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Hematopoietic stem cells (HSCs) are at the foundation of the hematopoietic system. Endowed with multi-lineage differentiation and long-term self-renewal properties, HSCs have the capacity to replenish the entire blood system, thereby meeting the constant need for short-lived blood cell types throughout life. In all vertebrates, the first HSCs originate during embryonic life. Specialized hemogenic endothelial cells bud from the endothelial lining of the main arteries, such as the aorta, to undergo an endothelial-to-hematopoietic transition (EHT). EHT leads to the formation of hematopoietic cells that organize in clusters (intra-aortic hematopoietic clusters; IAHCs) that remain transiently attached to the endothelium. The number of IAHC cells peaks at E10.5, when the first HSCs start to be detected in the aorta. IAHCs contain very few HSCs and committed erythroid-myeloid progenitors, and are mainly composed of HSC precursors (pre-HSCs) that progressively mature towards HSCs. The decrease of IAHC cell number in the aorta coincides with the appearance of HSCs in the fetal liver (FL). Given the similar number of aortic pre-HSCs and HSCs in FL, pre-HSCs most likely migrate from the aorta to the FL to complete their maturation process there. This maturation, followed by expansion of the HSCs, leads to the formation of the adult HSC pool that colonizes the bone marrow (BM), the main site of hematopoiesis in adulthood. The restricted spatial and temporal production of HSCs during embryonic development is regulated by a complex network of cell-intrinsic and -extrinsic factors. Obtaining a better understanding of HSC regulation is the main focus of this thesis. The present work, begins to elucidate the complex regulatory network that controls HSC generation and pre-HSC maturation at different levels. We show that cell-intrinsic factors, such as molecular changes in the transcription factor network, allow for the transition from an endothelial to a hematopoietic program in the aorta. At the cellular level, complex rearrangements of cytoskeletal elements are needed for the successful emergence from the endothelium. The maintenance of the initiated stem cell program is critically dependent on the interaction of the cell with the surrounding microenvironment and its ability to respond to gradients of soluble factors. Impaired intra-cellular trafficking of receptors such as c-Kit, which mediates the cross-talk between HSCs and the niche factors, results in the loss of stem cell properties. Our results suggest that the appropriate timing and number of receptors on the cellular surface—partly controlled by vesicular trafficking through the Golgi and degradation through the endo/lysosomal pathway—is pivotal. Cell-extrinsic signals, such as secreted ligands from the immediate microenvironment, are another critical part of the regulatory landscape of HSC generation. Our work indicates that the availability of those ligands to bind to their cognate receptors at the cell surface is further modulated by the extracellular matrix and its complexity. Understanding the regulatory network that allows for de novo generation of HSCs during embryonic development is crucial to improve our current efforts to produce these precious cells in vitro, with wider significance for stem cell therapies and regenerative medicine.

Diese Arbeit beschäftigt sich mit der literarischen Darstellung der Shoah am Beispiel der Werke „Eine Seele aus Holz. Erzählungen“, „Selbstporträt“ und „Landschaft in Beton“ Jakov Linds. Als Jude war der Autor unmittelbar von der nationalsozialistischen Verfolgungs- und Tötungsmaschinerie betroffen, und verarbeitete diese Erlebnisse auch auf unterschiedlichste Weise in seinen Schriften. Die Forschungsfrage konzentriert sich auf die Art und Weise wie die Shoah dargestellt und erzählt wird. Es geht um die Analyse stilistischer Besonderheiten und keinesfalls um die Überprüfung der Texte auf biografische oder historische Authentizität. Konkret soll also herausgefunden werden, welcher literarischer Mittel sich Lind bedient, um die Shoah darzustellen. Um die Texte in einen Kontext zu betten, widmet sich die vorliegende Arbeit auch ausführlich den Debatten über die Frage nach der generellen Erzählbarkeit der Shoah und diesbezüglich gängiger und anerkannter Darstellungsweisen. Das Interessante an den ausgewählten Texten ist, dass sie als Antwort auf den in Österreich lange vorherrschenden Verdrängungsdiskurs hinsichtlich der Ereignisse der Shoah gelesen werden können. Linds Darstellungsrepertoire reicht von brutaler, ungeschminkter Realität, die von keinerlei Pathos gekennzeichnet ist, bis hin zu Groteske, Ironie und Komik. In seiner Art die Shoah zu erzählen, sprengt er somit sämtliche Darstellungstabus und lässt den Leser durch die Kombination der verschiedenen literarischen Techniken oft sehr verstört zurück. Nicht zuletzt durch die postmoderne Darstellung wird dem Leser ein neuer und anderer Blick auf die Shoah ermöglicht. Anstatt die Perspektive eines Chronisten oder leidenden Opfers einzunehmen, bedient sich Lind verschiedenster Darstellungsweisen und Erzählhaltungen wie der Kinder- oder Schelmenperspektive. Der Autor zeigt außerdem, dass nach den schrecklichen Ereignissen nichts mehr so ist wie zuvor. Als grotesk empfundene Werte und Handlungen sind plötzlich der Regelfall und gelten als Normal in einer nunmehr verkehrten Welt., This diploma thesis seeks to explore the literary representation of the Shoah in the works “Soul of Wood”, “Counting My Steps” and “Landscape in Concrete” by Jakov Lind. Being Jewish himself, he was immediately affected by the National Socialist machinery of persecution and homicide, and consequently came to terms with these experiences through various approaches in his works. The research question hereby lies on how the Shoah is depicted and narrated, leaving aside questions relating to biographical and historical authenticity, instead rather focusing on an analysis of stylistic features. What is interesting about the texts chosen is that they can be read in a way, giving answers to the repressed discourse on the events circling around the Shoah that prevailed in Austria for a long time. Lind’s repertoire of representation ranges from mirroring a brutal, unflattering reality, devoid of any pathos, to grotesque, irony and humor. Through this strategy of combining multitudinous literary devices, he bursts all taboos relating to conventions of portraying the Shoah, often leaving his readers unhinged. Not least because of his postmodern approach, the readers are confronted with a new and different picture of the Shoah. Instead of assuming the perspective of a chronicler or a suffering victim, Lind opts for employing various ways of representation and attitudes, such as including the perspective of a child or using a picaresque depiction. Furthermore, the author shows that after the terrible events everything has changed. Values and Actions once regarded as grotesque have suddenly become the norm and are now considered as ordinary in a world that has been turned upside down.