Adhesion to the bone marrow niche - podosome-like structures in hematopoietic stem cells

Downloadstatistik des Dokuments (Auswertung nach COUNTER):

Frommer, Miriam: Adhesion of bone marrow niche - podosome-like structures in hematopoietic stem cells. Hannover : Gottfried Wilhlem Leibniz Universität, Diss., 2024, xiii, 150 S., DOI: https://doi.org/10.15488/17238

Zeitraum, für den die Download-Zahlen angezeigt werden:

Jahr: 
Monat: 

Summe der Downloads: 81




Kleine Vorschau
Zusammenfassung: 
Maintenance and homeostasis of the hematopoietic system is enabled by hematopoietic stem and progenitor cells (HSPC). These multipotent cells ensure the replenishment of all hematopoietic cells by giving rise to progeny with the ability to differentiate into respective cells while also self-renewing themselves. A crucial factor to regulate this essential feature of HSPC is their interaction with a specific microenvironment – the hematopoietic stem cell niche in the bone marrow (BM). The interaction of HSPC with their niche provides the signals necessary for the cells to maintain their stemness and to sustain the HSPC population. In order to provide these signals constantly, adhesion of the stem cells to the extracellular matrix (ECM) of the BM niche is of the utmost importance. Yet, the way in which HSPC anchor to their specific microenvironment is not well understood. In the here presented work, the adhesion structures established by HSPC upon contact with fibronectin are investigated in regard to their appearance, maturity state and composition of cell adhesion molecules (CAM).By investigating the spatial distribution of native and mature adhesion structure markers alongside the actin cytoskeleton in adherent HSPC using super resolution microscopy it was found, that HSPC adhere in a dynamic manner and display varying morphologies that can contain protrusions and/or structures resembling podosomes. Further investigation of these podosome-like structures (PLS) revealed that these structures are defined by an F-actin spot strongly co-localizing with phosphorylated PYK2 (pPYK2). Assessment of the spatial distribution of pPYK2, alongside the classic podosome proteins vinculin and paxillin, showed a distribution of these molecules towards the periphery of the F-actin spot. This distribution pattern became more pronounced - resembling classic podosomes more - in cells with round morphology and increased number of PLS. Additionally, examining the differentiation state of HSPC with different morphologies, it was found that the round, PLS containing cells were less differentiated compared to cells with deviating observed morphologies.Together, these findings indicate a highly dynamic adhesion behavior of HSPC, involving PLS. Given the importance of proper stem cell retention in the BM niche environment, for full function of the hematopoietic system, understanding the adhesion processes involved is an essential step in gaining insight into hematopoiesis in health and disease.
Lizenzbestimmungen: CC BY-NC 3.0 DE
Publikationstyp: DoctoralThesis
Publikationsstatus: acceptedVersion
Erstveröffentlichung: 2024
Die Publikation erscheint in Sammlung(en):Naturwissenschaftliche Fakultät
Dissertationen

Verteilung der Downloads über den gewählten Zeitraum:

Herkunft der Downloads nach Ländern:

Pos. Land Downloads
Anzahl Proz.
1 image of flag of Germany Germany 35 43,21%
2 image of flag of United States United States 22 27,16%
3 image of flag of Netherlands Netherlands 3 3,70%
4 image of flag of India India 3 3,70%
5 image of flag of Israel Israel 3 3,70%
6 image of flag of United Kingdom United Kingdom 3 3,70%
7 image of flag of Australia Australia 3 3,70%
8 image of flag of France France 2 2,47%
9 image of flag of China China 2 2,47%
10 image of flag of Canada Canada 2 2,47%
    andere 3 3,70%

Weitere Download-Zahlen und Ranglisten:


Hinweis

Zur Erhebung der Downloadstatistiken kommen entsprechend dem „COUNTER Code of Practice for e-Resources“ international anerkannte Regeln und Normen zur Anwendung. COUNTER ist eine internationale Non-Profit-Organisation, in der Bibliotheksverbände, Datenbankanbieter und Verlage gemeinsam an Standards zur Erhebung, Speicherung und Verarbeitung von Nutzungsdaten elektronischer Ressourcen arbeiten, welche so Objektivität und Vergleichbarkeit gewährleisten sollen. Es werden hierbei ausschließlich Zugriffe auf die entsprechenden Volltexte ausgewertet, keine Aufrufe der Website an sich.