March issue cover: What’s going on here?

March

Alamy photo “Talus cones on Svalbard”

March is already winding to a close, but we wanted to take a quick break to answer that most burning of all questions: what is going on with our cover this month?

On p.331 of this month’s issue, Owen Rackham and colleagues describe an algorithm called Mogrify that predicts transcription factor combinations for direct reprogramming between 173 human cell types and 134 tissues (see also the News and Views by Patrick Cahan).

Mogrify effectively paints a landscape of cell conversions and provides directions for getting from one point to another. This is often visualized using a variation on Waddington’s epigenetic landscape (for example, see “A deterministic map of Waddington’s epigenetic landscape for cell fate specification” by Bhattacharya et al.).

Visualization of Waddington's epigenetic landscape

Visualization of Waddington’s epigenetic landscape{credit}Bhattacharya et al. BMC Syst Biol. 2011; 5: 85.{/credit}

The epigentic landscape as imagined by Waddington involves a marble (the cell) rolling down a hill with many alternate paths (cell fates).

You can imagine the image on the cover (depicting talus deposits on the surface of a mountain in Norway) as the epigenetic landscape, with the different cell fates rising out of the pluripotent state. In this case, there is no marble, because the cell and its fate (address on the landscape) are in fact the same thing. But similar to the talus cones, the cell’s fate is not unchangeable. As Mogrify makes clear, the cell has the potential to transform into many different cell types, regardless of its current address on the landscape. We just have to understand the map to help it get there.

Other articles related to Mogrify:

Breakthrough in human cell transformation could revolutionise regenerative medicine (University of Bristol press release)

Serendipity’s touch on cell conversions (Duke-NUS)

Highlights from the Keystone Symposium on Stem Cells & Reprogramming

View from the Resort at Squaw Creek. Not a bad place for a conference!

View from the Resort at Squaw Creek. Not a bad place for a conference!{credit}Brooke LaFlamme{/credit}

I recently attended the joint Keystone Symposium “Stem Cells & Reprogramming” and “Engineering Cell Fate & Function” at the beautiful Resort at Squaw Creek. In addition to gorgeous weather, there was an amazing lineup of talks demonstrating the power and promise of stem cells and cell/tissue engineering. Here are just a few of the highlights from the meetings:

Keynote: Optogenetics

Karl Deisseroth from Stanford University kicked off the joint meeting with an overview of his lab’s research in optogenetics and how they’ve used the technology both to control and map neuronal networks in live animals or intact tissues. The Deisseroth lab has used optogenetics to better understand the neuronal architecture and genetic structure underlying complex behaviors, such as those associated with anxiety. In his talk, Prof. Deisseroth outlined how they are using optogenetic tools to target neuronal wiring using Boolean-like genetic systems to identify neurons expressing specific combinations of markers.

The second part of his talk focused on CLARITY, a method developed in the Deisseroth lab to allow for 3D imaging of neurons in intact tissues or whole brains. You can see some of the amazing videos generated with this technique here.

To learn more, you can find a list of Deisseroth lab publications here.

Stem cells and reprogramming in human disease modeling and treatment

There were a ton of talks (and posters) demonstrating the utility of stem cells and directed differentiation for human disease modeling and treatment development. I’ll only mention a few here, but all the talks were excellent. Continue reading