The Polo group is interested in the transcriptional and epigenetic mechanisms that govern cell identity and cell fate. It has a particular focus on pluripotency and the reprogramming of somatic cells into induced pluripotent stem (iPS) cells and other mature cell types.

Being able to reprogram any specific mature cell into a pluripotent state and then back into any other particular cell gives the group a unique tool to study the molecular and cellular events that permit the conversion of one cell type to another.

Moreover, iPS cells and the reprogramming technology are of great interest in pharmaceutical and clinical settings, as the technology can be used to generate animal and cellular models for the study of various diseases as well as provide (in the future) specific patient tailor-made cells for their use in cellular replacement therapies.


The Polo group is dissecting the nature and dynamics of the process using a broad array of approaches through the use of mouse models and a combination of different molecular, biochemical and cellular techniques, and genome-wide studies.

Group Members

Research Themes

  • The kinetics and universality of the epigenetic and genomic changes occurring during reprogramming
  • The composition and assembly kinetics of transcriptional regulation complexes at pluripotency genes
  • How the cell of origin influences the in vitro and in vivo plasticity potential of cells generated during the reprogramming process
  • The epigenetics changes occurring in adult stem cells as a consequence of changes in their environment.

Featured Publications

Authors Title Published In

Knaupp AS, Buckberry S, Pflueger J, Lim SM, Ford E, Larcombe MR, Rossello FJ, de Mendoza A, Alaei S, Firas J, Holmes ML, Nair SS, Clark SJ, Nefzger CM, Lister R, Polo JM.

Transient and permanent reconfiguration of chromatin and transcription factor occupancy drive reprogramming.

Cell Stem Cell. 2017 Dec 7;21(6):834-845.e6. doi: 10.1016/j.stem.2017.11.007.

Nefzger CM, Rossello FJ, Chen J, Liu X, Knaupp AS, Firas J, Paynter JM, Pflueger J, Buckberry S, Lim SM, Williams B, Alaei S, Faye-Chauhan K, Petretto E, Nilsson SK, Lister R, Ramialison M, Powell DR, Rackham OJL, Polo JM.

Cell type of origin dictates the route to pluripotency.

Cell Rep. 2017 Dec 5;21(10):2649-2660. doi: 10.1016/j.celrep.2017.11.029.

Liu X, Nefzger CM, Rossello FJ, Chen J, Knaupp AS, Firas J, Ford E, Pfleuger J, Paynter JM, Chy HS, O’Brien CM, Huang C, Mishra K, Hodgson-Garms M, Jansz N, Williams SM, Blewitt ME, Nilsson SK, Schittenhelm RB, Laslett AL, Lister R, Polo JM.

Comprehensive characterization of distinct states of human naive pluripotency generated by reprogramming.

Nat Methods. 2017 Nov;14(11):1055-1062. doi: 10.1038/nmeth.4436. Epub 2017 Sep 25.

Rackham OJ, Firas J, Fang H, Oates ME, Holmes ML, Knaupp AS; FANTOM Consortium, Suzuki H, Nefzger CM, Daub CO, Shin JW, Petretto E, Forrest AR, Hayashizaki Y, Polo JM, Gough J.

A predictive computational framework for direct reprogramming between human cell types.

Nat Genet. 2016 Mar;48(3):331-5. doi: 10.1038/ng.3487. Epub 2016 Jan 18.

More Publications

Authors Title Published In

Lee JY, Kim MJ, Deliyanti D, Azari MF, Rossello F, Costin A, Ramm G, Stanley EG, Elefanty AG, Wilkinson-Berka JL, Petratos S.

Overcoming monocarboxylate transporter 8 (MCT8)-deficiency to promote human oligodendrocyte differentiation and myelination.

EBioMedicine. 2017 Nov;25:122-135. doi: 10.1016/j.ebiom.2017.10.016. Epub 2017 Oct 19.

Firas J, Polo JM.

Towards understanding transcriptional networks in cellular reprogramming.

Curr Opin Genet Dev. 2017 Oct;46:1-8. doi: 10.1016/j.gde.2017.06.001. Epub 2017 Jun 21.

Nguyen PD, Gurevich DB, Sonntag C, Hersey L, Alaei S, Nim HT, Siegel A, Hall TE, Rossello FJ, Boyd SE, Polo JM, Currie PD.

Muscle stem cells undergo extensive clonal drift during tissue growth via Meox1-Mediated induction of G2 cell-cycle arrest.

Cell Stem Cell. 2017 Jul 6;21(1):107-119.e6. doi: 10.1016/j.stem.2017.06.003.

Mariño E, Richards JL, McLeod KH, Stanley D, Yap YA, Knight J, McKenzie C, Kranich J, Oliveira AC, Rossello FJ, Krishnamurthy B, Nefzger CM, Macia L, Thorburn A, Baxter AG, Morahan G, Wong LH, Polo JM, Moore RJ, Lockett TJ, Clarke JM, Topping DL, Harrison LC, Mackay CR.

Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes.


Nat Immunol. 2017 May;18(5):552-562. doi: 10.1038/ni.3713. Epub 2017 Mar 27.

Nefzger CM, Polo JM.

DEAD-Box RNA binding protein DDX5: Not a black-box during reprogramming.

Cell Stem Cell. 2017 Apr 6;20(4):419-420. doi: 10.1016/j.stem.2017.03.006.

Liu X, Chen J, Firas J, Paynter JM, Nefzger CM, Polo JM.

Generation of mouse induced pluripotent stem cells by lentiviral transduction.

Methods Mol Biol. 2019;1940:63-76. doi: 10.1007/978-1-4939-9086-3_5.

Kamaraj US, Gough J, Polo JM, Petretto E, Rackham OJ.

Computational methods for direct cell conversion.


Cell Cycle. 2016 Dec 16;15(24):3343-3354. doi: 10.1080/15384101.2016.1238119. Epub 2016 Oct 13.

Alaei S, Knaupp AS, Lim SM, Chen J, Holmes ML, Änkö ML, Nefzger CM, Polo JM.

An improved reprogrammable mouse model harbouring the reverse tetracycline-controlled transcriptional transactivator 3.

Stem Cell Res. 2016 Jul;17(1):49-53. doi: 10.1016/j.scr.2016.05.008. Epub 2016 May 25.

Nefzger CM, Jardé T, Rossello FJ, Horvay K, Knaupp AS, Powell DR, Chen J, Abud HE, Polo JM.

A versatile strategy for isolating a highly enriched population of inteistinal stem cells. 


Stem Cell Reports. 2016 Feb 18. doi: 10.1016/j.stemcr.2016.01.014. 2016 Feb 25.

Horvay K, Jardé T, Casagranda F, Perreau VM, Haigh K, Nefzger CM, Akhtar R, Gridley T, Berx G, Haigh JJ, Barker N, Polo JM, Hime GR, Abud HE.

Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium.


EMBO J. 2015 May 12;34(10):1319-35. doi: 10.15252/embj.201490881. Epub 2015 Mar 10.

Firas J, Liu X, Lim SM, Polo JM.

Transcription factor-mediated reprogramming: epigenetics and therapeutic potential.


Immunol Cell Biol. 2015 Mar;93(3):284-9. doi: 10.1038/icb.2015.5. Epub 2015 Feb 3.

Shu R, Wong W, Ma QH, Yang ZZ, Zhu H, Liu FJ, Wang P, Ma J, Yan S, Polo JM, Bernard CC, Stanton LW, Dawe GS, Xiao ZC.

APP intracellular domain acts as a transcriptional regulator of miR-663 suppressing neuronal differentiation.

Cell Death Dis. 2015 Feb 19;6:e1651. doi: 10.1038/cddis.2015.10.

Nefzger CM, Alaei S, Polo JM.

Isolation of reprogramming intermediates during generation of induced pluripotent stem cells from mouse embryonic fibroblasts.


Methods Mol Biol. 2015;1330:205-18. doi: 10.1007/978-1-4939-2848-4_17.

Nefzger CM, Alaei S, Knaupp AS, Holmes ML, Polo JM.

Cell surface marker mediated purification of iPS cell intermediates from a reprogrammable mouse model.


J Vis Exp. 2014 Sep 6;(91):e51728. doi: 10.3791/51728.

Firas J, Liu X, Polo JM.

Epigenetic memory in somatic cell nuclear transfer and induced pluripotency: Evidence and implications.


Differentiation. 2014 Jul;88(1):29-32. doi: 10.1016/j.diff.2014.09.001. Epub 2014 Oct 1.

Firas J, Liu X, Nefzger CM, Polo JM.

GM-CSF and MEF-conditioned media support feeder-free reprogramming of mouse granulocytes to iPS cells.


Differentiation. 2014 Jun;87(5):193-9. doi: 10.1016/j.diff.2014.05.003. Epub 2014 Jul 8.

David L, Polo JM.

Phases of reprogramming.


Stem Cell Res. 2014 May;12(3):754-61. doi: 10.1016/j.scr.2014.03.007. Epub 2014 Apr 1.

Nefzger CM, Alaei S, Polo JM.

Isolation of reprogramming intermediates during generation of induced pluripotent stem cells from mouse embryonic fibroblasts.


Methods Mol Biol. 2015;1330:205-18. doi: 10.1007/978-1-4939-2848-4_17.

Hobbs RM and Polo JM.

Reprogramming can be a transforming experience.


Cell Stem Cell. 2014 Mar 6;14(3):269-71. doi: 10.1016/j.stem.2014.02.003.

Hatzi K, Jiang Y, Huang C, Garrett-Bakelman F, Gearhart MD, Giannopoulou EG, Zumbo P, Kirouac K, Bhaskara S, Polo JM, Kormaksson M, MacKerell AD Jr, Xue F, Mason CE, Hiebert SW, Prive GG, Cerchietti L, Bardwell VJ, Elemento O, Melnick A.

A hybrid mechanism of action for BCL6 in B-cells defined by formation of functionally distinct complexes at enhancers and promoters.


Cell Rep. 2013 Aug 15;4(3):578-88. doi: 10.1016/j.celrep.2013.06.016. Epub 2013 Aug 1.

Apostolou E, Ferrari F, Walsh RM, Bar-Nur O, Stadtfeld M, Cheloufi S, Stuart HT, Polo JM, Ohsumi TK, Borowsky ML, Kharchenko PV, Park PJ, Hochedlinger K.

Genome-wide chromatin interactions of the Nanog locus in pluripotency, differentiation, and reprogramming.


Cell Stem Cell. 2013 Jun 6;12(6):699-712. doi: 10.1016/j.stem.2013.04.013. Epub 2013 May 9.

De S, Shaknovich R, Riester M, Elemento O, Geng H, Kormaksson M, Jiang Y, Woolcock B, Johnson N, Polo JM, Cerchietti L, Gascoyne RD, Melnick A, Michor F.

Aberration in DNA methylation in B-cell lymphomas has a complex origin and increases with disease severity.


PLoS Genet. 2013;9(1):e1003137. doi: 10.1371/journal.pgen.1003137. Epub 2013 Jan 10.

Kelly RD, Rodda AE, Dickinson A, Mahmud A, Nefzger CM, Lee W, Forsythe JS, Polo JM, Trounce IA, McKenzie M, Nisbet DR, St John JC.

Mitopchondrial DNA haplotypes define gene expression patterns in pluripotent and differentiating embryonic stem cells.


Stem Cells. 2013 Apr;31(4):703-16. doi: 10.1002/stem.1313.

Polo JM, Anderssen E, Walsh RM, Schwarz BA, Nefzger CM, Lim SM, Borkent M, Apostolou E, Alaei S, Cloutier J, Bar-Nur O, Cheloufi S, Stadtfeld M, Figueroa ME, Robinton D, Natesan S, Melnick A, Zhu J, Ramaswamy S, Hochedlinger K.

A molecular roadmap of reprogramming somatic cells into iPS cells.


Cell. 2012 Dec 21;151(7):1617-32. doi: 10.1016/j.cell.2012.11.039.

Arnold K, Sarkar A, Yram MA, Polo JM, Bronson R, Sengupta S, Seandel M, Geijsen N, Hochedlinger K.

Sox2(+) adult stem and progenitor cells are important for tissue regeneration and survival of mice.


Cell Stem Cell. 2011 Oct 4;9(4):317-29. doi: 10.1016/j.stem.2011.09.001.

Ohi Y, Qin H, Hong C, Blouin L, Polo JM, Guo T, Qi Z, Downey SL, Manos PD, Rossi DJ, Yu J, Hebrok M, Hochedlinger K, Costello JF, Song JS, Ramalho-Santos M.

Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells


Nat Cell Biol. 2011 May;13(5):541-9. doi: 10.1038/ncb2239. Epub 2011 Apr 17.

Polo JM, Liu S, Figueroa ME, Kulalert W, Eminli S, Tan KY, Apostolou E, Stadtfeld M, Li Y, Shioda T, Natesan S, Wagers AJ, Melnick A, Evans T, Hochedlinger K.

Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells.

Nat Biotechnol 2010 Jul 09;28:848-855. doi: 10.1038/nbt.1667. Epub 2010 Jul 19.

Polo JM, Hochedlinger K.

When fibroblasts MET iPSCs


Cell Stem Cell. 2010 Jul 2;7(1):5-6. doi: 10.1016/j.stem.2010.05.018. Epub 2010 Jun 17.

Buecker C, Chen HH, Polo JM, Daheron L, Bu L, Barakat TS, Okwieka P, Porter A, Gribnau J, Hochedlinger K, Geijsen N.

A murine ESC-like state facilitates transgenesis and homologous recombination in human pluripotent stem cells.

Cell Stem Cell. 2010 Jun 4;6(6):535-46. doi: 10.1016/j.stem.2010.05.003.

Utikal J, Polo JM, Stadtfeld M, Maherali N, Kulalert W, Walsh RM, Khalil A, Rheinwald JG, Hochedlinger K.

Immortalization eliminates a roadblock during cellular reprogramming into iPS cells.


Nature. 2009 Aug 27;460(7259):1145-8. doi: 10.1038/nature08285. Epub 2009 Aug 9.

Polo JM, Ci W, Licht JD, Melnick A.

Reversible disruption of BCL6 repression complexes by CD40 signaling in normal and malignant B cells.

Blood. 2008 Aug 1;112(3):644-51. doi: 10.1182/blood-2008-01-131813. Epub 2008 May 16.

Ranuncolo SM, Polo JM, Dierov J, Singer M, , Kuo T, Greally J, Green R, Carroll M and Melnick A.

BCL6 mediates the germinal center B-cell phenotype and lymphomagenesis through transcriptional repression of ATR.


Nat Immunol. 2007 Jul;8(7):705-14. doi: 10.1038/ni1478. Epub 2007 Jun 10.

Polo JM, Dell’Oso T, Ranuncolo SM, Cerchietti L, Beck D, Da Silva GF, Prive GG, Licht JD, Melnick A.

Specific peptide interference reveals BCL-6 transcriptional and oncogenic mechanisms in B-cell lymphoma cells.

Nat Med. 2004 Dec;10(12):1329-35. doi: 10.1038/nm1134. Epub 2004 Nov 7.