Stem Cells and Chromatin Team
Team Leader: Dr Tomoyuki Sawado
Location: Brookes-Lawley Building, Sutton
Section: Section of Haemato-Oncology
In multicellular organisms, the earliest stem cells give rise to intermediate and more mature cells (differentiation) and simultaneously divide to renew the early stem cell pool (self-renewal). At each step of the differentiation/self-renewal cycle, cells undergo a binary decision to either commit and differentiate into the next stage or to maintain their original status.
The fundamental nature of the differentiation process is the expression of different subsets of genes in different cell types. Among 35,000 human genes, only small subpopulations are expressed in differentiated cells. The “choice” of what kind of genes are expressed or silenced in a specific lineage is determined by combinatorial actions of transcription factors on gene-specific cis-regulatory elements, such as enhancers, silencers, and locus control regions (LCRs). Once a particular expression status is established, it is epigenetically maintained through DNA replication and cell divisions (epigenetic inheritance).
click to enlarge | We ask three questions about epigenetic inheritance in the context of cellular differentiation:
1) Is the epigenetic status of a non-replicated allele always faithfully propagated to daughter alleles after DNA replication? |
2) Are there instances when epigenetic states are NOT faithfully propagated? In other words, can epigenetic states become asymmetric between replicated sister alleles?
3) What are the levels of fidelity of epigenetic inheritance in stem cells, differentiated cells, and tumour cells?
In the Section of Haemato-Oncology
