Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production

Kang, Y.-A.; Paik, H.; Zhang, S. Y.; Chen, J.; Warr, M. R.; Fan, R.; Passegue, E.

doi:10.1101/2021.09.01.458573

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bioRxiv · 10.1101/2021.09.01.458573

Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production

Kang, Y.-A.·Paik, H.·Zhang, S. Y.·Chen, J.·Warr, M. R.·Fan, R.·Passegue, E.

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Abstract

Recent lineage tracing analyses revealed multipotent progenitors (MPP) to be major functional contributors to steady-state hematopoiesis (1-6). However, we are still lacking a precise resolution of myeloid differentiation trajectories and cellular heterogeneity in MPPs. Here, we found that myeloid-biased MPP3 (2, 3) are functionally and molecularly heterogeneous, with a distinct subset of myeloid-primed secretory cells with high endoplasmic reticulum (ER) volume and Fc{gamma}R expression. We show that Fc{gamma}R+/ERhigh MPP3 are a transitional population 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 subset of secretory MPP3 that controls myeloid differentiation through lineage-priming and cytokine production, and act as a self-reinforcing amplification compartment in stress and disease conditions. One-Sentence SummaryA secretory subset of multipotent hematopoietic progenitors augment myelopoiesis in stress and diseases conditions.

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Kang, Y.-A., Paik, H., Zhang, S. Y., Chen, J., Warr, M. R., Fan, R., Passegue, E.. 2021-09-02. Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production. https://doi.org/10.1101/2021.09.01.458573

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