The Cold Spring Harbor Symposium this year explored how stem cells are regulated. Five days, over 450 scientists and manuscript editors, and me. I’m drowning in acronyms, my brain is bursting, but I can’t wait for more. Philadelphia, here I come!

Below is my outsider’s notion of trends based on this meeting and two days of visiting scientists in the Big Apple. (It’s a closed meeting, soI’ve included only generalities. I may be able to go back over this in a couple weeks and get more specific)

Here’s the take-home:

There are more niches than we thought, more cell types than we thought, they are regulated in more ways than we thought, and we shouldn’t have been surprised.

Here are more specifics:

The environment can’t be overlooked. Stem-cell biologists are gaining an appreciation of architecture, niche architecture. Slides depicting old versions of the niche showed newer, more nuanced versions of how stem cells’ environments were structured, how niches are first made, then seeded. From a practical perspective, there was broader appreciation, and discussion that future therapies won’t just need to prepare cells but prepare the environment that receives them. A damaged heart or brain must be ready to accept new cardiomyocytes or neurons.

Assays matter. A shift in detection techniques may reveal that those supposedly very rare cells may be less rare after all.

It takes all sorts of stem cells. The diversity of stem cells and progenitors may have been greatly under-estimated. The sheer number of types of stem cells described in the poster session would have left few tissues out of an anatomy text book, but it’s still an open question how often healing relies on stem cells or more mature types. Time and again talks described how a population of stem cells thought to yield a plethora of types is actually several pools of flexible cells, each giving rise to a narrower range of progeny. The diversity of cell types seemed to apply functionally, spatially, and temporally. Even within the same tissue, stem cell types seem to switch over time, depending on different cues for activation.

There are many, many controls over cell fate. Talks revealed new members in pluripotency, differentiation, and maintenance networks. These act through a stack of levels involving chromatin to transcription machinery plus several sorts of regulatory RNAs. Finding a piece of the puzzle is a scientific accomplishment; fitting that piece into a whole is not yet possible. Stem-cell biologists want tools and techniques from systems biologists, and even then, they know the whole picture is incomplete because it lacks dynamics. Stem-cell biologists are getting ready for the movie.

The cell-type landscape is very furrowed and might even be flexible. Perhaps the most common image at the conference was a 50-year old artwork depicting a marble poised to run downhill into one of a few valleys. In Waddington’s epigenetic landscape, the marbles that reach the lowest levels represent cells that have taken on a final identity (i.e. terminally differentiated cells). Shallow depressions poised above the valleys represent tissue specific stem cells. Embryonic stem cells are poised at the top of the hills. Reprogramming techniques move marbles uphill. Talks at this conference identified gravity-defying techniques to roll marbles uphill, plus a landscape that might be more rugged but also more navigable than was once believed.

Toward the end of the conference, I had started classifying talks.. That way, even if I couldn’t remember what HUH1.1 stood for, I didn’t feel completely lost. The most common type slots individual components into networks. Many conclusion slides exclaimed triumphantly “X targets Y in cell Z under conditions of W”

Perhaps the next most common type of talk identified or characterized cell types. “Cell A makes molecules B,C, and D but not E”. This was often, but still too infrequently, followed by “Cell A does action Y in environment Z.”

I thought it odd that I recognized only one scientist from the FDA’s meeting on how to decide whether ES-derived therapies could be shown safe enough for clinical trials. That entire discussion centered on stem cells’ unpredictability, and the theme of this Symposium was how stem cells are controlled and regulated. Seems like these groups would have something to say to each other.

Finally, a word on Cold Spring Harbor. The attendees were younger, more diverse, and (of course) more international than attendees at the FDA meeting. While the talks covered wide tracts of ground in little space, the conversations were geeky and mellow. Scientists discussed each other’s talks as a form of entertainment, the way Lost or Battlestar Galactica fans might dissect a particularly well-executed episode and have fun guessing what should come next. And that usually in a context of sunshine, flowering shrubs, and, often enough, alcoholic beverages.

I want to thank those scientists who let me shadow or sit by them during presentations and put up with my constant questions “What’s BLMP2? GBM? Hess2? Why not try ROSA?). You know you are. Thanks.