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Making induced pluripotent stem cells a loopy process, say Stanford/VA researchers

Interesting stem cell news today. A blog post from the California Institute for Regenerative Medicine describes research published in Cell Stem Cell by researchers at Stanford and the VA Palo Alto Health Care System. The study investigates the relative difficulty reprogramming adult cells from fully developed tissues like skin into what are known as induced pluripotent stem cells, or iPS cells. The technique was first described in 2006 by Nobel Prize recipient Shinya Yamanaka, MD, PhD (now at the Gladstone Institutes in San Francisco). As the blog post describes:

And yet seven years after the initial breakthrough, reprogramming is still very inefficient: less than 99 percent of treated cells actually get reprogrammed into embryonic-like stem cells. Many researchers are trying to better understand what goes on inside cells during the reprogramming process to help increase this efficiency and ultimately help accelerate disease research.

The researchers, including CIRM grant recipient Ji-Fan Hu, MD, PhD, and Stanford endocrinologist Andrew Hoffman, MD, found that chromosomal looping is a critical step in reprogramming. And not all would-be-iPS cells do it. From CIRM's blog post:

During the reprogramming process, scientists activate a handful of genes that act as master control switches: they produce proteins that bind to specific spots on the cell’s DNA. This DNA binding then activates a cascading set of genes that ultimately re-sets the skin cells’ properties to the stem cell-like state of iPSC. It turns out that those cascading events only happen if the string-like DNA loops around, bringing proteins bound to distant parts of the DNA together (see the simplified illustration above).

Hu and his colleagues showed that those loops were only present in the cells that did get reprogrammed. The other 99% that don’t get reprogrammed into stem cells lacked the DNA loops.

Previously: Nobel Prize-netting iPS-cell discovery was initially a tough sell (for me, anyway) and The end of iPS? Stanford scientists directly convert mouse skin cells to neural precursors

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