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Izpisua Belmonte garners international attention for string of major discoveries

Salk professor Juan Carlos Izpisua Belmonte and his research team received worldwide media attention earlier this year for a string of groundbreaking discoveries reported in top science journals.

The papers, which shed light on fundamental problems in aging, mitochondrial disease and regenerative medicine, were covered in TIME magazine, The Washington Post, Scientific American, New Scientist and The Guardian, to name just a few.

The first of the discoveries to be announced was published April 23 in Cell. In that paper, the scientists reported a new method of preventing the transmission of mitochondrial diseases in mice using gene-editing technologies.

For thousands of women around the globe carrying a mitochondrial disease, having a healthy child can be a gamble. This set of diseases affect mitochondria, tiny powerhouses that generate energy in the body’ s cells and are passed exclusively from mother to child.

A novel type of human stem cell is shown in green integrating into the surrounding cells of a nonviable mouse embryo. The stem cell holds promise for one day growing replacement functional cells and tissues.

Women wishing to prevent their children from inheriting mitochondrial diseases have typically relied on preimplantation genetic diagnosis to pick the healthiest embryos, but that is no guarantee of having a healthy baby. In a mouse study, Izpisua Belmonte’s lab developed a simple technique to eliminate mitochondrial mutations from eggs or early embryos, which has the potential to prevent babies from inheriting mitochondrial diseases.

“Currently, there are no treatments for mitochondrial diseases,” says Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory and holder of the Roger Guillemin Chair. “Our technology may offer new hope for mitochondrial disease carriers.”

In the second study, detailed later the same month in Science, the lab focused on Werner syndrome, a genetic disorder that causes people to age more rapidly than normal. People with the disorder suffer age-related diseases early in life, including cataracts, type 2 diabetes, hardening of the arteries, osteoporosis and cancer, and most die in their late 40s or early 50s.

By studying Werner syndrome, the team found that the aging process for humans is tied to the deterioration of tightly packaged bundles of cellular DNA. The discovery could eventually lead to methods of preventing and treating age-related diseases such as cancer, diabetes and Alzheimer’s.

From left: Juan Carlos Izpisua Belmonte, Alejandro Ocampo and Pradeep Reddy

In early May, the team reported in Nature the discovery of a novel type of pluripotent stem cell–cells capable of developing into any type of tissue–whose identity is tied to their location in a developing embryo. This contrasts with stem cells traditionally used in scientific study, which are characterized by their time-related stage of development.

The researchers dubbed this new class of cells “region-selective pluripotent stem cells,” or rsPSCs for short. The rsPSCs were easier to grow in the laboratory than conventional human pluripotent stem cells and offered advantages for large-scale production and gene editing (altering a cell’s DNA), both desirable features for cell replacement therapies.

Collaborating with the labs of Salk Professors Joseph Ecker and Alan Saghatelian, the Izpisua Belmonte team performed extensive characterization of the new cells and found rsPSCs showed distinct molecular and metabolic characteristics as well as novel epigenetic signatures– patterns of chemical modifications to DNA that control which genes are turned on or off without changing the DNA sequence.

Juan Carlos Izpisua Belmonte and Jun Wu

“The region-selective state of these stem cells is entirely novel for laboratory-cultured stem cells and offers important insight into how human stem cells might be differentiated into derivatives that give rise to a wide range of tissues and organs,” says Jun Wu, a postdoctoral researcher in Izpisua Belmonte’s lab and first author of the Nature paper. “Not only do we need to consider the timing, but also the spatial characteristics of the stem cells. Understanding both aspects of a stem cell’s identity could be crucial to generating functional and mature cell types for regenerative medicine.”