://www.ncbi.nlm.nih.gov/pubmed/18035408">Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors</a>. Cell. https://doi.org/10.1016/j.cell.2007.11.019</p> <p>Tang, Y., & Tian, X. (Cindy). (2013). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894236/">JAK-STAT3 and somatic cell reprogramming</a>. JAK-STAT. https://doi.org/10.4161/jkst.24935</p> <p>Zakrzewski, W., Dobrzyński, M., Szymonowicz, M., & Rybak, Z. (2019). <a href="https://stemcellres.biomedcentral.com/articles/10.1186/s13287-019-1165-5">Stem cells: Past, present, and future. </a><a href="https://stemcellres.biomedcentral.com/articles/10.1186/s13287-019-1165-5">Stem Cell Research and Therapy</a>. https://doi.org/10.1186/s13287-019-1165-5</p> </td> </tr> </table> <map name="map1"> <area shape="RECT" coords="25,276,61,294" href="https://www.novusbio.com/common-name/klf4" title="klf4"/> <area shape="RECT" coords="27,300,73,317" href="https://www.novusbio.com/common-name/npm1" title="npm1"/> <area shape="RECT" coords="26,320,68,338" href="https://www.novusbio.com/common-name/rpa70" title="rpa70"/> <area shape="RECT" coords="25,342,67,358" href="https://www.novusbio.com/common-name/sall4" title="sall4"/> <area shape="RECT" coords="218,102,255,117" href="https://www.novusbio.com/common-name/tcf-3-e2a" title="tcf-3-e2a"/> <area shape="RECT" coords="219,79,264,95" href="https://www.novusbio.com/common-name/stat3" title="stat3"/> <area 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