SFB 655: Cells into Tissues: Stem Cell and Progenitor Commitment and Interactions during Tissue Formation
Biology
Final Report Abstract
During its funding period (2005-2017), the SFB 655 has played a pivotal role with regard to two principal aspects – scientific advance and building a biomedical campus. As to the latter, the SFB 655 has been an essential basis for the success of the Technische Universität Dresden (TUD) in the Excellence Initiative, being a major motor in the impressive rise, over the past decade, of the Dresden biomedical research campus to international visibility. Thus, the SFB 655 laid the foundation for the DFG Research Center 111 and the Excellence Cluster Center for Regenerative Therapies Dresden in 2006 and was instrumental for the establishment of additional biomedical centers in Dresden, such as the German Center for Neuro- degenerative Diseases (DZNE), the German Center for Diabetes Research – Paul Langerhans Institute (DZD-PLID), and the German Consortium for Translational Cancer Research (DKTK). Moreover, the existence of the SFB 655 greatly promoted the Dresden International Graduate School for Biomedicine and Bioengineering (DIGS-BB), one of the largest and most prestigious PhD programs in Germany, which was awarded to the TUD in the Excellence Initiative in 2006 and renewed in 2012. As to scientific advance, the SFB 655 has pioneered the scientific vision to understand the basic biology of somatic stem and progenitor cells in the context of tissue formation and, eventually, clinical application. Here, the SFB 655 has been focusing on two paradigmatic somatic stem cell systems – the nervous system and the hematopoietic system – and has brought together the traditionally separate disciplines of cell biology, developmental and evolutionary biology, molecular bioengineering and medicine, establishing the first institutional forum in Germany with this concept. For the nervous system, major themes included the dissection of neural stem and progenitor cell subtypes in various systems and the analysis, at the molecular level, of signaling pathways that govern neu- ral stem and progenitor cell proliferation versus differentiation, and of their impact on neurogenesis. For the hematopoietic system, a major theme was the dissection of the hematopoietic niche at the molecular, cell biological and bioengineering level. The concept of integrating research on human cells and tissues with that on various vertebrate model organisms (zebrafish, axolotl, and mouse) has been instrumental for uncovering common principles of tissue formation during development and adulthood, in disease, and in the context of evolution. Thanks to this integration, the discoveries made in the SFB 655 range from the functional analysis of key molecular players to the study of the complex behavior of stem and progenitor cells in tissues. A tremendous advance has been the implementation of the "Genome Center" as an SFB 655 Z-project, which has been critically important not only for SFB 655 members, but also for the whole Dresden biomedical campus. The SFB 655 matured further as a platform supporting the career of young scientists. Thus, the SFB 655 has confirmed its track record with regard to promoting advanced career stages, with six project leaders receiving offers for professorship positions. In summary, the SFB 655 had delivered in producing excellent research results, stabilizing the core of a growing campus engaged in one of the most promising areas of biomedicine, and training and in promoting researchers of the future.
Publications
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Pearce G, Audzevich T, Jessberger R
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Audzevich T, Jessberger R
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Kyritsis N, Kizil C, Zocher S, Kroehne V, Kaslin J, Freudenreich D, Iltzsche A, Brand M
(See online at https://doi.org/10.1126/science.1228773) - (2012). Polycomb group ring finger 1 cooperates with Runx1 in regulating differentiation and self renewal of hematopoietic cells. Blood 119, 4152-61
Ross K, Sedello AK, Putz G, Paszkowski-Rogacz M, Bird AW, Hubner N, Mann M, Waskow C, Stocking C, and Buchholz F
(See online at https://doi.org/10.1182/blood-2011-09-382390) - (2012). Polymorphism rs11085226 in the gene encoding polypyrimidine-tract binding protein 1 negatively affects glucose-stimulated insulin secretion. PLoS One 7, e46154
Heni M, Ketterer C, Wagner R, Linder K, Böhm A, Herzberg-Schäfer SA, Machicao F, Knoch KP, Fritsche A, Staiger H, Häring HU, Solimena M
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Mchedlishvili L, Mazurov V, Grassme KS, Goehler K, Robl B, Tazaki A, Roensch K, Duemmler A, Tanaka EM
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Eskan MA, Jotwani R, Abe T, Chmelar J, Lim JH, Liang S, Ciero P, Krauss J, Li F, Rauner M, Hofbauer LC, Choi EY, Chung KJ, Hashim A, Curtis M, Chavakis T, Hajishengallis G
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Walker TL, Wierick A, Sykes AM, Waldau B, Corbeil D, Carmeliet P, Kempermann G
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Paridaen JTML, Wilsch-Bräuninger M, Huttner WB
(See online at https://doi.org/10.1016/j.cell.2013.08.060) - (2013). Progressive Specification Rather than Intercalation of Segments During Limb Regeneration. Science 342: 1375-1379
Roensch K, Tazaki A, Chara O, Tanaka EM
(See online at https://doi.org/10.1126/science.1241796) - (2013). Regulation of cerebral cortex size and folding by expansion of basal progenitors. EMBO J, 32:1817-28
Nonaka-Kinoshita M, Reillo I, Artegiani B, Martinez M, Nelson M, Borrell V, Calegari F
(See online at https://doi.org/10.1038/emboj.2013.96) - (2013). The histone demethylase UTX regulates stem cell migration and hematopoiesis. Blood 121, 2462-73
Thieme S, Gyárfás T, Richter C, Ozhan G, Fu J, Alexopulou D, Muders MH, Michalk I, Jakob C, Dahl A, Klink B, Bandola J, Bachmann M, Schröck E, Buchholz F, Stewart AF, Weidinger G, Anastassiadis K, Brenner S
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(See online at https://doi.org/10.1038/nmeth.2523) - (2014). Hes3 is expressed in the adult pancreatic islet and regulates gene expression, cell growth, and insulin release. J Biol Chem, 289, 35503-16
Masjkur J, Arps-Forker C, Poser SW, Nikolakopoulou P, Toutouna L, Chenna R, Chavakis T, Chatzigeogiou A, Chen LS, Dubrovska A, Choudhary P, Uphues I, Mark M, Bornstein SR, Androutsellis- Theotokis A
(See online at https://doi.org/10.1074/jbc.m114.590687) - (2014). Kit Regulates HSC Engraftment across the Human-Mouse Species Barrier. Cell Stem Cell 15, 227-38
Cosgun KN, Rahmig S, Mende N, Reinke S, Hauber I, Schäfer C, Petzold A, Weisbach H, Heidkamp G, Purbojo A, Cesnjevar R, Platz A, Bornhäuser M, Schmitz M, Dudziak D, Hauber J, Kirberg J, Waskow C
(See online at https://doi.org/10.1016/j.stem.2014.06.001) - (2014). The age and genomic integrity of neurons after cortical stroke in humans. Nat Neurosci 17:801-3
Huttner WB, Bergmann O, Salehpour M, Rácz A, Tatarishvili J, Dahl A, et al.
(See online at https://doi.org/10.1038/nn.3706) - (2015). Brain oxygen tension controls the expansion of outer subventricular zone-like basal progenitors in the developing mouse brain. Development 142, 2904-15
Wagenführ L, Meyer AK, Braunschweig L, Marrone L, Storch A
(See online at https://doi.org/10.1242/dev.121939) - (2015). Ccnd1/Cdk4-mediated cell cycle progression provides a competitive advantage for human hemantopoietic stem cells in vivo. J Exp Med 212, 1171-1183
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(See online at https://doi.org/10.1084/jem.20150308) - (2015). Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion. Science 347:1465-70
Florio M, Albert M, Taverna E, Namba T, Brandl H, Lewitus E, Haffner C, Sykes A, Wong FK, Peters J, Guhr E, Klemroth S, Prüfer K, Kelso J, Naumann R, Nüsslein I, Dahl A, Lachmann R, Pääbo S, Huttner WB
(See online at https://doi.org/10.1126/science.aaa1975) - (2015). RNAi profiling of primary human AML cells identifies ROCK1 as a therapeutic target and nominates fasudil as an antileukemic drug. Blood 125, 3760-8
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(See online at https://doi.org/10.1182/blood-2014-07-590646) - (2015). Tox: a multifunctional transcription factor and novel regulator of mammalian corticogenesis. EMBO J 34, 896-910
Artegiani B, de Jesus Domingues AM, Bragado Alonso A, Brandl E, Massalini S, Dahl A, Calegari F
(See online at https://doi.org/10.15252/embj.201490061) - (2015). Valproic acid enhances neuronal differentiation of sympathoadrenal progenitor cells. Mol Psychiatry 20, 941-50
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(See online at https://doi.org/10.1038/mp.2015.3) - (2016). Independent modes of ganglion cell translocation guide correct lamination in the zebrafish retina. J Cell Biol 215, 259-75
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(See online at https://doi.org/10.1083/jcb.201604095) - (2016). The bulk of the hematopoietic stem cell population is dispensable for murine steady-state and stress hematopoiesis. Blood 128, 2285-96
Schoedel KB, Morcos MN, Zerjatke T, Roeder I, Grinenko T, Voehringer D, Gothert JR, Waskow C, Roers A, Gerbaulet A
(See online at https://doi.org/10.1182/blood-2016-03-706010) - (2016). The effects of stress on brain and adrenal stem cells. Mol Psychiatry 21, 590-3
Rubin de Celis MF, Bornstein SR, Androutsellis-Theotokis A, Andoniadou CL, Licinio J, Wong ML, Ehrhart-Bornstein M
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Chung KJ, Chatzigeorgiou A, Economopoulou M, Garcia-Martin R, Alexaki VI, Mitroulis I, Nati M, Gebler J, Ziemssen T, Goelz SE, Phieler J, Lim JH, Karalis KP, Papayannopoulou T, Blüher M, Hajishengallis G, Chavakis T
(See online at https://doi.org/10.1038/ni.3728) - (2017). Clonal fate-mapping quantifies the number of haematopoietic stem cells that arise during development. Nature Cell Biol 19,17-27
Henninger J, Santoso B, Hans S, Durand E, Moore J, Mosiman C, Brand M, Traver D, Zon L
(See online at https://doi.org/10.1038/ncb3444) - (2017). Donor cell leukemia: evidence for multiple preleukemic clones and parallel long term clonal evolution in donor and recipient. Leukemia 31, 1637- 40
Herold S, Kuhn M, Bonin MV, Stange T, Platzbecker U, Radke J, Lange T, Sockel K, Gutsche K, Schetelig J, Röllig C, Schuster C, Roeder I, Dahl A, Mohr B, Serve H, Brandts C, Ehninger G, Bornhäuser M, Thiede C
(See online at https://doi.org/10.1038/leu.2017.104) - (2017). Myelodysplastic syndromes and bone loss in mice and men. Leukemia 31,1003-7
Weidner H, Rauner M, Trautmann F, Schmitt J, Balaian E, Mies A, Helas S, Baschant U, Khandanpour C, Bornhäuser M, Hofbauer LC, Platzbecker U
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Alissafi T, Banos A, Boon L, Sparwasser T, Ghigo A, Wing K, Vassilopoulos D, Boumpas D, Chavakis T, Cadwell K, Verginis P
(See online at https://doi.org/10.1172/jci92079)
