The Mammalian Cell Fate Map

Mar 18th, 2009 | By | Category: Embryonic Stem Cell Research

As a part of writing up my PhD thesis, I adapted this figure from Gilbert’s Developmental Biology, Fourth Edition:
gilberts-dev-adapted1
(This figure is my own. Click for a much larger version–suitable for printing on an 8.5×11 sheet of paper.)

When I write about embryonic stem cells, I’m often saying something like this:

Making a new mammal requires a single cell to become hundreds of distinct cell types–each with a unique pattern of gene expression that is maintained throughout life.

The answer is tremendously complex–much deeper and interesting than “sperm meets egg.” Part of what’s going on in that first trimester is the establishment of all those hundreds of cell types. Complex three-dimensional geometry, a dozen or so of delicate signals, precise timing and luck itself all play into this process. It often fails–in a lab dish or in the gestation of a baby.

This figure lays out, to a rough approximation, our understanding of the various paths a differentiating cell can go down–step-wise–to reach all of those hundreds of cell types found in an adult. Start at the top, at a zygote (a fertilized egg). Trace your way through to all of the organ systems and tissues in the body. Embryonic stem cells, a kind of pluripotent stem cell derived from inner cell mass cells, act like they’re near the top of this tree; that is their utility.

The arrows are somewhat deceptive. Each of the branch points is a moment of chance. The developing fetus stacks the deck, but it’s still a game of cards. The arrows are more probabilities; they should look like Feynman diagrams, not such beautifully deterministic paths. (That’s the answer to the Jeopardy question ‘how can this figure be more complicated and daunting?’)

Any one of these steps can, and do, go wrong–and whole branches can be omitted by accident–rendering the development a failure.

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