PEPSTEM · Effect of neuropeptides on selective neuronal differentiation of mouseembryonic stem cells
FP7 — People (Marie Curie Actions)
- Duration
- 2012-05-21 → 2015-05-20
- EU contribution
- €45,000
- Participants
- 1
- Scheme
- MC-ERG
Lines connect the coordinator with its partners.
Results in brief
Effect of neuropeptides on selective neuronal differentiation of mouse embryonic stem cells
The scientific aim of the current project was to investigate the effect of different neuropeptides on the differentiation of pluripotent stem cells in culture in a three-dimensional (3D) structure, the 'minibrain'. In this project, we planned to investigate which are the most efficient neuropeptides that can promote mouse ESCs, iPSCs and human iPSCs to selectively differentiate into certain neuron-types. In the currently running Marie Curie (MC) Industrie-Academia Partnerships and Pathways (IAPP) project STEMCAM BioTalentum (BIO) is producing iPSCs both from mouse and human. These cell-lines were also planned to be used in PEPSTEM. We were going to test neuropeptides that are available at the market to minimise the costs, but modified neuropeptides planned to be involved as well if our results suggest. We also planned to test the synaptical connections at a morphologic level, and other neuronal properties of the differentiated cells in electrophysiological levels, like Ca-signalling. We expected to find new ways of selective differentiation of ESCs/iPSCs into neurons, and to get novel information on pathways and transcriptional networks that regulate differentiation. The information generated by these studies will contribute to stem cell therapy and modern regenerative medicine.
Data: CORDIS, © European Union
Project objective
The capacity of embryonic stem cells (ES cells) to differentiate into neuronal cells represents a potential source for neuronal replacement and a model for studying factors controlling early stages of neuronal differentiation. Various molecules have been used to induce such differentiation but so far neuropeptides acting via G-protein coupled receptors have not yet been profoundly investigated. Since undifferentiated ES-cells express numerous G-coupled receptors which expression is increasing with time in culture, it suggest a prominent role of these receptors in the maintenance and development of ES cells. RT-PCR analyses of Ghrelin is proven to have a prominent effect on the growth and proliferation of the neural progenitor cells in the dorsal motor nucleus of the vagus (DMNV), but its effect on ES cells has not yet been investigated. MC4 receptor, which binds both alpha-MSH and AgRP is expressed by ES-cells but wheter it has a function on neuronal differentiation is unknown. Y1 and Y5 receptors of NPY have proven to have a significant role in maintaining the pluripotency of ES cells. These original data demonstrate that functional G-protein coupled receptors have a role on differentiation into a neuronal phenotype. It opens an exciting new field for neuropeptide regulation of tissue ontogenesis. Using a three-dimensional „minibrain” could reveal potential selective differentiation in the forming tissue. Since these neuropeptides often regulates each other’s expression in the adult brain, it would be interesting to see whether these regulation networks can form in vitro in a differentiating cell-culture. This would open new ways of studying the effect of neuropeptides on neural differentiation and synaptic network formation.
Original text from CORDIS.
Participants
- BIOTALENTUM TUDASFEJLESZTO KFT · GoedoelloCoordinatorHungary
Links
Data: CORDIS, © European Union