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Proteome Biology of Stem Cells

Stem cell biology is one of the most active fields of biological research today, because of the unique properties of stem cells to give rise to all cells of the adult body. This has moved to center stage even further after the introduction of methods to generate induced pluripotent stem cells (iPS) from somatic cells, providing a great tool to study fundamental aspects of pluripotency and differentiation. Furthermore, control of these properties in vitro would offer tremendous potential to develop treatments of diseases that cannot be cured today, especially in the area of regenerative medicine. However, since our understanding of most of the basic cellular process underlying stem cell self-renewal, maintenance and differentiation are still very limited it will be essential to expand our knowledge especially on the protein level if stem cells are to reach their full potential. This initiative aims to provide a platform for researchers from both stem cell and proteomic communities to define pressing issues in stem cell biology requiring proteomic analysis and to initiate collaborative projects. This initiative has been established jointly by HUPO and the International Society for Stem Cell Research (ISSCR) and is represented by leading scientists from both fields.

Current lines of work:

  • Characterization and comparison of proteome composition of various types of stem cells (embryonic, somatic, iPS)
  • Identification of stem cell-specific proteins and characterizing their role in stem cell behaviour (e.g. maintenance of pluripotency, differentiation)
  • Characterize the dynamic processes, at a proteome-wide scale, that underlie differentiation and reprogramming
  • Integration of proteomics and other omics data for a systems understanding of stem cell regulation
  • Characterization of post-translational modifications (PTMs) and changes in PTM profiles that accompany differentiation and reprogramming
  • Contribute data to public repositories to define cell type and organ-specific protein expression


A.D. Whetton, A.J. Williamson, J. Krijgsveld, B.H. Lee, I. Lemischka, S. Oh, M. Pera, C.L. Mummery , A.J. Heck. The time is right: proteome biology of stem cells (2008) Cell Stem Cell 2(3):215-7.

J. Krijgsveld, A.D. Whetton, B. Lee, I. Lemischka,.S. Oh, M. Pera, C. Mummery, and A.J.R. Heck. Proteome biology of stem cells, a new joint HUPO and ISSCR initiative (2008) Mol. Cell. Proteomics 7(1): 204-5.

D. van Hoof, A.J. R. Heck, J. Krijgsveld, and C.L. Mummery. Proteomics and human embryonic stem cells (2008) Stem Cell Research 1(3):169-182

Lu R, Markowetz F, Unwin RD, Leek JT, Airoldi EM, MacArthur BD, Lachmann A, Rozov R, Ma'ayan A, Boyer LA, Troyanskaya OG, Whetton AD, Lemischka IR. Systems-level dynamic analyses of fate change in murine embryonic stem cells (2009). Nature. 462(7271):358-62

D. Van Hoof, J. Muñoz, S.R. Braam, M.W.H. Pinkse, R. Linding, A.J.R. Heck, C.L. Mummery, and J. Krijgsveld. Phosphorylation dynamics during early differentiation of human embryonic stem cells (2009). Cell Stem Cell 5(2): 214-226

Dobbin E, Graham C, Freeburn RW, Unwin RD, Griffiths JR, Pierce A, Whetton AD, Wheadon H. Proteomic analysis reveals a novel mechanism induced by the leukemic oncogene Tel/PDGFRβ in stem cells: activation of the interferon response pathways (2010). Stem Cell Res.5(3):226-43.

Munoz J, Low TY, Kok YJ, Chin A, Frese CK, Ding V, Choo A, Heck AJ. The quantitative proteomes of human-induced pluripotent stem cells and embryonic stem cells (2011). Mol Syst Biol. 7:550.

Van Hoof D, Krijgsveld J, Mummery C. Proteomic analysis of stem cell differentiation and early development (2012). Cold Spring Harb Perspect Biol. 4(3) pii: a008177 (doi: 10.1101/cshperspect.a008177)

Klimmeck D., Hansson J., Raffel S., Vakhrushev S., Trumpp A. and Krijgsveld J. (2012). Proteomic cornerstones of multipotent hematopoietic stem and progenitor cells. Mol Cell Proteomics 11(8):286-302

Hansson J, Rafiee MR, Reiland S, Polo JM, Gehring J, Okawa S, Huber W, Hochedlinger K, Krijgsveld J (2012). Highly coordinated proteome dynamics during reprogramming of somatic cells to pluripotency. Cell Reports 2(6):1579-92

Hansson, J. and Krijgsveld, J (2013). Proteomic analysis of cell fate decision. Curr Opin Genet Dev. 23(5):540-7

Hussein SM, Puri MC, Tonge PD, Benevento M, Corso AJ, Clancy JL, Mosbergen R, Li M, Lee DS, Cloonan N, Wood DL, Munoz J, Middleton R, Korn O, Patel HR, White CA, Shin JY, Gauthier ME, Lê Cao KA, Kim JI, Mar JC, Shakiba N, Ritchie W, Rasko JE, Grimmond SM, Zandstra PW, Wells CA, Preiss T, Seo JS, Heck AJ, Rogers IM, Nagy A. (2014). Genome-wide characterization of the routes to pluripotency. Nature 516(7530):198-206

Benevento M, Tonge PD, Puri MC, Hussein SM, Cloonan N, Wood DL, Grimmond SM, Nagy A, Munoz J, Heck AJ. Proteome adaptation in cell reprogramming proceeds via distinct transcriptional networks (2014). Nat Commun. 5:5613.

Chen HH, Welling M, Bloch DB, Muñoz J, Mientjes E, Chen X, Tramp C, Wu J, Yabuuchi A, Chou YF, Buecker C, Krainer A, Willemsen R, Heck AJ, Geijsen N. DAZL limits pluripotency, differentiation, and apoptosis in developing primordial germ cells. Stem Cell Reports. 3(5):892-904.

Cabezas-Wallscheid N, Klimmeck D, Hansson J, Lipka DB, Reyes A, Wang Q, Weichenhan D, Lier A, von Paleske L, Renders S, Wünsche P, Zeisberger P, Brocks D, Gu L, Herrmann C, Haas S, Essers MA, Brors B, Eils R, Huber W, Milsom MD, Plass C, Krijgsveld J, Trumpp A. Identification of Regulatory Networks in HSCs and Their Immediate Progeny via Integrated Proteome, Transcriptome, and DNA Methylome Analysis. Cell Stem Cell (2014), 15(4):507-22

Haas S, Hansson J, Klimmeck D, Loeffler D, Velten L, Uckelmann H, Wurzer S, Prendergast AM, Schnell A, Hexel K, Santarella-Mellwig R, Blaszkiewicz S, Kuck A, Geiger H, Milsom MD, Steinmetz LM, Schroeder T, Trumpp A, Krijgsveld J, Essers MA. Inflammation-Induced Emergency Megakaryopoiesis Driven by Hematopoietic Stem Cell-like Megakaryocyte ProgenitorsCell Stem Cell. (2015), 17(4):422-34

Benevento M, Tonge PD, Puri MC, Nagy A, Heck AJ, Munoz J. Fluctuations in histone H4 isoforms during cellular reprogramming monitored by middle-down proteomics (2015). Proteomics. 15(18):3219-31.

Piazzi M, Williamson A, Lee CF, Pearson S, Lacaud G, Kouskoff V, McCubrey JA, Cocco L, Whetton AD. Quantitative phosphoproteome analysis of embryonic stem cell differentiation toward blood (2015). Oncotarget 6(13):10924-39.

Holley RJ, Tai G, Williamson AJ, Taylor S, Cain SA, Richardson SM, Merry CL, Whetton AD, Kielty CM, Canfield AE. Comparative quantification of the surfaceome of human multipotent mesenchymal progenitor cells (2015). Stem Cell Reports. 4(3):473-88.

Aspinall-O'Dea M, Pierce A, Pellicano F, Williamson AJ, Scott MT, Walker MJ, Holyoake TL, Whetton AD. Antibody-based detection of protein phosphorylation status to track the efficacy of novel therapies using nanogram protein quantities from stem cells and cell lines (2015). Nat Protoc. 10(1):149-68.

Shakiba N, White CA, Lipsitz YY, Yachie-Kinoshita A, Tonge PD, Hussein SM, Puri MC, Elbaz J, Morrissey-Scoot J, Li M, Munoz J, Benevento M, Rogers IM, Hanna JH, Heck AJ, Wollscheid B, Nagy A, Zandstra PW. CD24 tracks divergent pluripotent states in mouse and human cells (2015). Nat Commun. 6:7329.

Abraham SA, Hopcroft LE, Carrick E, Drotar ME, Dunn K, Williamson AJ, Korfi K, Baquero P, Park LE, Scott MT, Pellicano F, Pierce A, Copland M, Nourse C, Grimmond SM, Vetrie D, Whetton AD, Holyoake TL. Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells (2016). Nature 534(7607):341-6.

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Jeroen Krijgsveld, Chair

Albert Heck, Co-Chair

For more information or participation opportunities please contact office(at)hupo.org.

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