@article{RosalesAlvarezRettkowskiHermanetal.2023,
  author    = {Rosales-Alvarez, Reyna Edith and Rettkowski, Jasmin and Herman, Josip Stefan and Dumbović, Gabrijela and Cabezas-Wallscheid, Nina and Gr{\"u}n, Dominic},
  title     = {VarID2 quantifies gene expression noise dynamics and unveils functional heterogeneity of ageing hematopoietic stem cells},
  series = {Genome Biology},
  volume    = {24},
  journal   = {Genome Biology},
  doi       = {10.1186/s13059-023-02974-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358042},
  year      = {2023},
  abstract  = {Variability of gene expression due to stochasticity of transcription or variation of extrinsic signals, termed biological noise, is a potential driving force of cellular differentiation. Utilizing single-cell RNA-sequencing, we develop VarID2 for the quantification of biological noise at single-cell resolution. VarID2 reveals enhanced nuclear versus cytoplasmic noise, and distinct regulatory modes stratified by correlation between noise, expression, and chromatin accessibility. Noise levels are minimal in murine hematopoietic stem cells (HSCs) and increase during differentiation and ageing. Differential noise identifies myeloid-biased Dlk1+ long-term HSCs in aged mice with enhanced quiescence and self-renewal capacity. VarID2 reveals noise dynamics invisible to conventional single-cell transcriptome analysis.},
  language  = {en}
}
@article{SolimandoPalumboPragnelletal.2022,
  author    = {Solimando, Antonio G. and Palumbo, Carmen and Pragnell, Mary Victoria and Bittrich, Max and Argentiero, Antonella and Krebs, Markus},
  title     = {Aplastic anemia as a roadmap for bone marrow failure: an overview and a clinical workflow},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {19},
  issn      = {1422-0067},
  doi       = {10.3390/ijms231911765},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290440},
  year      = {2022},
  abstract  = {In recent years, it has become increasingly apparent that bone marrow (BM) failures and myeloid malignancy predisposition syndromes are characterized by a wide phenotypic spectrum and that these diseases must be considered in the differential diagnosis of children and adults with unexplained hematopoiesis defects. Clinically, hypocellular BM failure still represents a challenge in pathobiology-guided treatment. There are three fundamental topics that emerged from our review of the existing data. An exogenous stressor, an immune defect, and a constitutional genetic defect fuel a vicious cycle of hematopoietic stem cells, immune niches, and stroma compartments. A wide phenotypic spectrum exists for inherited and acquired BM failures and predispositions to myeloid malignancies. In order to effectively manage patients, it is crucial to establish the right diagnosis. New theragnostic windows can be revealed by exploring BM failure pathomechanisms.},
  language  = {en}
}
@article{ScognamiglioCabezasWallscheidThieretal.2016,
  author    = {Scognamiglio, Roberta and Cabezas-Wallscheid, Nina and Thier, Marc Christian and Altamura, Sandro and Reyes, Alejandro and Prendergast, {\´A}ine M. and Baumg{\"a}rtner, Daniel and Carnevalli, Larissa S. and Atzberger, Ann and Haas, Simon and von Paleske, Lisa and Boroviak, Thorsten and W{\"o}rsd{\"o}rfer, Philipp and Essers, Marieke A. G. and Kloz, Ulrich and Eisenman, Robert N. and Edenhofer, Frank and Bertone, Paul and Huber, Wolfgang and van der Hoeven, Franciscus and Smith, Austin and Trumpp, Andreas},
  title     = {Myc depletion induces a pluripotent dormant state mimicking diapause},
  series = {Cell},
  volume    = {164},
  journal   = {Cell},
  number    = {4},
  doi       = {10.1016/j.cell.2015.12.033},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-190868},
  pages     = {668-680},
  year      = {2016},
  abstract  = {Mouse embryonic stem cells (ESCs) are maintained in a naive ground state of pluripotency in the presence of MEK and GSK3 inhibitors. Here, we show that ground-state ESCs express low Myc levels. Deletion of both c-myc and N-myc (dKO) or pharmacological inhibition of Myc activity strongly decreases transcription, splicing, and protein synthesis, leading to proliferation arrest. This process is reversible and occurs without affecting pluripotency, suggesting that Myc-depleted stem cells enter a state of dormancy similar to embryonic diapause. Indeed, c-Myc is depleted in diapaused blastocysts, and the differential expression signatures of dKO ESCs and diapaused epiblasts are remarkably similar. Following Myc inhibition, pre-implantation blastocysts enter biosynthetic dormancy but can progress through their normal developmental program after transfer into pseudo-pregnant recipients. Our study shows that Myc controls the biosynthetic machinery of stem cells without affecting their potency, thus regulating their entry and exit from the dormant state.},
  language  = {en}
}
@article{GiampaoloWojcikSerflingetal.2017,
  author    = {Giampaolo, Sabrina and W{\´o}jcik, Gabriela and Serfling, Edgar and Patra, Amiya K.},
  title     = {Interleukin-2-regulatory T cell axis critically regulates maintenance of hematopoietic stem cells},
  series = {Oncotarget},
  volume    = {8},
  journal   = {Oncotarget},
  number    = {18},
  doi       = {10.18632/oncotarget.16377},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170947},
  pages     = {29625-29642},
  year      = {2017},
  abstract  = {The role of IL-2 in HSC maintenance is unknown. Here we show that Il2\(^{-/-}\) mice develop severe anomalies in HSC maintenance leading to defective hematopoiesis. Whereas, lack of IL-2 signaling was detrimental for lympho- and erythropoiesis, myelopoiesis was enhanced in Il2\(^{-/-}\) mice. Investigation of the underlying mechanisms of dysregulated hematopoiesis in Il2\(^{-/-}\) mice shows that the IL-2-T\(_{reg}\) cell axis is indispensable for HSC maintenance and normal hematopoiesis. Lack of T\(_{reg}\) activity resulted in increased IFN-γ production by activated T cells and an expansion of the HSCs in the bone marrow (BM). Though, restoring T\(_{reg}\) population successfully rescued HSC maintenance in Il2\(^{-/-}\) mice, preventing IFN-γ activity could do the same even in the absence of T\(_{reg}\) cells. Our study suggests that equilibrium in IL-2 and IFN-γ activity is critical for steady state hematopoiesis, and in clinical conditions of BM failure, IL-2 or anti-IFN-γ treatment might help to restore hematopoiesis.},
  language  = {en}
}
@phdthesis{Krohne2005,
  author    = {Krohne, Katharina},
  title     = {Die Rolle des Proteins VASP f{\"u}r die Proliferation und Differenzierung h{\"a}matopoetischer Stammzellen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-15639},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2005},
  abstract  = {Im Rahmen der Arbeit wurden in mehreren Teilprojekten die Eigenschaften und Funktionen des Vasodilatator stimulierenden Phosphoproteins (VASP) untersucht. Es wurde ein neuer Antik{\"o}rper (5C6) charakterisiert, der f{\"u}r an Serin157 phosphoryliertes VASP spezifisch sein sollte. Es konnte gezeigt werden, dass der 5C6 Antik{\"o}rper spezifisch VASP erkennt, welches an der Stelle Serin157 phosphoryliert ist. Auch konnten mit dem neuen Antik{\"o}rper Ergebnisse best{\"a}tigt werden, die vorher mit anderen Methoden erhoben wurden, n{\"a}mlich, dass Serin157 sowohl cAMP- als auch cGMP-vermittelt phosphoryliert wird. Der Antik{\"o}rper 5C6 stellte sich als ein guter Marker f{\"u}r die Phosphorylierung von VASP an Serin157 durch die PKA dar und erm{\"o}glichte, die Zeitkinetik der VASP-Phosphorylierung zu beschreiben. In einem weiteren Projekt wurde die Rolle des Proteins VASP bei der Proliferation und Differenzierung von Knochenmark-Stammzellen zu Megakaryozyten und Thrombozyten untersucht. Die Stammzellen wurden zus{\"a}tzlich zu Wachstumsfaktoren mit unterschiedlichen Dosen eines cGMP-Analogons stimuliert. Es zeigte sich hierbei, dass 8-pCPT-cGMP einen dualen, konzentrationsabh{\"a}ngigen Effekt auf die Proliferation und die Differenzierung h{\"a}matopoetischer Stammzellen von Wildtypm{\"a}usen hat. Niedrige Dosen hemmten die Proliferation und f{\"o}rderten die Differenzierung, dagegen hatten h{\"o}here Konzentrationen einen proliferationsf{\"o}rdernden und differenzierungshemmenden Effekt auf die Stammzellen. Im Vergleich hierzu ergab eine Stimulation mit 8-pCPT-cGMP bei VASP knock out M{\"a}usen immer einen proliferationsf{\"o}rdernden Effekt, hingegen einen hemmenden Effekt auf die Differenzierung der h{\"a}matopoetischen Stammzellen. Bei den knock out Zellen f{\"u}hrten h{\"o}here Konzentrationen lediglich zu einer st{\"a}rkeren Reaktion als niedrige.},
  language  = {de}
}