JAK/STAT3 Signalling is Sufficient and Dominant over Antagonistic Cues for the Establishment of Naive Pluripotency

Overview

Journal Nat Commun

Specialty Biology

Date 2012 May 10

PMID 22569365

Citations 57

Authors

Anouk L van Oosten

Yael Costa

Austin Smith

Jose C R Silva

Affiliations

Soon will be listed here.

Abstract

Induced pluripotency depends on cooperativity between expression of defined factors and the culture environment. The latter also determines the pluripotent cell state, that is, naïve or primed. LIF-JAK/STAT3 signalling was recently shown to be a limiting factor for reprogramming to naïve pluripotency. Here we show that sufficient activation of JAK/STAT3 overcomes the reprogramming block of cell intermediates and enables somatic cell reprogramming in absence of otherwise essential pluripotency medium requisites. Activation of FGF-ERK signalling, which promotes exit of naïve pluripotent cells from self-renewal, does not prevent JAK/STAT3 induced post-implantation epiblast-derived stem cell conversion into naïve pluripotency. Moreover, even in the presence of FGF plus Activin, which instructs and maintains the primed state, JAK/STAT3 enforces naïve pluripotency in epiblast stem cells. We conclude that JAK/STAT3 signalling can be sufficient and dominant over antagonistic cues to enable the induction of a naïve pluripotent state.

Citing Articles

Interplay of chromatin remodeling BAF complexes in mouse embryonic and epiblast stem cell conversion and maintenance.

Ma Z, Tan S, Lu R, Chen P, Hu Y, Yang T J Biol Chem. 2024; 301(2):108140.

PMID: 39730061 PMC: 11791114. DOI: 10.1016/j.jbc.2024.108140.

Elucidation of the pluripotent potential of bovine embryonic lineages facilitates the establishment of formative stem cell lines.

Zhi M, Gao D, Yao Y, Zhao Z, Wang Y, He P Cell Mol Life Sci. 2024; 81(1):427.

PMID: 39377807 PMC: 11461730. DOI: 10.1007/s00018-024-05457-z.

The interferon γ pathway enhances pluripotency and X-chromosome reactivation in iPSC reprogramming.

Barrero M, Lazarenkov A, Blanco E, Palma L, Lopez-Rubio A, Bauer M Sci Adv. 2024; 10(32):eadj8862.

PMID: 39110794 PMC: 11305397. DOI: 10.1126/sciadv.adj8862.

Crosstalk between Signaling Pathways and Energy Metabolism in Pluripotency.

Kim K, Kim S, Cha H Int J Stem Cells. 2024; 18(1):12-20.

PMID: 38494425 PMC: 11867904. DOI: 10.15283/ijsc23173.

Molecular docking analysis of the oral tumor target JAK STAT 3 with oxo-azo compounds.

Karikalan K, Veeraraghavan V, Sekaran S, Rengasamy G, Sankaran K, Eswaramoorthy R Bioinformation. 2023; 19(1):63-68.

PMID: 37720284 PMC: 10504500. DOI: 10.6026/97320630019063.

References

Brons I, Smithers L, Trotter M, Rugg-Gunn P, Sun B, Chuva de Sousa Lopes S . Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature. 2007; 448(7150):191-5. DOI: 10.1038/nature05950. View

Jiang J, Chan Y, Loh Y, Cai J, Tong G, Lim C . A core Klf circuitry regulates self-renewal of embryonic stem cells. Nat Cell Biol. 2008; 10(3):353-60. DOI: 10.1038/ncb1698. View

Kawamura T, Suzuki J, Wang Y, Menendez S, Morera L, Raya A . Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature. 2009; 460(7259):1140-4. PMC: 2735889. DOI: 10.1038/nature08311. View

Bourillot P, Aksoy I, Schreiber V, Wianny F, Schulz H, Hummel O . Novel STAT3 target genes exert distinct roles in the inhibition of mesoderm and endoderm differentiation in cooperation with Nanog. Stem Cells. 2009; 27(8):1760-71. DOI: 10.1002/stem.110. View

Yoshiura S, Ohtsuka T, Takenaka Y, Nagahara H, Yoshikawa K, Kageyama R . Ultradian oscillations of Stat, Smad, and Hes1 expression in response to serum. Proc Natl Acad Sci U S A. 2007; 104(27):11292-7. PMC: 1899192. DOI: 10.1073/pnas.0701837104. View

Tesar P, Chenoweth J, Brook F, Davies T, Evans E, Mack D . New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature. 2007; 448(7150):196-9. DOI: 10.1038/nature05972. View

Silva J, Smith A . Capturing pluripotency. Cell. 2008; 132(4):532-6. PMC: 2427053. DOI: 10.1016/j.cell.2008.02.006. View

Kunath T, Saba-El-Leil M, Almousailleakh M, Wray J, Meloche S, Smith A . FGF stimulation of the Erk1/2 signalling cascade triggers transition of pluripotent embryonic stem cells from self-renewal to lineage commitment. Development. 2007; 134(16):2895-902. DOI: 10.1242/dev.02880. View

Bao S, Tang F, Li X, Hayashi K, Gillich A, Lao K . Epigenetic reversion of post-implantation epiblast to pluripotent embryonic stem cells. Nature. 2009; 461(7268):1292-5. PMC: 3863718. DOI: 10.1038/nature08534. View

10.

Yang J, van Oosten A, Theunissen T, Guo G, Silva J, Smith A . Stat3 activation is limiting for reprogramming to ground state pluripotency. Cell Stem Cell. 2010; 7(3):319-28. PMC: 3459098. DOI: 10.1016/j.stem.2010.06.022. View

11.

Silva J, Barrandon O, Nichols J, Kawaguchi J, Theunissen T, Smith A . Promotion of reprogramming to ground state pluripotency by signal inhibition. PLoS Biol. 2008; 6(10):e253. PMC: 2570424. DOI: 10.1371/journal.pbio.0060253. View

12.

Chambers I, Silva J, Colby D, Nichols J, Nijmeijer B, Robertson M . Nanog safeguards pluripotency and mediates germline development. Nature. 2007; 450(7173):1230-4. DOI: 10.1038/nature06403. View

13.

Du P, Kibbe W, Lin S . lumi: a pipeline for processing Illumina microarray. Bioinformatics. 2008; 24(13):1547-8. DOI: 10.1093/bioinformatics/btn224. View

14.

Silva J, Chambers I, Pollard S, Smith A . Nanog promotes transfer of pluripotency after cell fusion. Nature. 2006; 441(7096):997-1001. DOI: 10.1038/nature04914. View

15.

Hall J, Guo G, Wray J, Eyres I, Nichols J, Grotewold L . Oct4 and LIF/Stat3 additively induce Krüppel factors to sustain embryonic stem cell self-renewal. Cell Stem Cell. 2009; 5(6):597-609. DOI: 10.1016/j.stem.2009.11.003. View

16.

Greber B, Wu G, Bernemann C, Joo J, Han D, Ko K . Conserved and divergent roles of FGF signaling in mouse epiblast stem cells and human embryonic stem cells. Cell Stem Cell. 2010; 6(3):215-26. DOI: 10.1016/j.stem.2010.01.003. View

17.

Stavridis M, Lunn J, Collins B, Storey K . A discrete period of FGF-induced Erk1/2 signalling is required for vertebrate neural specification. Development. 2007; 134(16):2889-94. DOI: 10.1242/dev.02858. View

18.

Niwa H, Ogawa K, Shimosato D, Adachi K . A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells. Nature. 2009; 460(7251):118-22. DOI: 10.1038/nature08113. View

19.

Takahashi K, Yamanaka S . Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4):663-76. DOI: 10.1016/j.cell.2006.07.024. View

20.

Theunissen T, van Oosten A, Castelo-Branco G, Hall J, Smith A, Silva J . Nanog overcomes reprogramming barriers and induces pluripotency in minimal conditions. Curr Biol. 2011; 21(1):65-71. PMC: 3025321. DOI: 10.1016/j.cub.2010.11.074. View