Genetic analysis of healthy blood samples
The lifelong formation of blood cells requires continuous self-renewal of the hematopoietic stem cell (HSC) pool, and functional differentiation programs. This is guaranteed by asymmetric cell division of HSC that give rise to HSC and progenitors which then produce daughter cells restricted to specific lineages and terminally differentiated cells of myeloid and lymphoid lineages. Chromatin dynamics drive developmental processes and our aim is to study chromatin dynamics during blood cell differentiation. We expect to unravel important genetic programs needed for normal blood cell differentiation. For this, we will isolate mature blood cells (B- and T-lymphocytes, monocytes, NK cells, granulocytes) and assess proteins that play an important role in chromatin dynamics, for example Lamin proteins which are intermediate filament proteins that form a meshwork on the nucleoplasmic side of the nuclear envelope. Three genes are known to encode Lamin A/C and B in human somatic cells; B-type lamins are essential for cell survival, while A-type lamins are normally only expressed in differentiated cells. Various studies indicate that Lamin proteins have functions in nuclear envelope assembly, envelope size, and integrity and are involved in DNA replication, chromatin organization and gene regulation. Moreover, recent reports have shown that Lamin A/C bind specific chromatin regions in lineage cells, which seems to be important to define cell fate. The exact role of Lamin proteins during healthy blood development is incompletely understood. We will i) use ChIP-Seq analysis followed by high throughput sequencing, ii) identify transcriptional networks during blood development by performing FAIRE- and DNAse-Seq. The role of identified TFs will be further assessed by knockdown, overexpression and ChIP-Seq analysis to define whether and how they are important to drive blood development.
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Tidspunkt for anonymisering og sletting av dataene
- Anonymisering: januar 2015
- Sletting: desember 2019