Project Details
SFB 873: Maintenance and Differentiation of Stem Cells in Development und Disease
Subject Area
Medicine
Biology
Biology
Term
from 2010 to 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 122491522
The long-term goal of this Collaborative Research Centre is to define the regulatory principles underlying the balance between stem cell maintenance and differentiation in diverse organisms on a mechanistic level. This objective will be accomplished by studying the intrinsically and extrinsically controlled self-renewal process in various model systems including Arabidopsis, Hydra, Drosophila, Medaka, Xenopus, as well as mouse and human. The basic principles controlling stem cell self-renewal and differentiation are strikingly conserved during evolution, despite the fact that individual pathways can differ between various stem cell systems of the same organism as well as between homologous stem cell niches in different organisms. Since the regulatory pathways that control stem cell function in highly complex mammalian systems are often difficult to study and frequently show significant molecular redundancy, our consortium will also take advantage of simpler model systems to illuminate the cellular and molecular mechanisms governing stem cell function. Thus the overall objective of this Consortium is to bridge the gap between experimentally amenable model systems and highly complex mammalian systems. By comparing divergent and conserved modules of stem cell control across the kingdoms of life, this Collaborative Research Centre will fundamentally advance our understanding of the principles and molecular mechanisms that control stem cell function during development, homeostasis, injury repair and disease. The Collaborative Research Centre will, therefore, focus on two major areas: (1) Mechanisms of stem cell self-renewal: using suitable model systems of lower complexity we will elucidate essential molecular mechanisms of stem cell control and identify conserved and divergent regulatory modules governing the fundamental decision process of self-renewal and differentiation. These results will serve as a resource for comparative studies in more complex systems including mouse and human to define the pathways regulating stem cell fate during development and disease. (2) Cell-cell interactions in the stem cell niche: in addition to intrinsic mechanisms, extrinsic cues mediated by the microenvironment, commonly referred to as the stem cell niche do not only maintain stem cell fate but also control the balance between stem cell self-renewal and differentiation. This group of subprojects will focus on the nature and function of the cell types comprising the niche and on the molecules involved in the bi-directional interactions between the niche and the corresponding stem cells in normal and diseased states. Cross species and cross kingdom comparisons will be used to identify the most relevant components that generate the functional stem cell-niche units.
DFG Programme
Collaborative Research Centres
Completed projects
- A01 - Stem cell plasticity in Hydra (Project Head Holstein, Thomas W. )
- A02 - Understanding Drosophila intestinal stem cell-derived tumors (Project Head Edgar, Bruce A. )
- A03 - Control of stem cell identity and homeostasis in the ciliary marginal zone of the vertebrate retina (Project Head Wittbrodt, Joachim )
- A06 - Interactions of signaling pathways during intestinal stem cell self-renewal and differentiation (Project Head Boutros, Michael )
- A07 - Control of stem cell fate by key regulators of post-embryonic hematopoiesis (Project Heads Glimm, Hanno ; von Kalle, Christof )
- A08 - Generation of human induced pluripotent stem cells (iPSCs) and their use for the generation of a skin equivalent (Project Head Utikal, Jochen )
- A09 - The role of IGFBPs/IGFBPrPs in the differentiation of extra-embryonic tissue (Project Head Steinbeisser, Herbert )
- A11 - Mechanisms of niche – stem cell unit origin and maintenance (Project Head Centanin, Ph.D., Lazaro )
- A12 - Studying lung stem cells in tissue maintenance, repair, and cancer (Project Heads Glimm, Hanno ; Scholl, Claudia )
- A13 - Clonal heterogeneity in leukemic and 'pre-leukemic' stem cells from patients with AML (Project Head Lutz, Christoph )
- A14 - Functional role of centrosomes and cilia in stem cells (Project Head Pereira, Gislene )
- A16 - Transcriptional complexes and chromatin reorganization in lineage choices and differentiation of embryonic stem cells (Project Head Dobreva, Gergana )
- A17 - Regulatory and phenotypic evolution of the male mammalian germline and underlying stem cells (Project Head Kaessmann, Ph.D., Henrik )
- B01 - Towards a mechanistic framework of plant stem cell control (Project Head Lohmann, Jan )
- B02 - Molecular and cellular control of the Drosophila male stem cell niche (Project Head Lohmann, Ingrid )
- B03 - Role of Wnt signaling in embryonic neural stem cells (Project Head Niehrs, Ph.D., Christof )
- B04 - A novel level of regulation of normal and leukemic stem cell hierarchies by differential polyad-enylation of key transcripts (Project Head Trumpp, Ph.D., Andreas )
- B05 - The effect of IFNa signaling on hematopoietic stem cells (Project Head Essers, Marieke )
- B06 - Endothelial cell fate and angiocrine control of stem cell function (Project Head Augustin, Hellmut G. )
- B07 - Mechanism of dynamic homing and migration of human hematopoietic stem cells in the bone marrow niche using quantitative tools (Project Heads Dietrich, Sascha ; Tanaka, Motomu )
- B08 - Mathematical modeling of stem cell renewal and differentiation (Project Head Marciniak-Czochra, Anna )
- B09 - Mechanisms of regulation of stem cells in the adult brain (Project Head Martin-Villalba, Ana )
- B10 - Intrinsic and microenvironment factors regulating the stem cell maintenance and the niche in normal and neoplastic epidermal cells (Project Head Boukamp, Petra )
- B11 - Fate mapping of hematopoietic stem cell activity under steady state and challenges (Project Heads Höfer, Thomas ; Rodewald, Hans-Reimer )
- B12 - Spatio-temporal specificity of cambium stem cell signaling (Project Head Greb, Thomas )
- B13 - HSCs under acute and chronic inflammatory stress (Project Heads Essers, Marieke ; Milsom, Michael )
- B14 - Unraveling the mechanisms that regulate vascular properties in neurogenic niches: role of neural stem cells (Project Head Ruiz de Almodovar Egea, Ph.D., Carmen )
- Z01 - Administration and coordination (Project Head Lohmann, Jan )
- Z02 - Flow cytometry core unit (Project Heads Eckstein, Volker ; Müller-Tidow, Carsten )
- Z03 - Advanced Light Microscopy (Project Head Engel, Ulrike )
- Z04 - Bioinformatic analysis and comparative data mining (Project Heads Kaessmann, Ph.D., Henrik ; Lohmann, Jan )
Applicant Institution
Ruprecht-Karls-Universität Heidelberg
Participating Institution
Deutsches Krebsforschungszentrum (DKFZ)
Spokespersons
Professor Dr. Anthony D. Ho, until 6/2014; Professor Dr. Jan Lohmann, since 7/2014