Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production

Yoon A. Kang, Hyojung Paik, Si Yi Zhang, Jonathan J. Chen, Oakley C. Olson, Carl A. Mitchell, Amelie Collins, James W. Swann, Matthew R. Warr, Rong Fan, Emmanuelle Passegíe

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Hematopoietic stem cells (HSC) and downstream lineage-biased multipotent progenitors (MPP) tailor blood production and control myelopoiesis on demand. Recent lineage tracing analyses revealed MPPs to be major functional contributors to steadystate hematopoiesis. However, we still lack a precise resolution of myeloid differentiation trajectories and cellular heterogeneity in the MPP compartment. Here, we found that myeloid-biased MPP3 are functionally and molecularly heterogeneous, with a distinct subset of myeloid-primed secretory cells with high endoplasmic reticulum (ER) volume and FcγR expression. We show that FcγR+/ERhigh MPP3 are a transitional population serving as a reservoir for rapid production of granulocyte/macrophage progenitors (GMP), which directly amplify myelopoiesis through inflammation-triggered secretion of cytokines in the local bone marrow (BM) microenvironment. Our results identify a novel regulatory function for a secretory MPP3 subset that controls myeloid differentiation through lineage-priming and cytokine production and acts as a selfreinforcing amplification compartment in inflammatory stress and disease conditions.

Original languageEnglish
Article numbere20230088
JournalJournal of Experimental Medicine
Volume220
Issue number8
DOIs
StatePublished - Aug 7 2023

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