Jian Feng and his colleagues have overcome a key obstacle to converting skin cells into dopamine neurons, and their method could change the way scientists work with all cells.
Cell Conversion Breakthrough Could Benefit Parkinson’s Patients
Published January 7, 2016 This content is archived.
story based on news release by ellen goldbaum
A team of investigators led by Jian Feng, PhD, professor in the Department of Physiology and Biophysics, has developed a new way to ramp up the conversion of skin cells into dopamine neurons — research that could help patients with Parkinson’s disease.
Published in Nature Communications, their method is the fastest and most efficient yet developed.
The best of the other methods produces 5 percent dopamine neurons in about two weeks; theirs produces 60 percent in 10 days.
Potential for Mending Faulty Neurons
Feng and his collaborators have proven that the converted neurons are functional mid-brain dopaminergic neurons, the type lost in Parkinson’s disease.
Their finding enables researchers to generate patient-specific neurons that could be transplanted into the brain to repair faulty neurons. It can also be used to efficiently screen new treatments for Parkinson’s disease.
Gatekeeper Protein Key to Reprogramming Fibroblasts
The researchers overcame a major obstacle to cellular conversions with the discovery that the transcription factor p53 acts as a gatekeeper protein.
“We found that p53 tries to maintain the status quo in a cell, guarding against changes from one cell type to another,” Feng explains.
“Once we lowered the expression of p53, things got interesting: We were able to reprogram the fibroblasts into neurons much more easily.”
The advance has importance to basic cell biology, Feng says.
“This is a generic way for us to change cells from one type to another. It proves that we can treat the cell as a software system when we remove the barriers to change.
“If we can identify transcription factor combinations that control which genes are turned on and off, we can change how the genome is being read. We might be able to play with the system more quickly, and we might be able to generate tissues similar to those in the body — even brain tissue.”
Timing Essential in Converting Skin Cells
The key to successfully converting the cells was timing. Feng and his colleagues found that the cell is receptive to change just before it tries to sense its environment to ensure readiness for genome duplication.
By lowering p53 at that point, they could easily turn the skin cells into dopamine neurons, with transcription factor combinations discovered in previous studies. These manipulations turn on the expression of Tet1, a DNA modification enzyme that changes how the genome is read.
Collaborators from UB, Harvard, China
The researchers’ paper is titled “Cell Cycle and p53 Gate the Direct Conversion of Human Fibroblasts to Dopaminergic Neurons.”
Feng is senior author; the lead author is Houbo Jiang, PhD, research scientist in physiology and biophysics. Other authors from that department include Zhen Yan, PhD, professor.
Collaborators also come from:
- the UB Center for Computational Research
- the UB School of Pharmacy and Pharmaceutical Sciences
- Harvard Medical School
- Capital Medical University (Beijing)
- Ruijin Hospital (Shanghai)