# Cellf-deception: human microglia clone 3 (HMC3) cells exhibit more astrocyte-like than microglia-like gene expression

**Authors:** Kylee K. Rahm, Branden S. Kinghorn, Myanna J. Moody, Ben C. Stone, Kenton C. Strong, Brian S. Kim, Yen Jou Chang, Samantha N. Sleight, Alyssa A. Nitz, David V. Hansen, Matthew H. Bailey

PMC · DOI: 10.3389/fbinf.2025.1681811 · Frontiers in Bioinformatics · 2025-11-04

## TL;DR

This study shows that HMC3 cells, thought to model microglia, actually resemble astrocytes more, raising concerns about their use in Alzheimer's research.

## Contribution

The study reveals that HMC3 cells are not reliable as a human microglia model due to their astrocyte-like gene expression.

## Key findings

- HMC3 cells show higher similarity to astrocytes than microglia based on gene expression.
- Predictive models using gene-pair ratios indicate HMC3 cells represent multiple cell types.
- The findings question the validity of using HMC3 cells for studying microglial functions.

## Abstract

Recent advances in Alzheimer’s research suggest that the brain’s immune system plays a critical role in the development and progression of this devastating disease. Microglial cells are vital as immune cells in the brain’s 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 Alzheimer’s 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.

We utilized gene-pair ratios from bulk and single-cell RNA sequencing (scRNA-seq) expression data to create predictive models of cell-type origins.

Our model reveals that the HMC3 cell line represents various cell types, 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.

## Full-text entities

- **Diseases:** Alzheimer's (MESH:D000544), neurodegenerative diseases (MESH:D019636)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** HMC3 — Homo sapiens (Human), Transformed cell line (CVCL_II76)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12623408/full.md

## References

60 references — full list in the complete paper: https://tomesphere.com/paper/PMC12623408/full.md

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Source: https://tomesphere.com/paper/PMC12623408