The development of a complex multicellular organism from a single-cell zygote into a complete animal (or plant) is somewhat of a neat trick. It’s impressive that from the zygote perhaps a couple hundred different types of cells can emerge, with each of the trillions of final cells at the right time and place. What’s just as surprising is that the whole process is so neatly programmed by evolution into an organism’s genome that it happens automatically as the appropriate set of genes gets turned on at just the right time.
Developmental biologists have been studying the process for decades. What they’ve found is that cells at any particular stage not only make up specific types of embryonic tissue, but are also programmed to turn on genes for the next generation of cells based on the types of tissue and nearby tissue they occur in.
Biologists have now learned enough about the details of this program that they can make it work – for certain tissues and organs – in a lab dish instead of a complete embro, starting from pluripotent stem cells.
In research just published, the organ was a mouse pituitary gland, a very small organ, but with complex function. In humans it’s about the size of a pea and weighs only half a gram. But it secretes dozens of different endocrine hormones.
It’s particularly important that the gland has a 3-dimensional structure that’s essential to its function. Being able to grow a pituitary gland from stem cells is a very significant achievement towards eventual regenerative medicine, in which larger and more complex organs such as kidneys or even hearts can be grown from stem cells.
The possibility that functional, three-dimensional tissues and organs may be derived from pluripotent cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), represents one of the grand challenges of stem cell research, but is also one of the fundamental goals of the emerging field of regenerative medicine. Developmental biology has played a central role in informing such efforts, as it has been shown that stem cell differentiation can be directed to follow a given lineage pathway by culturing stem cells in conditions that recapitulate the specific cellular and molecular environment from which such cells normally emerge during embryogenesis. Intriguingly, recent work has shown that when ES cells are cultured under the appropriate conditions, they can be driven to self-organize into complex, three-dimensional tissue-like structures that closely resemble their physiological counterparts, a remarkable advance for the field.
New work by Hidetaka Suga of the Division of Human Stem Cell Technology, Yoshiki Sasai, Group Director of the Laboratory for Organogenesis and Neurogenesis, and others has unlocked the most recent achievement in self-organized tissue differentiation, steering mouse ESCs to give rise to tissue closely resembling the hormone-secreting component of the pituitary, known as the adenohypophysis, in vitro.
Not only did the lab-grown pituitary tissue have much of the appropriate physiological activity, but when transplanted into mice whose pituitary gland had been removed, the mice survived much better than controls.