Journal
STEM CELL REPORTS
Volume 10, Issue 2, Pages 390-405Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2017.12.012
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Funding
- Oregon National Primate Research Center [OD11092]
- California Institute for Regenerative Medicine (CIRM) [TB1-01183]
- CIRM [RB5-07320]
- NIH [NS085097]
- Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA
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Cellular replacement therapies for neurological conditions use human embryonic stem cell (hESC)- or induced pluripotent stem cell (hiPSC)-derived neurons to replace damaged or diseased populations of neurons. For the spinal cord, significant progress has been made generating the in-vitro-derived motor neurons required to restore coordinated movement. However, there is as yet no protocol to generate in-vitro-derived sensory interneurons (INs), which permit perception of the environment. Here, we report on the development of a directed differentiation protocol to derive sensory INs for both hESCs and hiPSCs. Two developmentally relevant factors, retinoic acid in combination with bone morphogenetic protein 4, can be used to generate three classes of sensory INs: the proprioceptive dI1s, the dI2s, and mechanosensory dI3s. Critical to this protocol is the competence state of the neural progenitors, which changes over time. This protocol will facilitate developing cellular replacement therapies to reestablish sensory connections in injured patients.
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