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Development of a chimeric model to study and manipulate human microglia in vivo


Hasselmann et al., 2019. Neuron.

View the article here or download a preprint of the article here

Experiment Design:
Environments
Microglia from multiple environments including freshly isolated human microglia (ExVivo, n=17 patients), xMGs (3 iHPC cell lines, n=3-6 mice per line, 13 mice total), iMGLs (n=6 wells), and cultured human microglia (InVitro, n=13 patients) from our lab and Chris Glass’ lab (UCSD; Gosselin et al., (2017) An environment-dependent transcriptional network specifies human microglia identity), were transcriptomically compared. xMG-transplanted mice were aged to 2-6 months depending on cell line.

In vivo LPS
MITRG mice transplanted with xMGs (cell line: AICS-0036) were aged to 2 months then administered 3 injections of LPS (n=5; 2mg/kg; 1 injection/24 hours) or saline (n=3). Mice were euthanized 12 hours after the final injection and RNA was collected for seq.

In vitro LPS
Day 38 iMGLs were plated at 200,000 cells/well on a Matrigel-coated (1mg/well) 24-well-plate containing 2mL of medium. Cells were then treated with either LPS (100ng/mL) or DPBS and incubated for 24 hours at 37°C before lysis for RNA isolation (n=3 wells per treatment group).

If you find this data useful for your work, we would appreciate it if you would cite:

Hasselmann, J., Coburn, M. A., England, W., Figueroa Velez, D. X., Kiani Shabestari, S., Tu, C. H., . . . Blurton-Jones, M. (2019). Development of a Chimeric Model to Study and Manipulate Human Microglia In Vivo. Neuron. doi:10.1016/j.neuron.2019.07.002

The datasets included in the plots can be downloaded at:
MBJ iMGL, xMG, and ExVivo
GEO accession number GSE133432

Gosselin InVitro and ExVivo
NCBI dbGaP, accession number phs001373.v1.p1

MBJ InVitro
GEO accession number GSE89189


Please feel free to contact Mathew Blurton-Jones (mblurton@uci.edu) or Jonathan Hasselmann (jhasselm@uci.edu) with any questions.