An integrated view of mammalian embryonic differentiation
- Reference number
- I06-0248
- Start and end dates
- 070901-101231
- Amount granted
- 3 000 000 SEK
- Administrative organization
- Karolinska Institutet
- Research area
- Life Science Technology
Summary
Studies on embryonic stem (ES) cells have important implications for both basic research and human medicine, e.g. in regenerative medicine. The long-term objectives of this research programme it to gain a better understanding of the molecular nature of self-renewal and differentiation in the context of early embryonic differentiation. We specifically propose to develop and apply high-resolution array- and sequence-based techniques to profile the transcriptome of undifferentiated ES cells and early progenitors in mouse and human. High-resolution transcriptome profiling techniques measures the expression level of all known transcribed regions to enable the estimation of transcript isoforms for both protein- and non-coding genes. In order to also study the in vivo embryonic differentiation we would develop a protocol that allows amplification of RNA species from a single-cell to again be analyzed using high-resolution profiling. We would ultimately like to integrate publicly available data sets on epigenetics, transcription, post-transcription and translation in ES cells to study how the different levels of gene regulation are coordinated to define self-renewal and early embryonic differentiation. By comparing the data from in vitro model systems with in vivo cell data we would like to identify similarities and discrepancies that could guide the future development of differentiation protocols used to in vitro differentiate ES cell lines to improve human medicine.