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. 2023 Oct 7;31(12):3545–3563. doi: 10.1016/j.ymthe.2023.10.003

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© 2023 The Author(s)

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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EM studies revealed that the host tissue makes synaptic contacts with hNSCs in zQ175 mice within the implantation site

(A) hNSC/ diaminobenzidine (DAB)-labeled nerve terminal (L-NT) making a symmetrical synaptic contact (single white arrow) with an hNSC/DAB-labeled dendrite (L-DEND). vGlut1-L-NT (vGlut1 NT) making an asymmetrical synaptic contact with the head of a stubby spine that contains a perforated postsynaptic density (two white arrows pointing to synaptic contact). The vGlut1 NT (purple arrowheads pointing to VIP labeling) is distinguished from the adjacent nerve terminal (which is only DAB labeled). The primary origin of vGlut1-containing neurons is the cortex. (B) An unlabeled nerve terminal (U-NT) making an asymmetrical synaptic contact (arrow) with an underlying hNSC-positive labeled dendrite (L-DEND) (note the darkened DAB reaction product within the dendrite). The U-NT might originate from either the host striatum, thalamus, or cortex (see A), while the labeled dendrite originates from the implanted stem cells. (C) A U-NT is making an asymmetrical synaptic contact (arrow) with an underlying hNSC-positive/labeled dendritic spine (L-SP) (note the darkened DAB reaction product within the spine). As in (B), the U-NT might originate from either the host striatum, thalamus or cortex (see A), while the labeled dendritic spine originates from the implanted stem cells. (D) An L-NT is making an asymmetrical synaptic contact (arrow) with an underlying hNSC-positive/labeled dendrite (L-DEND) (note the darkened DAB reaction product within the nerve terminal and dendrite). The L-NT and dendrite originate from the implanted stem cells. (E) An L-NT is making an asymmetrical synaptic contact (arrow) with an underlying hNSC-positive/L-SP (note the darkened DAB reaction product within the nerve terminal and spine). The L-NT and spine originate from the implanted stem cells. (F) An L-NT is making a symmetrical synaptic contact (arrow) with an underlying hNSC-positive/L-DEND (note the darkened DAB reaction product within the nerve terminal and dendrite). The L-NT and dendrite originate from the implanted stem cells.