Session 2, Abstract 12

DERIVING SENSORY SPINAL INTERNEURONS FROM HUMAN PLURIPOTENT STEM CELLS

Samantha Hain*1, Daniel Sivalingam1, Sandeep Gupta1 and Lorenzo del Castillo1 (Samantha J Butler1, 2), University of California, Los Angeles, Dept. of Neurobiology, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, 405 Hilgard Ave, Los Angeles, CA 90095. 

Spinal sensory interneurons (INs) integrate and relay somatosensory information, such as the experience of touch or pain. The loss of somatosensation after injury or disease can be debilitating both physically and emotionally. One means of restoring sensory function is to repopulate diseased or damaged areas of the nervous system with stem-cell derived sensory INs. We are working towards this goal by developing directed differentiation protocols based on the mechanisms that specify sensory INs during spinal cord development. Sensory INs arise as a result of signaling from the Bone Morphogenetic Proteins (BMPs) family of growth factors. BMPs pattern the dorsal spinal cord, including the progressive production of roof plate (RP) cells at the dorsal midline, and the dI1 and dI3 populations of sensory INs, which mediate proprioception and mechanosensation respectively. As a first step, we have determined the culture conditions in which BMPs can induce dorsal spinal IN fates from mouse embryonic stem cells (mESCs). We have shown that BMP4 and BMP6 specifically direct mESCs toward different dorsal identities: BMP4 is most effective at directing mESCs into dI1s and dI3s, whereas BMP6 allows for efficient differentiation into RP cells. As a second step, we are now assessing whether these BMPs can similarly direct human stem cells towards dorsal spinal fates. The successful implementation of these protocols will permit us to work towards the ultimate goal of restoring sensory function using patient specific INs generated in vitro.

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