Interspecies chimerism with human embryonic stem cells generates functional human dopamine neurons at low efficiency
STEM CELL REPORTS(2024)
摘要
Interspecies chimeras offer great potential for regenerative medicine and the creation of human disease models. Whether human pluripotent stem cell-derived neurons in an interspecies chimera can differentiate into functional neurons and integrate into host neural circuity is not known. Here, we show, using Engrailed 1 (En1) as a development niche, that human naive -like embryonic stem cells (ESCs) can incorporate into embryonic and adult mouse brains. Human -derived neurons including tyrosine hydroxylase (TH)+ neurons integrate into the mouse brain at low efficiency. These TH+ neurons have electrophysiologic properties consistent with their human origin. In addition, these human -derived neurons in the mouse brain accumulate pathologic phosphorylated a-synuclein in response to a-synuclein preformed fibrils. Optimization of human/mouse chimeras could be used to study human neuronal differentiation and human brain disorders.
更多查看译文
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要