Project details

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The regulation of stem cell decisions in developing and ageing tissues.

Keywords:
development Stem cell division zebrafish

Researchers:
Dr. J.T.M.L. Paridaen

Nature of the research:
Using vertebrate model systems (zebrafish, mouse) and cell culture to understand the molecular and cell biological mechanisms that underlie stem cell decision-making.

Fields of study:
cell biology Stamcelbiologie molecular biology

Background / introduction
Stem cells act in developing and adult organisms to produce the proper number of specialized cells in the body. When stem cells divide, they select a particular division mode that is symmetric or asymmetric. This division mode determines how many specialized and stem cell daughter cells are generated per stem cell division. As stem cells directly affect the future of the organism, it is essential that they choose a division mode that is appropriate for development, maintenance and repair of tissues. Defective division mode selection is implicated in developmental disorders, diseases such as cancer, and ageing.
Research question / problem definition
When making decisions on division mode and cell fates, stem cell integrate cell-intrinsic and -extrinsic signals and factors. Although several of these signals and factors have been identified, it is not clear how and when a stem cell selects its division mode and daughter cell fates. Furthermore, it is not clear how the history of stem cells, such as the inheritance of certain fate-influencing factors or particular RNA transcripts, affects their decisions during each consecutive division.
Workplan
In our lab, we aim to understand how single stem cells make decisions on division mode and cell fates, and how these decisions affect developing and adult tissues. We focus on the role of heritable factors such as subcellular structures, complexes and organelles and how the (a)symmetrical segregation of these factors during division of the mother stem cell affects its mode of division and fate specification of its daughter cells. We employ single cell analyses, lineage tracing techniques and computational modeling to look at single stem cell behaviour in the developing and adult brain. We use the zebrafish and mouse as our main model systems. In particular, we are interested in the role of fate-determining factors such as signalling pathways and subcellular structures in symmetric and asymmetric stem cell divisions.

The student will participate in the lab routine, analyze and discuss the obtained data, and write a scientific report. The student will work in close collaboration with the young PI. The detailed workplan will be determined and discussed together with the student. Possible techniques include zebrafish and mouse embryology, genome-editing and transgenesis of zebrafish embryos, molecular biology, cell culture, live imaging of zebrafish embryos/mouse tissues/cultured cells, and single-cell analysis (e.g. RNAseq).
The proposed research project will be performed within the new European Research Institute for the Biology of Ageing (ERIBA), a research institute focusing on cellular and molecular aspects of ageing.
References
1. Paridaen JTML and Huttner WB. (2014). Neurogenesis during development of the vertebrate central nervous system. EMBO reports.
2. Paridaen JTML, Wilsch-Bräuninger M, Huttner WB. (2013) Asymmetric inheritance of centrosome-associated primary cilium membrane directs ciliogenesis after cell division. Cell.
3. Wilsch-Bräuninger M, Peters J, Paridaen JTML, Huttner WB. (2011) Basolateral rather than apical primary cilia on neuroepithelial cells committed to delamination. Development.
4. Paridaen JTML, Janson E, Utami KH, Pereboom TC, Essers PB, van Rooijen C, Zivkovic D, MacInnes AW. (2011) The nucleolar GTP-binding proteins Gnl2 and nucleostemin are required for retinal neurogenesis in developing zebrafish. Dev Biol.
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