Dataset Information

Label-free quantitative proteomics analysis of bone marrow cells of MK-LCM WT versus KO mice

ABSTRACT: High ploidy large cytoplasmic megakaryocytes (LCM) are critical negative regulators of hematopoietic stem cells (HSC) and are responsible for platelet formation. Using a mouse knockout model with normal megakaryocyte numbers but essentially devoid of LCM (MK-LCM KO), we demonstrated a pronounced increase in bone marrow HSC concurrent with endogenous mobilization and extramedullary hematopoiesis. When HSC isolated from a MK-LCM KO microenvironment were transplanted in lethally irradiated mice, the absence of LCM increased HSC in BM, blood and spleen. Severe thrombocytopenia was observed in animals with diminished LCM, although there was no change in megakaryocyte ploidy distribution. In contrast, WT HSC-generated LCM regulated a normal HSC pool and prevented thrombocytopenia. The present label-free quantitative LC-MSMS data was used to determine proteins that are differentially expressed in bone marrow cells of MK-LCM WT versus MK-LCM KO mice.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Cell, Bone Marrow

DISEASE(S): Thrombocytopenia

SUBMITTER: Thomas Nebl

LAB HEAD: Tom Nebl

PROVIDER: PXD040423 | Pride | 2023-05-10

REPOSITORIES: Pride

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Publications

High ploidy large cytoplasmic megakaryocytes are hematopoietic stem cells regulators and essential for platelet production.

Heazlewood Shen Y SY Ahmad Tanveer T Cao Benjamin B Cao Huimin H Domingues Melanie M Sun Xuan X Heazlewood Chad K CK Li Songhui S Williams Brenda B Fulton Madeline M White Jacinta F JF Nebl Tom T Nefzger Christian M CM Polo Jose M JM Kile Benjamin T BT Kraus Felix F Ryan Michael T MT Sun Yu B YB Choong Peter F M PFM Ellis Sarah L SL Anko Minna-Liisa ML Nilsson Susan K SK

Nature communications 20230413 1

Megakaryocytes (MK) generate platelets. Recently, we and others, have reported MK also regulate hematopoietic stem cells (HSC). Here we show high ploidy large cytoplasmic megakaryocytes (LCM) are critical negative regulators of HSC and critical for platelet formation. Using a mouse knockout model (Pf4-Srsf3<sup>Δ/Δ</sup>) with normal MK numbers, but essentially devoid of LCM, we demonstrate a pronounced increase in BM HSC concurrent with endogenous mobilization and extramedullary hematopoiesis. ...[more]

PMID: 37055407

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Project description:The hematopoietic system gives rise to a heterogeneous population of terminally differentiated cells that reside in the bone marrow (BM) to fulfill their roles in immunity, blood clotting and tissue oxygenation. Hematopoietic stem and progenitor cells are at the apex of a hierarchically organized maturation cascade constantly replenishing the pool of differentiated cells to maintain blood cell homeostasis. The bone marrow microenvironment is functionally compartmentalized by heterogeneous niche cells that provide physical and soluble signals to spatio-temporally organize hematopoiesis. Megakaryocytes (MKs) are niche cells of hematopoietic origin that support hematopoietic stem cell (HSCs) homeostasis and generate circulating platelets. Platelet production involves the release of MK fragments while their cell body is entirely consumed in a process termed thrombopoiesis. Consequently, replenishment of fragmented MKs from MK progenitors (termed megakaryopoiesis) is required to ensure sufficient platelet production, but also to maintain MK homeostasis within the HSC niche. Here, we used intravital imaging of the megakaryocytic lineage to identify the spatio-temporal patterns of megakaryopoiesis during steady state and thrombocytopenia. We show that MK consumption during thrombopoiesis is compensated by immediate and local proliferation of MK progenitors. MK homeostasis is controlled by plasmacytoid dendritic cells (pDCs) that scan the BM and secrete Interferon alpha (INFa) upon detection of exhausted megakaryocytes to trigger megakaryopoiesis. We identified local pDC-derived INFa release as a physiological inflammatory stimulus of the bone marrow niche that synchronizes megakaryopoiesis and thrombopoiesis to maintain homeostasis of MKs and platelets in steady state and under stress. Viral infection with SARS-CoV-2 can manipulate pDC-driven MK proliferation leading to inappropriate megakaryopoiesis, which has been associated with thrombotic complications during COVID-19.

Dataset Information

Label-free quantitative proteomics analysis of bone marrow cells of MK-LCM WT versus KO mice

Publications

High ploidy large cytoplasmic megakaryocytes are hematopoietic stem cells regulators and essential for platelet production.

Similar Datasets

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