Single-cell transcriptomics reveals reversible microglia/macrophage activation after human retinal neuron transplantation into mouse retina
Abstract
Host retinal microglia and macrophages can limit donor neuron survival and integration after transplantation, but the cellular mechanisms underlying this response remain unclear. In this study, we used human embryonic stem cell-derived retinal ganglion cells, generated from Brn3b-tdTomato-Thy1.2-derived retinal organoids, and transplanted them subretinally into healthy adult CX3CR1GFP mice. Three days later, GFP-positive host myeloid cells were isolated by fluorescent activated cell sorting and profiled using 10× single-cell RNA sequencing, with immunohistochemistry validating spatial and molecular changes. Transcriptomic and RNA velocity analyses revealed a microglia/macrophage activation continuum, including homeostatic, transitory, proliferative, and activated states. Transplantation induced a disease-associated microglia-like program, marked by reduced Tmem119 and increased Apoe, Lgals3, Spp1, Cybb, and related activation genes. Integrated atlas comparisons linked this response to retinal and neurodegenerative disease-associated myeloid states. Importantly, separate homeostatic-to-activated and activated-to-homeostatic trajectories suggest that transplantation-induced host myeloid activation is dynamic and partially reversible, with implications for improving future retinal cell therapies.
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BibTeX
@article{kriukov2026singlecell,
title = {{Single-cell transcriptomics reveals reversible microglia/macrophage activation after human retinal neuron transplantation into mouse retina}},
author = {Emil Kriukov and Anthony Mukwaya and Paul Francis Cullen and Hio Tong Kam and George Baldwin and Volha V. Malechka and Nasrin Refaian and Nikita Bagaev and Everett Labrecque and Sthavir Vinjamuri and Dong Feng Chen and Milica A. Margeta and Petr Baranov},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117232},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)02610-6},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Single-cell transcriptomics reveals reversible microglia/macrophage activation after human retinal neuron transplantation into mouse retina
AU - Emil Kriukov
AU - Anthony Mukwaya
AU - Paul Francis Cullen
AU - Hio Tong Kam
AU - George Baldwin
AU - Volha V. Malechka
AU - Nasrin Refaian
AU - Nikita Bagaev
AU - Everett Labrecque
AU - Sthavir Vinjamuri
AU - Dong Feng Chen
AU - Milica A. Margeta
AU - Petr Baranov
PY - 2026
DA - 2026/10/21
JO - iScience
DO - 10.1016/j.isci.2026.117232
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)02610-6
AB - Host retinal microglia and macrophages can limit donor neuron survival and integration after transplantation, but the cellular mechanisms underlying this response remain unclear. In this study, we used human embryonic stem cell-derived retinal ganglion cells, generated from Brn3b-tdTomato-Thy1.2-derived retinal organoids, and transplanted them subretinally into healthy adult CX3CR1GFP mice. Three days later, GFP-positive host myeloid cells were isolated by fluorescent activated cell sorting and profiled using 10× single-cell RNA sequencing, with immunohistochemistry validating spatial and molecular changes. Transcriptomic and RNA velocity analyses revealed a microglia/macrophage activation continuum, including homeostatic, transitory, proliferative, and activated states. Transplantation induced a disease-associated microglia-like program, marked by reduced Tmem119 and increased Apoe, Lgals3, Spp1, Cybb, and related activation genes. Integrated atlas comparisons linked this response to retinal and neurodegenerative disease-associated myeloid states. Importantly, separate homeostatic-to-activated and activated-to-homeostatic trajectories suggest that transplantation-induced host myeloid activation is dynamic and partially reversible, with implications for improving future retinal cell therapies.
SN - 2589-0042
ER -