Stem Cells Know How to Unwind
News May 03, 2016
This insight provides new avenues for improving the quality and stability of embryonic stem cells – an essential requirement to fulfill their promise in regenerative medicine.
How our DNA is stored and packaged in the nucleus can be viewed as two different states: regions of the genome that are ‘open for business’ and can be actively read, and regions that are locked away by being tightly packed and inaccessible to the factors that read DNA.
The researchers looked in detail at the mysterious tightly packed portions of the genome, called constitutive heterochromatin. Previous research has shown that heterochromatin is maintained in an unusually open and uncompacted organisation in embryonic stem cells, which is different to all other cell types. It is thought that this rare form of genome architecture may contribute to keeping stem cells in an unspecialised state, still full of the potential to become any cell type in the body. Why heterochromatin is organised in this way in embryonic stem cells has previously been unknown.
As described in the journal Genes & Development, the researchers identified a new pathway controlling heterochromatin organisation in mouse embryonic stem cells. Unexpectedly, this pathway assigns new roles for several well-known stem cell factors. The research showed that the stem cell factors, Nanog and Sall1, bind to heterochromatin and help to maintain this portion of the genome in an open form. Embryonic stem cells lacking Nanog and Sall1 showed major defects in heterochromatin organisation, including the closure and compaction of the chromatin. These new findings uncover the first direct connection between stem cell factors and the control of genome architecture, and explains why stem cell heterochromatin is normally in an open and uncompacted form. Loss of heterochromatin regulation has potential consequences for the long-term genetic stability of stem cells, and the ability of stem cells to mature into specialised cell types.
Dr Peter Rugg-Gunn, senior author on the research paper and research group leader at the Babraham Institute explained: “This unanticipated connection between stem cell factors and heterochromatin organisation is important because it tells us about how stem cells work. By tapping into this newly identified connection, we open up new avenues for more successful reprogramming of adult cells to a stem cell state, which is a priority for future regenerative medicine approaches.”
‘Incompatible’ Donor Stem Cells Cure Adult Sickle Cell PatientsNews
Doctors at the University of Illinois Hospital have cured seven adult patients of sickle cell disease, an inherited blood disorder primarily affecting the black community, using stem cells from donors previously thought to be incompatible, thanks to a new transplant treatment protocol.READ MORE
Non-Coding DNA Variants Increase Autism RiskNews
Whilst the contribution of gene variants to autism risk is well-established, the contribution of the 98% of the genome that does not code for gene sequences is still relatively unknown. Now, a new study has identified regulatory elements as potential genetic risk factors.READ MORE