RT Journal Article
SR Electronic
T1 Vascularized human cortical organoids model cortical development in vivo
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 682104
DO 10.1101/682104
A1 Yingchao Shi
A1 Le Sun
A1 Jianwei Liu
A1 Suijuan Zhong
A1 Mengdi Wang
A1 Rui Li
A1 Peng Li
A1 Lijie Guo
A1 Ai Fang
A1 Ruiguo Chen
A1 Woo-Ping Ge
A1 Qian Wu
A1 Xiaoqun Wang
YR 2019
UL http://biorxiv.org/content/early/2019/06/26/682104.abstract
AB Modelling the neuronal progenitor proliferation and organization processes that produce mature cortical neuron subtypes is essential for the study of human brain development and the search for potential cell therapies. To provide a vascularized and functional model of brain organoids, we demonstrated a new paradigm to generate vascularized organoids that consist of typical human cortical cell types and recapitulate the lamination of the neocortex with a vascular structure formation for over 200 days. In addition, the observation of the sEPSCs (spontaneous Excitatory Postsynaptic Potential) and sIPSCs (spontaneous Inhibitory Postsynaptic Potential) and the bidirectional electrical transmission indicated the presence of chemical and electrical synapses in the vOrganoids. More importantly, the single-cell RNA-seq analysis illustrated that the vOrganoids exhibited microenvironments to promote neurogenesis and neuronal maturation that resembled in vivo processes. The transplantation of the vOrganoids to the mouse S1 cortex showed human-mouse co-constructed functional blood vessels in the grafts that could promote the survival and integration of the transplanted cells to the host. This vOrganoid culture method could not only serve as a model to study human cortical development and to explore brain disease pathology but could also provide potential prospects for new cell therapies for neural system disorders and injury.