SRY potentially regulates early dopaminergic differentiation from male hiPSCs
Other conference paper


摘要SRY, the sex-determining gene, was found to co-localize with Tyrosine Hydroxylase (TH) positive neurons in male rat substantia nigra and in postmortem male human brains. Knockdown of SRY in male rats caused motor dysfunction making it a candidate capable of exerting male-specific effects on brain sexual dimorphism. However, it is unknown if SRY is a gene that affects neurodevelopmental process. To answer this question, we utilized human induced pluripotent stem cells (hiPSCs) to establish an in vitro dopaminergic (DA) neuron differentiation system. We also generated stable male hiPSC line with ectopic activation of SRY. Our results showed that endogenous SRY was upregulated during the early DA neuron differentiation stage. When we ectopically overexpressed SRY during early differentiation, several neuron progenitor markers were upregulated which indicated a possible enhancing role of SRY in early DA neuron differentiation. Further evidence showed that FOXA1/FOXA2, two important transcription factors in DA neuron development, were upregulated significantly after SRY overexpression. In the future, knockout of SRY will be performed to examine if early DA neuron differentiation was inhibited. Furthermore, RNA-seq of neuron progenitor samples will be used to examine global gene expression under different SRY expression status. Subsequently, CHIP-seq will be used to identify the targets bound by SRY. We hope, through our study, we can understand better the regulatory function of SRY in male-specific neurogenic process.
著者Cao DD, Law WN, Chan WY
關鍵詞SRY, sexual dimorphism, dopaminergic neuron differentiation

上次更新時間 2018-22-01 於 09:18