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Self-organized pituitary-like tissue from mouse ES cells
Date:11/14/2011

d the first tantalizing insights into the developmental capacity of pluripotent stem cells, showing their ability to give rise to multi-cell-type populations of cortical and retinal neurons that spontaneously self-organize into stratified tissue nearly identical to that of the developing embryo.

In the group's most recent work, Suga sought to use SFEBq to derive the secretory component of the pituitary (hypophysis) from mouse ES cells. In embryonic development, the pituitary emerges from a region of the non-neural (rostral) head ectoderm, adjacent to the anterior neural plate. Guided by molecular interactions, this placodal region forms an indentation, known as Rathke's pouch, in the developmental predecessor of the roof of the mouth, and eventually gives rise to the anterior section of the pituitary, the source of hormones involved in growth, reproduction and modulating the physiological response to stress.

The Sasai lab had previously reported how a modified version of the SFEBq approach lacking extrinsic growth factors could spur ES cells to give rise to hypothalamic neurons. Building on this finding, Suga found by further tweaking the conditions he could steer populations of such stem cells to differentiate simultaneously into the neighboring rostral head ectoderm and hypothalamic neuroectoderm, both of which are required to development of the adenohypophysis. Interestingly, the cells in these clusters spontaneously organized into distinct layers resembling those of the corresponding embryonic tissues. This effect appears to be attributable to the increase of BMP signaling in larger cell aggregates, leading to differentiation into non-neural ectoderm. To test whether co-culture of this ectoderm with hypothalamic tissue would lead to the formation of Rathke's pouch-like structures, Suga observed the ESC-derived aggregates for nearly two weeks, and found that by adding the signaling factor Sonic hedgehog, he was able to induce the self-directed
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Contact: Douglas Sipp
sipp@cdb.riken.jp
RIKEN
Source:Eurekalert

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