1. Transcriptional control of neuronal cell fates in the developing spinal cord
The dorsal horn of the spinal cord is an integrative center that transmits and processes diverse somatosensory information. The neurons in the dorsal spinal cord can be grouped into excitatory and inhibitory neurons that use glutamate and GABA/glycine as their fast transmitters, respectively. Diversity of dorsal horn neurons is also indicated by the restricted expression of peptides in distinct subpopulations. We have found that several transcription factors play important roles in determining the acquisition of transmitter phenotypes, the expression of transmitter and peptide receptors, and dorsal horn laminae III/IV neurons in the developing dorsal spinal cord.
2. Conversion of astrocytes into functional neurons in vitro and in vivo
Many transcription factors and chromatin-modifying processes play important roles in controlling the stability of the differentiated cellular identity. However, studies of induced pluripotent stem cells (iPSCs) demonstrated that differentiated cells are not irreversibly locked in their mature identity and can be de-differentiated by overexpression of selective transcription factors. More findings that defined transcription factors can directly convert fibroblasts and glial cells to functional neurons further demonstrate the feasibility of direct reprogramming of non-neuronal cells directly into neurons. During the past several years, we have found that a single transcription factor Ascl1 can efficiently convert postnatal astrocytes from mouse dorsal midbrain, into functional, synapse-forming neurons in vitro. Moreover, we have that Ascl1 alone can induce astrocyte-to-neuron conversion in the dorsal midbrain, cortex, and striatum in vivo.
Ongoing projects in the laboratory include:
(1) By analyzing the phenotypes of knockout mice, we are interested in studying how transcription factors control neurotransmitter phenotypes in developing spinal cord.
(2) Conversion of astrocytes and fibroblasts into diverse neuronal cell types, including glutamatergic neurons, GABAergic neurons, motor neurons, cholinergic neurons, dopaminergic neurons, serotonergic neurons, and noradrenergic neurons.
(3) Investigating whether the induced neurons have similar properties with that of the target neurons and whether they can be used for neuronal repair in the injured nervous system.