Vascularized human cortical organoids (vOrganoids) model cortical development in vivo

Yingchao Shi, Le Sun, Mengdi Wang, Jianwei Liu, Suijuan Zhong, Rui Li, Peng Li, Lijie Guo, Ai Fang, Ruiguo Chen, Woo Ping Ge, Qian Wu, Xiaoqun Wang

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Modeling the processes of neuronal progenitor proliferation and differentiation to produce mature cortical neuron subtypes is essential for the study of human brain development and the search for potential cell therapies. We demonstrated a novel paradigm for the generation of vascularized organoids (vOrganoids) consisting of typical human cortical cell types and a vascular structure for over 200 days as a vascularized and functional brain organoid model. The observation of spontaneous excitatory postsynaptic currents (sEPSCs), spontaneous inhibitory postsynaptic currents (sIPSCs), and bidirectional electrical transmission indicated the presence of chemical and electrical synapses in vOrganoids. More importantly, singlecell RNA-sequencing analysis illustrated that vOrganoids exhibited robust neurogenesis and that cells of vOrganoids differentially expressed genes (DEGs) related to blood vessel morphogenesis. The transplantation of vOrganoids into the mouse S1 cortex resulted in the construction of functional human-mouse blood vessels in the grafts that promoted cell survival in the grafts. This vOrganoid culture method could not only serve as a model to study human cortical development and explore brain disease pathology but also provide potential prospects for new cell therapies for nervous system disorders and injury.

Original languageEnglish (US)
Article numbere3000705
JournalPLoS biology
Volume18
Issue number5
DOIs
StatePublished - May 2020

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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