It seems all that was needed for human stem cells to maintain their pluripotent state, was just a little transcriptional rewiring. This cellular circuitry wasn’t handled by a master electrician though, but rather a group of Cambridge area researchers.
A collaboration involving the Babraham Institute, Cambridge Stem Cell Institute and the European Bioinformatics Institute, led by Dr Gabriella Ficz, Professor Wolf Reik and their colleagues, published results demonstrating that human stem cells can be reverted back to a base state, losing characteristics that mark them as a specific cell lineage and regaining the unrestricted potential (pluripotency) to develop into any cell type.
Current human pluripotent stem cells lack the transcription factor circuitry that regulates the ground state of mouse embryonic stem cells (ESC), the scientists found that short-term expression of two components, NANOG and KLF2, is sufficient to ignite other elements of the network and reset the human pluripotent state. Here are some of the highlights from the project:
- Transcription factor circuitry is rewired in human pluripotent stem cells
- Transcriptome and metabolism are similar to mouse ground-state embryonic stem cells
- Genome-wide hypomethylation in reset cells indicates global epigenetic erasure
- Reset human cells can incorporate into mouse preimplantation epiblast
Author Dr Gabriella Ficz, commented: “This study brings us one step closer to the ultimate aim in regenerative medicine of using patient-derived cells to avoid immune rejection in cell and organ replacement therapies. It’s all about finding out what the cell needs in order to survive and multiply while making sure that they have lost the memory of the tissue they came from. Both conditions need to be fulfilled for successful use of embryonic stem cells in tissue generation.”
Professor Wolf Reik, who oversaw the work, added: “We can liken this reprogramming to giving cells amnesia so they forget any previous developmental decisions they have made. Returning them to this state means that we can then control their cellular decisions, allowing us to generate the particular types of cells needed. This area has huge medical potential, for example, being able to provide reset stem cells back to a patient that we can be confident will develop into the correct cell type as required, for example, nerve cells.”
Find out more about stem cells and pluripotency in Cell, September 2014.