The Polo laboratory is interested in the transcriptional and epigenetic mechanisms that govern cell identity, in particular pluripotency and the reprogramming of somatic cells into induced pluripotent stem (iPS) cells.

Being able to reprogram any specific mature cellular program into a pluripotent state and from there back into any other particular cellular program provides a unique tool to dissect 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, since the technology can be use to generate animal and cellular models for the study of various diseases as well in the future to provide specific patient tailor made cells for their use in cellular replacement therapies. However, despite being one of the major growing research fields very little is known about the epigenetic and transcriptome changes occurring during this process. 

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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.

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 in Molecular Biology 2017 (in press).

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.

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. [Epub ahead of print]

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, 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.

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.

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.

Kaur G, Costa MW, Nefzger CM, Silva J, Polo JM, Bell TDM, Plachta N.

Quantifying transcription factor diffusion in the living mammalian embryo by photoactivatable FCS.

Nat Comm 2013. doi: 10.1038/ncomms2657

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 J, Polo JM, Trounce IA, McKenzie M, Nisbet DR, St John JC.

Mitochondrial 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.

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 Aug;28(8):848-55. doi: 10.1038/nbt.1667. Epub 2010 Jul 19.

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.

Duy C, Yu JJ, Nahar R, Swaminathan S, Kweon SM, Polo JM, Valls E, Klemm L, Shojaee S, Cerchietti L, Schuh W, Jäck HM, Hurtz C, Ramezani-Rad P, Herzog S, Jumaa H, Koeffler HP, de Alborán IM, Melnick AM, Ye BH, Müschen M.

BCL6 is critical for the development of a diverse primary B cell repertoire

J Exp Med. 2010 Jun 7;207(6):1209-21. doi: 10.1084/jem.20091299. Epub 2010 May 24.

Utikal J and Polo JM*, Stadtfeld M, Maherali N, Kulalert W, Walsh RM, Khalil A, Rheinwald JG, Hochedlinger K. (*:Co- First Author).

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.

 

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