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Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production
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 steady-state hematopoiesis. However, we still lack a precise res...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10140385/ https://www.ncbi.nlm.nih.gov/pubmed/37115584 http://dx.doi.org/10.1084/jem.20230088 |
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author | Kang, Yoon-A Paik, Hyojung Zhang, Si Yi Chen, Jonathan J. Olson, Oakley C. Mitchell, Carl A. Collins, Amelie Swann, James W. Warr, Matthew R. Fan, Rong Passegué, Emmanuelle |
author_facet | Kang, Yoon-A Paik, Hyojung Zhang, Si Yi Chen, Jonathan J. Olson, Oakley C. Mitchell, Carl A. Collins, Amelie Swann, James W. Warr, Matthew R. Fan, Rong Passegué, Emmanuelle |
author_sort | Kang, Yoon-A |
collection | PubMed |
description | 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 steady-state 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(+)/ER(high) 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 self-reinforcing amplification compartment in inflammatory stress and disease conditions. |
format | Online Article Text |
id | pubmed-10140385 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-101403852023-04-29 Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production Kang, Yoon-A Paik, Hyojung Zhang, Si Yi Chen, Jonathan J. Olson, Oakley C. Mitchell, Carl A. Collins, Amelie Swann, James W. Warr, Matthew R. Fan, Rong Passegué, Emmanuelle J Exp Med Article 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 steady-state 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(+)/ER(high) 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 self-reinforcing amplification compartment in inflammatory stress and disease conditions. Rockefeller University Press 2023-04-26 /pmc/articles/PMC10140385/ /pubmed/37115584 http://dx.doi.org/10.1084/jem.20230088 Text en © 2023 Kang et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kang, Yoon-A Paik, Hyojung Zhang, Si Yi Chen, Jonathan J. Olson, Oakley C. Mitchell, Carl A. Collins, Amelie Swann, James W. Warr, Matthew R. Fan, Rong Passegué, Emmanuelle Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production |
title | Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production |
title_full | Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production |
title_fullStr | Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production |
title_full_unstemmed | Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production |
title_short | Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production |
title_sort | secretory mpp3 reinforce myeloid differentiation trajectory and amplify myeloid cell production |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10140385/ https://www.ncbi.nlm.nih.gov/pubmed/37115584 http://dx.doi.org/10.1084/jem.20230088 |
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