ORIGINAL RESEARCH article
Front. Bioinform.
Sec. Genomic Analysis
Volume 5 - 2025 | doi: 10.3389/fbinf.2025.1681811
Cellf-Deception: Human microglia clone 3 (HMC3) cells exhibit more astrocyte-like than microglia-like gene expression
Provisionally accepted
Kylee K. Rahm1Brandon S. Kinghorn2Myanna J. Moody2Kenton C. Strong3Brian S Kim2
David V. Hansen4
Matthew H. Bailey2*- 1Brigham Young University Department of Microbiology and Molecular Biology, Provo, United States
- 2Brigham Young University Department of Biology, Provo, United States
- 3Brigham Young University Department of Computer Science, Provo, United States
- 4Brigham Young University Department of Chemistry and Biochemistry, Provo, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
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. Here, we utilize gene-pair ratios from pseudo-bulk and scRNA-seq 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.
Keywords: HMC3 cells, iPSC-derived microglia (iMG), Microglia, Astrocytes, Cell-type classification, Alzheimer's disease, iMG cells
Received: 11 Aug 2025; Accepted: 14 Oct 2025.
Copyright: © 2025 Rahm, Kinghorn, Moody, Strong, Kim, Hansen and Bailey. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Matthew H. Bailey, matthew.bailey@byu.edu
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.