A CD4-lineage erythro–myeloid progenitor within the adult bone marrow defines an alternative pathway for macrophage generation
9 affiliations
- 1Department of Dermatology, Medical University of Vienna, Vienna, Austria
- 2Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales Australia
- 3Sydney Medical School, The University of Sydney, Sydney, Australia
- 4Research Division of Infection Biology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
- 5School of Biomedical Sciences, University of New South Wales, Sydney, New South Wales Australia
- 6Department of Chemical and Biomolecular Engineering, Materials Characterization and Fabrication Platform, University of Melbourne, Melbourne, Victoria Australia
- 7School of Medical Sciences, University of Sydney, Sydney, New South Wales Australia
- 8University of Sydney Nano Institute, University of Sydney, Sydney, New South Wales Australia
- 9Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel
Abstract
Tissue-resident macrophages originate from distinct developmental sources, but their adult replenishment is thought to depend exclusively on circulating monocytes. Here we identify a previously unrecognized CD4-lineage erythro–myeloid progenitor (EMPROR) in the adult bone marrow that provides an alternative pathway for macrophage generation. EMPROR cells are phenotypically and transcriptionally distinct from hematopoietic stem cells, common myeloid progenitors and monocyte precursors, lacking Csf1r and Ccr2 while expressing Cd4 and Kit. Single-cell RNA sequencing, RNA velocity analysis and lineage assays reveal macrophage, neutrophil, megakaryocytic and erythroid potential. EMPROR cells generate perivascular and tumor-associated macrophages independently of CCR2-mediated monocyte recruitment and contribute to erythroid and granulocytic lineages under inflammatory and neoplastic conditions. Transcriptomic comparisons position EMPROR cells closest to embryonic erythro–myeloid progenitors, indicating the persistence of an embryonic-like program in adult bone marrow. These findings reveal an alternative pathway of adult myelopoiesis that sustains macrophage diversity beyond the classical monocyte lineage.
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BibTeX
@article{tikoo2026cd4lineage,
title = {{A CD4-lineage erythro–myeloid progenitor within the adult bone marrow defines an alternative pathway for macrophage generation}},
author = {Shweta Tikoo and Rohit Jain and Brendon Martinez and Renhua Song and Matthias Wielscher and Carlos Márquez-Burgoa and Anastasiya Hladik and Simone Rizzetto and Lisa E. Shaw and Minoo Ghannadan and Stephanie A. Gerhofer and Andrew J. Mitchell and Maria Elizabeth Torres-Pacheco and Fabio Luciani and Matthias Farlik and Justin J. L. Wong and Sylvia Knapp and Philipp Starkl and Stuart T. Fraser and Steffen Jung and Wolfgang Weninger},
journal = {Nature Immunology},
year = {2026},
month = oct,
doi = {10.1038/s41590-026-02686-1},
url = {https://doi.org/10.1038/s41590-026-02686-1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A CD4-lineage erythro–myeloid progenitor within the adult bone marrow defines an alternative pathway for macrophage generation
AU - Shweta Tikoo
AU - Rohit Jain
AU - Brendon Martinez
AU - Renhua Song
AU - Matthias Wielscher
AU - Carlos Márquez-Burgoa
AU - Anastasiya Hladik
AU - Simone Rizzetto
AU - Lisa E. Shaw
AU - Minoo Ghannadan
AU - Stephanie A. Gerhofer
AU - Andrew J. Mitchell
AU - Maria Elizabeth Torres-Pacheco
AU - Fabio Luciani
AU - Matthias Farlik
AU - Justin J. L. Wong
AU - Sylvia Knapp
AU - Philipp Starkl
AU - Stuart T. Fraser
AU - Steffen Jung
AU - Wolfgang Weninger
PY - 2026
DA - 2026/10/26
JO - Nature Immunology
DO - 10.1038/s41590-026-02686-1
UR - https://doi.org/10.1038/s41590-026-02686-1
AB - Tissue-resident macrophages originate from distinct developmental sources, but their adult replenishment is thought to depend exclusively on circulating monocytes. Here we identify a previously unrecognized CD4-lineage erythro–myeloid progenitor (EMPROR) in the adult bone marrow that provides an alternative pathway for macrophage generation. EMPROR cells are phenotypically and transcriptionally distinct from hematopoietic stem cells, common myeloid progenitors and monocyte precursors, lacking Csf1r and Ccr2 while expressing Cd4 and Kit. Single-cell RNA sequencing, RNA velocity analysis and lineage assays reveal macrophage, neutrophil, megakaryocytic and erythroid potential. EMPROR cells generate perivascular and tumor-associated macrophages independently of CCR2-mediated monocyte recruitment and contribute to erythroid and granulocytic lineages under inflammatory and neoplastic conditions. Transcriptomic comparisons position EMPROR cells closest to embryonic erythro–myeloid progenitors, indicating the persistence of an embryonic-like program in adult bone marrow. These findings reveal an alternative pathway of adult myelopoiesis that sustains macrophage diversity beyond the classical monocyte lineage.
SN - 1529-2908
SN - 1529-2916
ER -