To be or not to be a stem cell: Sanford-Burnham lab finds new mechanism

Chemical modification of genetic material (RNA, shown here) helps keep stem cells in their “ground state”, study finds

The year is a mere 14 days old and yet my colleagues have already blogged here about very positive news regarding CIRM-funded stem cell-based clinical trial projects for treating heart disease and sickle cell anemia. At times like these, it’s good to take a step back and keep in mind that these projects didn’t materialize overnight. Instead, they began with basic research that helped pave the road to the clinic.

And the steady drum of basic stem cell research keeps beating in 2014. Just last week Dr. Crystal Zhao’s lab at the Sanford-Burnham Medical Research Institute reported in Nature Cell Biology that they’ve identified a new molecular mechanism that helps keep embryonic stem cells in their stem cell state rather than maturing into specialized cell types. The lead author, Dr. Yang Wang, is a CIRM Research Training scholar.

Now don’t let the word “basic” in basic research fool you. This laboratory work is incredibly intricate requiring deep understanding, insightful thinking, and years of plugging away at fundamental questions of the inner workings of cells. The Sanford-Burnham team focused on the unique fork-in-the-road decision that each embryonic stem cell can make based on cues from its environment: (1) do I make copies of myself and maintain the ability to become any cell type (scientists call this pluripotency: pluri = many; potent = powerful)? or (2) do I mature into a specialized cell type like a heart muscle or liver cell?

Zhao’s lab zeroed in on two specific enzymes within the cell, called methylases, which decorate the cells’ genetic material with chemical tags. The team showed that these methylases could tag the genetic code that’s responsible for maturing a stem cell into a specialized cell type. It turns out that when this chemical tagging occurs the genetic material becomes unstable and degrades and so the stem cell maintains its “ground state” and doesn’t mature. The team demonstrated this property using some genetic engineering tactics: the team depleted the two methylases from the cell. Now, with no chemical tagging, the genetic material remained stable and was able to drive the cells towards a mature cell type.

Like a lot of basic research, the application of this discovery to a stem cell therapy may not jump out at you. Still, by clearly understanding the molecular basis for what makes a stem cell maintain its “stemness”, scientists can develop more consistent batches of stem cells that could be used for manufacturing stem cell-based therapies for a wider and wider patient population. As Dr. Wang points out:

Embryonic stem cells … have great potential in therapeutic application but how stem cells maintain pluripotency is still largely unknown. To understand the mechanisms for keeping stem cells in a ground state is important for establishing systematical standards of stem cells, leading to advanced methods for expanding stem cells and generating new protocols to [mature] stem cells. 

So while we celebrate the recent clinical trial updates here in 2014, the basic research also being done today may help keep the stem cell party thriving in 2024 and beyond.

CIRM Funding: Research Training II (TG2-01162) 

Todd Dubnicoff

New face brings fresh perspective to stem cell agency Board

Joe Panetta: photo by K.C. Alfred, San Diego Union Tribune

You can never have too much help in making good decisions, that’s why we are delighted to welcome Joe Panetta as the newest member of our governing Board, the Independent Citizens Oversight Committee.

Joe has just been appointed to the Board by Governor Jerry Brown and he brings with him a wealth of experience that is going to be invaluable to us. Not only is he the President and CEO of Biocom – the association for the southern California life sciences community – but he’s also worked at the Environmental Protection Agency (EPA) and has many years leading biotech companies.

It’s just the kind of experience we need on our Board to help guide us as we try to choose the best science and help move it as fast as we can to patients.

Joe says “I sincerely look forward to serving on the ICOC where I can work with my fellow committee members, researchers and members of the great California life sciences industry to move the promise of stem cell technology from research into development and commercialization. Above all, I am excited to be a member of an institution that is leading the way in developing cures for patients in California and ultimately around the world.”

We couldn’t have said it better. Joe takes over the seat left empty by the death of Duane Roth last year. Like Duane, Joe is heavily involved with biotech in San Diego, including being a member of the Board of CONNECT, which links inventors and entrepreneurs with the resources they need for success.

Our Chairman, Jonathan Thomas, welcomed the news saying: “Joe’s experience, expertise and long career in biotech and government will be invaluable in helping us choose the most promising science. He brings a new voice and a fresh perspective and those can only make our Board even more effective.”

Fresh perspective? I’ll say. In his spare time Joe has been known to run a 3 hours 39 minute marathon, zip line in Costa Rica and dive to 650 feet in a nuclear submarine.

kevin mccormack