Our group reported the first derivation of embryonic stem (ES) cells from a non-human primate in 1995, work that led us to the first derivation of human ES cells in 1998. Human ES cells are capable of unlimited undifferentiated proliferation, and yet maintain the ability to form all the cells of the body. Much of our early work focused on developing the basic tools (for example, transfection techniques, homologous recombination, and culture conditions) needed to establish human ES cells as a useful experimental model. My group has also been involved in demonstrating the developmental potential of human ES cells in lineage-specific differentiation (such as blood, trophoblast, neural tissue, and heart). Ultimately, the differentiated derivatives of human ES cells could have important applications in transplantation medicine, and we continue some studies of lineage-specific differentiation in collaboration with UW physician scientists.

The current focus of my lab is on understanding the ES cell itself. We wish to understand why this cell can form any cell in the body (pluripotency); how an ES cell chooses between self-renewal and the initial decision to differentiate; what determines which developmental transitions are allowed or not-allowed; and how a differentiated cell with limited developmental potential can be reprogrammed to a pluripotent cell.

Recent Publications

Yu J, Hu K, Smuga-Otto K, Tian S, Stewart R, Slukvin II, Thomson JA. "Human induced pluripotent stem cells free of vector and transgene sequences." Science. 2009 Mar 26. [Epub ahead of print]

Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo LQ, Edsall LE, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR. "Human DNA methylomes at base resolution show widespread epigenomic differences." Nature. Published online Oct 14 2009.[PubMed]

Xu N, Papagiannakopoulos T, Pan G, Thomson JA, Kosik K. "MicroRNA-145 Regulates OCT4, SOX2, and KLF4 and Represses Pluripotency in Human Embryonic Stem Cells." Cell. 2009 May 15:137(4):647-58. [PubMed]

Heintzman ND, Hon GC, Hawkins RD, Kheradpour P, Stark A, Harp LF, Ye Z, Lee LK, Stuart RK, Ching CW, Ching KA, Antosiewicz-Bourget JE, Liu H, Zhang X, Green RD, Lobanenkov VV, Stewart R, Thomson JA, Crawford GE, Kellis M, Ren B. "Histone Modifications at Human Enhancers Reflect Global Cell-Type-Specific Gene Expression." Nature. 2009 May 7;459:108-112. [PubMed]

Swaney DL, Wenger CD, Thomson JA, Coon JJ. "Human Embryonic Stem Cell Phosphoproteome Revealed by Electron Transfer Dissociation Tandem Mass Spectrometry." Proc Natl Acad Sci USA. 2009 January 27;106(4):995-1000. PMCID: PMC2633571 [PubMed]

Ebert AD, Yu J, Rose FF Jr, Mattis VB, Lorson CL, Thomson JA, Svendsen CN. "Induced pluripotent stem cells from a spinal muscular atrophy patient." Nature. 2009 Jan 15;457(7227):277-80. [PubMed]

Xu RH, Sampsell-Barron TL, Gu F, Root S, Peck RM, Pan G, Yu J, Antosiewicz-Bourget J, Tian S, Stewart R, Thomson JA. "NANOG is a direct target of TGFbeta/activin-mediated SMAD signaling in human ESCs." Cell Stem Cell. 2008 Aug 7;3(2):196-206. [PubMed]

Yu J, Thomson JA. "Pluripotent stem cell lines." Genes Dev. 2008 Aug 1;22(15):1987-97. Review. [PubMed]

Dejosez M, Krumenacker JS, Zitur LJ, Passeri M, Chu LF, Songyang Z, Thomson JA, Zwaka TP. "Ronin is essential for embryogenesis and the pluripotency of mouse embryonic stem cells." Cell. 2008 Jun 27;133(7):1162-74. Erratum in: Cell. 2008 Aug 22;134(4):692. [PubMed]

Fujita J, Crane AM, Souza MK, Dejosez M, Kyba M, Flavell RA, Thomson JA, Zwaka TP. "Caspase activity mediates the differentiation of embryonic stem cells." Cell Stem Cell. 2008 Jun 5;2(6):595-601. [PubMed]

Phanstiel D, Brumbaugh J, Berggren WT, Conard K, Feng X, Levenstein ME, McAlister GC, Thomson JA, Coon JJ. "Mass spectrometry identifies and quantifies 74 unique histone H4 isoforms in differentiating human embryonic stem cells." Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4093-8. [PubMed]

Yu J, Vodyanik M, Smuga-Otto K, Frane J, Antosiewicz-Bourget J, Frane J, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA."Induced pluripotent stem cell lines derived from human somatic cells." Science. 318 (2007):1917-1920. [Science Abstract] [Science Complete Article] [PubMed]

Pan G, Tian S, Nie J, Yang C, Ruotti V, Wei H, Jonsdottir GA, Stewart R, Thomson JA. "Whole-genome analysis of histone H3 lysine 4 and lysine 27 methylation in human embryonic stem cells." Cell Stem Cell. 2007 Sep 13;1(3):299-312. [PubMed]

Yu J, Vodyanik MA, He P, Slukvin II, Thomson JA. "Human embryonic stem cells reprogram myeloid precursors following cell-cell fusion." Stem Cells. 2006 Jan;24(1):168-76. [PubMed]

Ludwig TE, Bergendahl V, Levenstein ME, Yu J, Probasco MD, Thomson JA. "Feeder-independent culture of human embryonic stem cells." Nat Methods. 2006 Aug;3(8):637-646. [PubMed]

Ludwig TE, Levenstein ME, Jones J, Berggren W, Mitchen E, Frane J, Crandall L, Daigh CA, Conard K, Piekarczyk M, Llanas R, Thomson JA. "Derivation of human embryonic stem cells in defined conditions." Nat Biotechnol. 2006 Feb;24(2):185-7. [PubMed]

Xu RH, Peck RM, Li DS, Feng X, Ludwig T, Thomson JA. "Basic FGF and suppression of BMP signaling sustain undifferentiated proliferation of human ES cells." Nat Methods. 2005 Mar;2(3):185-90. [PubMed]

Zwaka TP, Thomson JA. "A germ cell origin of embryonic stem cells?" Development. 2005 Jan;132(2):227-33. [PubMed]

Draper, J.S., K. Smith, P. Gokhale, H. D. Moore, E. Maltby, J. Johnson, L. Meisner, T. P. Zwaka, J. A. Thomson and P.W.Andrews."Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells" Nat Biotechnol. 22 (2004):53-54. [PubMed]

Sperger, J.M, X. Chen, J.S. Draper, J.E. Antosiewicz, C. Chon, S. Jones, J.D. Brooks, P.W. Andrews, P.O. Brown, and J.A. Thomson. "Gene expression patterns in human embryonic stem cells and human pluripotent germ cell tumors" Proc Natl Acad Sci USA. 100 (2003):13350-13355. [PubMed]

Zwaka, T.P and J.A. Thomson. "Homologous recombination in human embryonic stem cells" Nat Biotechnol. 21 (2003):319-21. [PubMed]

Xu, R., X. Chen, D.S. Li, R. Li, G.C. Addicks, C. Glennon, T.P. Zwaka, and J.A. Thomson. "BMP4 initiates human embryonic stem cell differentiation to trophoblast" Nat Biotechnol. 20 (2002):1261-1264. [PubMed]

Zhang, S-C., M. Wernig, I.D. Duncan, O. Brustle, and J.A. Thomson. "In vitro differentiation and transplantation of human ES cell-derived neural precursors." Nat Biotechnol. 19 (2001):1129-1133. [PubMed]

Kaufman, D.S., E.T. Hanson, R.L. Lewis, R. Auerbach, and J.A. Thomson. "Hematopoietic colony forming cells derived from human embryonic stem cells" Proc Natl Acad Sci USA. 98 (2001):10716-10721. [PubMed]

Amit, M., M. Carpenter, M. Inokuma, C. Chiu, C.P. Harris, M.A. Waknitz, J. Itskovitz-Eldor, and J.A. Thomson. "Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture" Dev Biol. 227, 2 (2000):271-278. [PubMed]

Thomson, J.A., J. Itskovitz-Eldor, S.S. Shapiro, M.A. Waknitz, J.J. Swiergiel, V.S. Marshall, and J.M. Jones. "Embryonic stem cell lines derived from human blastocysts" Science 282 (1998):1145-1147. [PubMed]

Thomson, J.A. and V.S. Marshall. "Primate embryonic stem cells" Curr. Top. in Dev. Biol. 38 (1998):133-160. [PubMed]

Thomson, J.A., R. Becker, M. Durning, T.G. Golos, C. Harris, J. Kalishman, and J.P. Hearn. "Isolation of a primate embryonic stem cell line" Proc Natl Acad Sci USA. 92 (1995):7844-7848. [PubMed]