SFB 655:  Cells into Tissues: Stem Cell and Progenitor Commitment and Interactions during Tissue Formation

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

• (2006). cAMP-dependent phosphorylation of PTB1 promotes the expression of insulin secretory granule proteins in beta cells. Cell Metabolism 3, 123-134
  Knoch KP, Meisterfeld R, Kersting S, Bergert H, Altkrüger A, Wegbrod C, Jäger M, Saeger HD, and Solimena M
  
• (2006). Signaling protein SWAP-70 is required for efficient B cell homing to lymphoid organs. Nature Immunol 7, 827-34
  Pearce G, Angeli V, Randolph GJ, Junt T, von Adrian U, Schnittler HJ, Jessberger R
  
• (2007). A clonal analysis of neural progenitors during axolotl spinal cord regeneration reveals evidence for both spatially restricted and multipotent progenitors. Development 134, 2083-93
  McHedlishvili L, Epperlein HH, Telzerow A, Tanaka EM
  
• (2007). Midbody and primary cilium of neural progenitors release extracellular membrane particles enriched in the stem cell marker prominin-1. J Cell Biol 176, 483-95
  Dubreuil V, Marzesco AM, Corbeil D, Huttner W, Wilsch-Bräuninger M
  
• (2008). Del-1 is an endogenous inhibitor of leukocyte-endothelial adhesion limiting inflammatory cell recruitment. Science 322,1101-4
  Choi EY, Chavakis E, Czabanka MA, Langer HF, Fraemohs L, Economopoulou M, Orlandi A, Kundu RK, Zheng YY, Prieto DR, Ballantyne CM, Constant SL, Aird W, Papayannopoulou T, Gahmberg CG, Udey MC, Vajkoczy P, Quertermous T, Dimmeler S, Weber C, Chavakis T
  
• (2008). Functional immobilization of signaling proteins enables control of stem cell fate. Nat Methods 5, 645-50
  Alberti K, Davey RE, Onishi K, George S, Salchert K, Seib FP, Bornhäuser M, Pompe T, Nagy A, Werner C, Zandstra PW
  
• (2008). SWAP-70 deficiency causes highaffinity plasma cell generation despite impaired germinal center formation. Blood 111, 2714-2724
  Quemeneur L, Angeli V, Chopin M, and Jessberger R
  
• (2009). Combining SDF-1/CXCR4 antagonism and chemotherapy in relapsed acute myeloid leukemia. Leukemia 23, 393-96
  Fierro FA, Brenner S, Oelschlaegel U, Jacobi A, Knoth H, Ehninger G, Illmer T, Bornhäuser M
  
• (2009). Stem Cells in the Adult Zebrafish Cerebellum: Initiation and Maintenance of a Novel Stem Cell Niche. J Neuroscience 29, 6142-6153
  Kaslin J, Ganz J, Geffarth M, Grandel H, Hans S, Brand M
  
• (2010). Polarization and migration of hematopoietic stem and progenitor cells rely on RhoA/ROCK I pathway and an active reorganization of the microtubule network. J Biol Chem. 285: 31661-31671
  Fonseca AV, Freund D, Bornhäuser M, Corbeil D
  
• (2010). SYK regulates B cell migration by phosphorylation of the F-actin interacting protein SWAP-70. Blood 117, 1574-1584
  Pearce G, Audzevich T, Jessberger R
  
• (2011). Proliferating versus differentiating stem and cancer cells exhibit distinct midbody-release behaviour. Nat Commun 2, 503
  Ettinger AW, Wilsch-Bräuninger M, Marzesco AM, Bickle M, Lohmann A, Maliga Z, Karbanová J, Corbeil D, Hyman AA, Huttner WB
  
• Verfahren und Mittel zur Identifizierung von Substanzen, welche die IgE- Produktion hemmen. German patent, DE 10 2010 027 827 B3, granted 16.06.2011
  Audzevich T, Jessberger R
  
• (2012). Acute inflammation initiates the regenerative response in the adult zebrafish brain. Science 338:1353-6
  Kyritsis N, Kizil C, Zocher S, Kroehne V, Kaslin J, Freudenreich D, Iltzsche A, Brand M
  
• (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
  
• (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
  
• (2012). Reconstitution of the central and peripheral nervous system during salamander tail regeneration. PNAS 109: E2258-66
  Mchedlishvili L, Mazurov V, Grassme KS, Goehler K, Robl B, Tazaki A, Roensch K, Duemmler A, Tanaka EM
  
• (2012): The leukocyte integrin antagonist Del-1 inhibits IL-17-mediated inflammatory bone loss. Nature Immunol 13, 465-73
  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
  
• (2013) Prominin-1 allows prospective isolation of neural stem cells from the adult murine hippocampus. J Neurosci 33:3010-3024
  Walker TL, Wierick A, Sykes AM, Waldau B, Corbeil D, Carmeliet P, Kempermann G
  
• (2013). Asymmetric inheritance of centrosomeassociated primary cilium membrane directs ciliogenesis after cell division. Cell 155, 333-344
  Paridaen JTML, Wilsch-Bräuninger M, Huttner WB
  
• (2013). Progressive Specification Rather than Intercalation of Segments During Limb Regeneration. Science 342: 1375-1379
  Roensch K, Tazaki A, Chara O, Tanaka EM
  
• (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
  
• (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
  
• (2013). Tightly anchored tissue-mimetic matrices as instructive stem cell microenvironments. Nature Methods 10, 788-94
  Prewitz M, Seib PF, von Bonin M, Niehae C, Friedrichs J, Stißel A, Müller K, Anastassiadis K, Waskow C, Hoflack B, Bornhäuser M, Werner C
  
• (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
  
• (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
  
• (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.
  
• (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
  
• (2015). Ccnd1/Cdk4-mediated cell cycle progression provides a competitive advantage for human hemantopoietic stem cells in vivo. J Exp Med 212, 1171-1183
  Mende N, Kuchen E, Lesche M, Grinenko T, Kokkaliaris Kd, Hanenberg H, Lindemann D, Dahl A, Platz A, Hoefer T, Calegari F, Waskow C
  
• (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
  
• (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
  Wermke M, Camgoz A, Paszkowski-Rogacz M, Thieme S, von Bonin M, Dahl A, Platzbecker U, Theis M, Ehninger G, Brenner S, Bornhäuser M, Buchholz F
  
• (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
  
• (2015). Valproic acid enhances neuronal differentiation of sympathoadrenal progenitor cells. Mol Psychiatry 20, 941-50
  Vukićević V, Qin N, Balyura M, Eisenhofer G, Wong ML, Licinio J, Bornstein SR, Ehrhart-Bornstein M
  
• (2016). Independent modes of ganglion cell translocation guide correct lamination in the zebrafish retina. J Cell Biol 215, 259-75
  Icha J, Kunath C, Rocha-Martins M, Norden C
  
• (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
  
• (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
  
• (2017). A self-sustained loop of inflammation-driven inhibition of beige adipogenesis in obesity. Nature Immunol 18, 654-64
  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
  
• (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
  
• (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
  
• (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
  
• (2017). Tregs restrain dendritic cell autophagy to ameliorate autoimmunity. J Clin Invest 127: 2789-2804
  Alissafi T, Banos A, Boon L, Sparwasser T, Ghigo A, Wing K, Vassilopoulos D, Boumpas D, Chavakis T, Cadwell K, Verginis P
  

Completed projects