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Cellf-Deception: Human microglia clone 3 (HMC3) cells exhibit more astrocyte-like than microglia-like gene expression

Rahm, K. K.; Kinghorn, B. S.; Moody, M. J.; Stone, B. C.; Strong, K. C.; Hansen, D. V.; Bailey, M. H.

2025-08-06 neuroscience
10.1101/2025.08.04.665415 bioRxiv
Show abstract

Recent advances in Alzheimers research suggest that the brains immune system plays a critical role in the development and progression of this devastating disease. Microglial cells are vital as immune cells in the brains defense system. Human Microglia Clone 3 (HMC3) is a cell line developed as a promising experimental model to understand the role of microglial cells in human diseases including Alzheimers and other neurodegenerative diseases. The frequency of HMC3 cell usage has increased in recent years, with the idea that this cell line could serve as a convenient model for human microglial cell functions. Here, we utilize gene-pair ratios from pseudo-bulk and scRNAseq expression data to create predictive models of cell-type origins. Our model reveals that the HMC3 cell line represents various cells, with the highest cell similarity score relating to astrocytes, not microglia. These findings suggest that the HMC3 cell line is not a reliable human microglia model and that extreme caution should be taken when interpreting the results of studies using the HMC3 cell line.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.