TABLE 1.
Selected factors that influence the interconversions of mESCs and EpiSCs.
| Molecule(s) | Function | Effect on mESCs, EpiSCs, and their interconversion | References |
| Brd9/BAF complex | Chromatin remodeler | BRD9, through a non-canonical BAF complex, blocks transition to a primed state | Gatchalian et al., 2018 |
| Epiblastin A | Inhibitor | Inhibits CK1 and induces EpiSC-to-mESC conversion | Illich et al., 2016 |
| Esrrb | Transcription factor | Overexpression sustains LIF-independent self-renewal in the absence of Nanog and reverts EpiSCs to mESCs | Festuccia et al., 2012; Adachi et al., 2018 |
| Hif1a | Transcription factor | HIF-1α activation switches mESC metabolism and pushes cells toward an EpiSC-like state | Zhou et al., 2012 |
| iPStat3 | Gp130Y118F receptor | Artificially induces STAT3 signaling and converts mESCs to EpiSCs | Stuart et al., 2019 |
| Kdm1a/Kmt2d (MLL4) | Histone methylation | Kmt2d (MLL4) is required to exit pluripotency; knockdown of Kdm1a restores the ability of mESCs to convert to EpiSCs | Cao et al., 2018 |
| Kdm6b (JMJD3) | Histone demethylase | Demethylates H3K27me2 or H3K27me3; Kdm6b facilitates a Klf4-driven EpiSC-to-ESC conversion | Huang et al., 2020 |
| Klf2, Klf4 | Transcription factor | Overexpression sustains LIF-independent self-renewal and can convert EpiSCs to mESCs | Guo et al., 2009 |
| Kmt2a (MLL1) | Epigenetic inhibitor | H3K4me1 methyltransferase, deletion of Kmt2a (MLL1) impairs mESC differentiation to EpiLCs; MLL1 Inhibition reprograms EpiSCs to mESCs | Zhang et al., 2016 |
| Nanog | Transcription factor | Transient transfection of Nanog mediates reprogramming of mESCs to EpiSCs | Silva et al., 2009 |
| Nr5a1, Nr5a2 | Transcription factor | Overexpression reprograms EpiSCs to mESCs | Guo and Smith, 2010 |
| Otx2 | Transcription factor | Required to stably establish EpiSCs | Acampora et al., 2013 |
| Prdm14 | Epigenetic factor | Overexpression drives EpiLCs to mESC-like cells | Okashita et al., 2016 |
| Sall1 | Transcription factor | Promotes reprogramming EpiSCs to mESCs | Yang et al., 2019a |
| Setdb1 | Histone methyltransferase | Methyltransferase for H3K9me3; Setdb1 loss enriches a transient 2C-like state in mESCs | Wu et al., 2020 |
| Smarcad1 | SWI/SNF helicase | Knockdown converts mESCs to EpiSC-like cells | Xiao et al., 2017 |
| Tcf3, Etv5, Rbpj | Transcription factors | mESCs lacking Tcf3, Etv5, and Rbpj are trapped in a naïve pluripotent condition and are difficult to differentiate | Kalkan et al., 2019 |
| Tfe3 | Transcription factor | Nuclear-localized TFE3 blocks mESCs from differentiating | Betschinger et al., 2013 |
| Wnt, Gsk3b | Transcription factor | Wnt signaling blocks the conversion of mESCs to EpiSCs and maintains mESCs in the naïve state | Ying et al., 2008; ten Berge et al., 2011 |
| Zbtb7a/b | Transcription factor | Knockdown converts EpiSCs to naïve mESCs | Yu et al., 2020b |
| Zfp281 | Transcription factor | Deletion of Zfp281 promotes EpiSCs reprogramming and acts downstream of Ehmt1 (G9a-like protein; a histone methyltransferase for H3K9me1/2) | Mayer et al., 2020 |
| Zfp706 | Transcription factor | Deletion of Zfp706 promotes mESC self-renewal and promotes EpiSC reprogramming | Leeb et al., 2014 |
mESC, mouse embryonic stem cell; EpiSC, epiblast stem cell; LIF, leukemia inhibitory factor; EpiLC, epiblast-like cell.