Chimeric brain models to study human glial-neuronal and macroglial-microglial interactions
Summary
Chimeric brain models generated by transplanting human pluripotent stem cell (hPSC)-derived neural cells are valuable for studying the development and function of human neural cells in vivo. To explore glial-neuronal and glial-glial interactions, we co-engraft hPSC-derived primitive neural progenitor cells and primitive macrophage progenitors into neonatal mouse brains, generating chimeric brains containing human microglia, macroglia, and neurons. Using super-resolution imaging and 3D reconstruction, we observe human microglia pruning synapses and engulfing neurons. Single-cell RNA sequencing reveals human glial progenitor populations and dynamic stages of astroglial development resembling those in the human brain. Cell-cell communication analysis identifies strong human neural interactions, including NRXN-NLGN3 signaling between neurons and astrocytes and SPP1- and PTN-MK-mediated communication between microglia and astroglia. This co-transplantation model provides a powerful approach to study complex human glial-neuronal interactions and mechanisms underlying neurological diseases. Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.
| Authors | Jin M, Ma Z, Zhang H, Dang R, Papetti AV, Stillitano AC, Zou L, Goldman SA, Jiang P |
|---|---|
| Journal | Cell reports |
| Publication Date | 2026 Jan 27;45(1):116794 |
| PubMed | 41499239 |
| PubMed Central | PMC12974579 |
| DOI | 10.1016/j.celrep.2025.116794 |