The birth and death of stem cells

Jeremy Gunawardena suggested that it would be appropriate to write about one of Ernest McCulloch’s papers, given the news that he passed away last week.  McCulloch, together with James Till, was responsible for the original demonstration that stem cells actually exist.  He was 84 when he died, two weeks short of the 50th anniversary of the publication of his most famous paper (Till and McCulloch, 1961, Radiation Research A direct measurement of the radiation sensitivity of normal mouse bone marrow cells 14, 213).  McCulloch was a physician and Till a biophysicist, and together they did the kind of experimentally-driven quantitative modeling that we today consider to be super-modern.  [I wonder if there’s a fashion cycle in science as well as in clothes, and if so whether they’re synchronized?  If one could predict based on the fashionability of, say, Markov models in biology that miniskirts would be making a comeback in the next few years… well, actually I can’t think why that would be interesting or useful, so never mind.]

Jeremy, who is more familiar with the dusty areas of the library stacks than most, suggested a fractionally more recent paper for today’s post: Till, J.E., McCulloch, E.A. and Siminovitch, L. 1963, A stochastic model of stem cell proliferation, based on the growth of spleen colony-forming cells.  Proc. Natl. Acad Sci. USA 51 29-36.

IBM 7090. Image from http://www.computer-history.info.

Take a look at the title — see what I mean?  You’d expect that title to be attached to an article published in this century, not the last one.  It gets better.  The authors are trying to understand single-cell behavior (and infer the behavior of populations), using Markov processes and Monte Carlo simulations, painstakingly performed on an IBM 7090 computer. I’ve given up trying to get people interested in when systems biology started, but if I hadn’t this would certainly be a contender in the systems biology ancestry stakes.

Equal rights for (stem cell) daughters

I’ve been thinking about writing about these papers for a while, but Nature just beat me to it.*  (I am definitely behind on my posting!)  A smidgen of information to encourage you to read more: when people talk about how stem cells manage to divide indefinitely, they usually argue that there is some kind of asymmetric division in which the stem-cell-ness of the stem cell stays with one daughter, which can then continue to divide in perpetuity.  The other daughter is marked for differentiation and (eventual) death.  Two experimental groups (Douglas  Winton‘s lab and Hans Clevers‘ lab) collaborated with a team of  theorists (Allon Klein and Ben Simons) and came up with what looks like strong evidence that, in the context of intestinal stem cells, this cannot be true.  Instead, it appears both daughters have equal stem cell potential; which has significant consequences for the way we thought stem cell numbers were controlled.  Take a look.  I think you’ll enjoy it.

* Oh.  And so did Developmental Cell.