Semb Group

	Henrik Semb, Director of Stem Cell Center Professor of Functional Genetics Chief of Stem Cell and Pancreas Developmental Biology
Address:	Stem Cell and Pancreas Developmental Biology Stem cell center BMC B-10 Klinikgatan 26 221 84, Lund, Sweden Tel: 46-46-222-3159 Fax: 46-46-2223600 E-mail: Henrik.Semb@med.lu.se

Postdoctoral positions:

- Human ES cell differentiation
- Pancreas development

Main Research Topics

Our research is focused on the developmental biology of human embryonic stem cells and the pancreas. Main projects include regulation of pancreas organogenesis by mesenchymal-epithelial interactions, and differentiation of human embryonic stem cells into pancreatic insulin-producing beta cells. We believe that these studies will provide fundamental information regarding underlying causes for diabetes and development of new cell-replacement therapies of diabetes.

Regulation of pancreas development

Systematic studies of the developmental biology of the pancreas have generated important knowledge about the lineage relationship between the different pancreatic cell types and the transcriptional machinery that regulates cell fate specification. However, much remains to be learnt about the extracellular cues that specify, maintain, expand, and differentiate endocrine progenitors. Recently, we identified a novel signalling pathways involved in epithelial-mesenchymal interactions during pancreas development. Current experiments are designed to elucidate how such signaling pathways regulate tubulogenesis and differentiation/proliferation of pancreatic progenitors. Genome engineering in mice with subsequent phenotypic analysis in vivo and in vitro by explantation experiments are used.

Differentiation of human ES cells towards definitive endoderm and pancreatic cell lineages

Pancreas and islet cell transplantations provide “proof-of-concept” that cell replacement therapy is a feasible therapy in type 1 diabetes. However, cadaveric donor islets are insufficient for the present and future need in islet transplantation. The unique nature of human ES cells (hESC) to either self-renew or differentiate into most of our cell types, presumably also islet cell types, including beta-cells, suggest that these cells potentially could supply sufficient amounts of transplantable islet cells. The pancreatic islets of Langerhans originate from definitive endoderm. The path from the gastrulating embryo to the mature hormone-producing islet cell types is complex and involves sequential cell fate decisions, including formation of definitive endoderm, pancreatic endoderm, endocrine progenitors, and hormone-producing islet cell types, including beta-cells. To differentiate hESC into insulin-producing beta cells in vitro, we are recapitulating these sequential steps, with emphasis on expansion/differentiation of important beta-cell progenitors towards mature beta-cells. For this purpose, we apply current knowledge of the transcription factor network and extracellular signals that regulate these processes in vivo. To validate differentiation and to track cell lineage commitment, genome engineering is used.

Laboratory Members

Jacqueline.Ameri@med.lu.se MSc, PhD student   
Fischer, Yvonne MSc, PhD    Post Doc  

Elvira.Ganic@med.lu.se MSc, PhD student
Greiner, Thomas MSc,  PhD student
Jenny Johansson MSc, PhD student 
Kesavan, Gokul MSc, PhD student  

Hammarstedt, Maria PhD, Research Engineer

Häger, Ann-Katrin BSc, Research Engineer

Johannesson, Martina MSc, PhD student

Kobberup, Sune, PhD, Post doc

Landerman, Karolina MSc, Research Engineer 

Magnusson Marie, Animal Technician

Nilsson, Ingar, Laboratory Technician

Norrman, Karin MSc, PhD student 

Nyeng, Pia, PhD, Post doc

Wolfhagen Sand, Fredrik MSc, PhD Student 

Wu, Siqin PhD, Post doc

Selected Recent and Key Publications

1. Dahl, U., Sjödin, A., and Semb, H. Cadherins regulate aggregation of pancreatic b-cells in vivo. Development 122, 2895-2902, 1996.
2. Perl, A. -K., Wilgenbus, P., Dahl, U., Semb, H., and Christofori, G. A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature 392, 190-193, 1998.
3. Esni, F., Perl, A. -K., Täljedal, I.-B., Cremer, H., Christofori, G, and Semb, H. Neural cell adhesion molecule (N-CAM) is required for cell type segregation and normal ultrastructure in pancreatic islets. Journal of Cell Biology 144, 325-337, 1999.
4. Perl, A. -K., Dahl, U., Wilgenbus, P., Cremer, H., Semb, H., and Christofori, G. Neural cell adhesion molecule (N-CAM) modulates the metastatic dissemination of pancreatic b tumor cells. Nature of Medicine 5, 286-291, 1999.
5. Esni, F., Johansson, B. R., Radice, G. L., and Semb, H. Dorsal pancreas agenesis in N-cadherin-deficient mice. Developmental Biology 238, 202-212, 2001.
6. Heins, N., Englund, M.C.O., Sjöblom, C., Dahl, U., Tonning, A., Bergh, C., Lindahl, A., Hanson, C., and Semb, H. Derivation, characterization and differentiation of human embryonic stem cells. Stem Cells 22, 367-76, 2004.
7. Hansson, M., Tonning, A., Frandsen, U., Petri, A., Rajagopal, J., Englund, M., Heller, R.S., Håkansson, J., Fleckner, J., Nilsson Sköld, H. Melton, D., Semb, H.#, and Serup, P.# Artifactual insulin release from differentiated embryonic stem cells. Diabetes 53, 2603-9, 2004. # shared corresponding authorship.
8. Edsbagge, J., Johansson, J., Esni, F., Luo, Y., Radice, G., and Semb, H. Vascular function and sphingosine-1-phosphate regulate development of the dorsal pancreatic mesenchyme. Development, 132, 1085-1092, 2005.
9. Brolén, G.K.C., Heins, N., Edsbagge, J., and Semb, H. Signals from the embryonic mouse pancreas induce differentiation of human embryonic stem cells into cell-like insulin-producing cells. Diabetes, 54, 2867-2874, 2005.
10. X Xian, J Hakansson, A Stahlberg, P Lindblom, C Betsholtz, H Gerhardt, and H Semb (2006) Pericytes limit tumor cell metastasis. J Clin Invest 116(3):642-651.

11. International Stem Cell Initiative, Adewumi O, Aflatoonian B, Ahrlund-Richter L, Amit M, Andrews PW, Beighton G, Bello PA, Benvenisty N, Berry LS, Bevan S, Blum B, Brooking J, Chen KG, Choo AB, Churchill GA, Corbel M, Damjanov I, Draper JS, Dvorak P, Emanuelsson K, Fleck RA, Ford A, Gertow K, Gertsenstein M, Gokhale PJ, Hamilton RS, Hampl A, Healy LE, Hovatta O, Hyllner J, Imreh MP, Itskovitz-Eldor J, Jackson J, Johnson JL, Jones M, Kee K, King BL, Knowles BB, Lako M, Lebrin F, Mallon BS, Manning D, Mayshar Y, McKay RD, Michalska AE, Mikkola M, Mileikovsky M, Minger SL, Moore HD, Mummery CL, Nagy A, Nakatsuji N, O'Brien CM, Oh SK, Olsson C, Otonkoski T, Park KY, Passier R, Patel H, Patel M, Pedersen R, Pera MF, Piekarczyk MS, Pera RA, Reubinoff BE, Robins AJ, Rossant J, Rugg-Gunn P, Schulz TC, Semb H, Sherrer ES, Siemen H, Stacey GN, Stojkovic M, Suemori H, Szatkiewicz J, Turetsky T, Tuuri T, van den Brink S, Vintersten K, Vuoristo S, Ward D, Weaver TA, Young LA, Zhang W. Characterization of human embryonic stem cell lines by the International Stem Cell Initiative. Nat Biotechnol. 2007 Jul;25(7):803-16
12.Ellerström C, Strehl R, Moya K, Andersson K, Bergh C, Lundin K, Hyllner J, Semb H.
Derivation of a xeno-free human embryonic stem cell line. Stem Cells. 2006 Oct;24(10):2170-6
13. Hernebring M, Brolén G, Aguilaniu H, Semb H, Nyström T. Elimination of damaged proteins during differentiation of embryonic stem cells. Proc Natl Acad Sci U S A. 2006 May 16;103(20):7700-5