학술논문

Deriving Dorsal Spinal Sensory Interneurons from Human Pluripotent Stem Cells
Document Type
article
Source
Stem Cell Reports. 10(2)
Subject
Biochemistry and Cell Biology
Biological Sciences
Regenerative Medicine
Neurosciences
Physical Injury - Accidents and Adverse Effects
Stem Cell Research - Nonembryonic - Human
Stem Cell Research - Induced Pluripotent Stem Cell
Stem Cell Research
Stem Cell Research - Induced Pluripotent Stem Cell - Human
Stem Cell Research - Embryonic - Non-Human
Neurodegenerative
Stem Cell Research - Embryonic - Human
Spinal Cord Injury
Development of treatments and therapeutic interventions
5.2 Cellular and gene therapies
Neurological
Bone Morphogenetic Protein 4
Cell Culture Techniques
Cell Differentiation
Human Embryonic Stem Cells
Humans
Induced Pluripotent Stem Cells
Interneurons
Sensory Receptor Cells
Spinal Cord
Tretinoin
directed differentiation
human embryonic stem cells
induced pluripotent stem cells
mechanosensation
mouse spinal cord
neurons
primate spinal cord
proprioception
sensory interneurons
spinal cord
Clinical Sciences
Biochemistry and cell biology
Language
Abstract
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.