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Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production

ABSTRACT: Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production

PROVIDER: PRJNA753832 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15416514_1.fastq.gz	Fastqsanger.gz
	SRR15416514_2.fastq.gz	Fastqsanger.gz
	SRR15416515_1.fastq.gz	Fastqsanger.gz
	SRR15416515_2.fastq.gz	Fastqsanger.gz
	SRR15416516_1.fastq.gz	Fastqsanger.gz

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Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production

Project description:Hematopoietic stem cells (HSC) and downstream lineage-biased multipotent progenitors (MPP) tailor blood production and control myelopoiesis on demand. However, a precise resolution of myeloid differentiation trajectories and cellular heterogeneity in various MPP populations and understanding of their role in controlling myeloid cell production remains largely lacking. Here, we analyze that myeloid-biased MPP3 are functionally and molecularly heterogenous, with a distinct subset of myeloid-primed secretory cells with high endoplasmic reticulum (ER) volume.

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Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production.

Project 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+/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 self-reinforcing amplification compartment in inflammatory stress and disease conditions.

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