Fate Mapping via Ms4a3-Expression History Traces Monocyte-Derived Cells
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Abstract
Most tissue-resident macrophage (RTM) populations are seeded by waves of embryonic hematopoiesis and are self-maintained independently of a bone marrow contribution during adulthood. A proportion of RTMs, however, is constantly replaced by blood monocytes, and their functions compared to embryonic RTMs remain unclear. The kinetics and extent of the contribution of circulating monocytes to RTM replacement during homeostasis, inflammation, and disease are highly debated. Here, we identified Ms4a3 as a specific gene expressed by granulocyte-monocyte progenitors (GMPs) and subsequently generated Ms4a3 TdT reporter, Ms4a3 Cre, and Ms4a3 CreERT2 fate-mapping models. These models traced efficiently monocytes and granulocytes, but no lymphocytes or tissue dendritic cells. Using these models, we precisely quantified the contribution of monocytes to the RTM pool during homeostasis and inflammation. The unambiguous identification of monocyte-derived cells will permit future studies of their function under any condition.
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Clonal hematopoiesis (CH) prominently involves variants of epigenetic regulatory genes, such as DNMT3A and TET2.
“CH prominently involves variants of epigenetic regulatory genes, such as DNMT3A and TET2, which constitute an increased risk for hematologic malignancies, cardiovascular events and stroke 34,45,70,71 .”
From Clonal hematopoiesis-associated motoric deficits caused by monocyte-derived microglia accumulating in aging mice (2025) · cites this paper as [45]
The Introduction (p. 4) describes Ms4a3-based tracing of monocyte progenitors, not clonal hematopoiesis. Searches for DNMT3A, TET2, epigenetic regulators, and clonal hematopoiesis found no passage in our copy addressing the attributed claim. (LLM, conf=0.75)
Experimental — accuracy not yet measuredCH variants such as DNMT3A and TET2 constitute an increased risk for hematologic malignancies, cardiovascular events and stroke.
“CH prominently involves variants of epigenetic regulatory genes, such as DNMT3A and TET2, which constitute an increased risk for hematologic malignancies, cardiovascular events and stroke 34,45,70,71 .”
From Clonal hematopoiesis-associated motoric deficits caused by monocyte-derived microglia accumulating in aging mice (2025) · cites this paper as [45]
The Introduction (p. 4) describes an Ms4a3 fate-mapping model, and the Discussion (pp. 15–16) addresses MS4A3 expression and cell-cycle regulation. Searches for DNMT3A, TET2, clonal hematopoiesis, cardiovascular risk, and stroke found no passage in our copy addressing the claimed disease risks. (LLM, conf=0.76)
Experimental — accuracy not yet measured
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- Authors
- Liu, Z., Gu, Y., Chakarov, S., Bleriot, C., Kwok, I., Chen, X., Shin, A., Huang, W., Dress, R. J., Dutertre, C.-A., Schlitzer, A., Chen, J., Ng, L. G., Wang, H., Liu, Z., Su, B., & Ginhoux, F.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Agency for Science, Technology and Research (SG)
- University of Bonn (DE)
- Corresponding author
- Su, Bing
- Ginhoux, Florent
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2019-09
- Volume
- 178
- Issue
- 6
- Pages
- 1509-1525.e19
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2971790873
- Cited by
- 719
- References
- 12
- Citations by year
- 2026: 102 · 2025: 143 · 2024: 113 · 2023: 97 · 2022: 94 · 2021: 88 · 2020: 72 · 2019: 9
- FWCI
- 26.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- Agency for Science, Technology and Research
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- monocyte-derived cells, tissue-resident macrophages, CFU-GM, fate mapping, embryonic hematopoiesis, macrophage homeostasis, inflammation, granulocytes
- MeSH terms
- Animals, Granulocytes, Hematopoiesis, Homeostasis, Inflammation, Macrophages, Membrane Proteins, Monocytes, Gene Expression, Cell Cycle Proteins, Mice, Granulocyte-Macrophage Progenitor Cells
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