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Updated: Sep 3, 2025
Megakaryocyte Differentiation and Platelet Formation from Human Cord Blood-derived CD34+ Cells
Published on: December 27, 2017
Microbiota-Derived Propionate Modulates Megakaryopoiesis and Platelet Function
Kerstin Dürholz1,2, Eva Schmid1,2, Michael Frech1,2
1Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.
Abstract:
Rheumatoid arthritis (RA) is associated with an increased risk for cardiovascular events driven by abnormal platelet clotting effects. Platelets are produced by megakaryocytes, deriving from megakaryocyte erythrocyte progenitors (MEP) in the bone marrow. Increased megakaryocyte expansion across common autoimmune diseases was shown for RA, systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). In this context, we evaluated the role of the microbial-derived short chain fatty acid (SCFA) propionate on hematopoietic progenitors in the collagen induced inflammatory arthritis model (CIA) as we recently showed attenuating effects of preventive propionate treatment on CIA severity. In vivo, propionate treatment starting 21 days post immunization (dpi) reduced the frequency of MEPs in the bone marrow of CIA and naïve mice. Megakaryocytes numbers were reduced but increased the expression of the maturation marker CD61. Consistent with this, functional analysis of platelets showed an upregulated reactivity state following propionate-treatment. This was confirmed by elevated histone 3 acetylation and propionylation as well as by RNAseq analysis in Meg-01 cells. Taken together, we identified a novel nutritional axis that skews platelet formation and function.
Insights
Short chain fatty acids like propionate can influence platelet production in rheumatoid arthritis (RA). This study reveals how propionate impacts megakaryocyte progenitors, potentially altering platelet function and cardiovascular risk in autoimmune diseases.
Area of Science:
- Immunology
- Hematology
- Microbiome-Host Interactions
Background:
- Rheumatoid arthritis (RA) elevates cardiovascular event risk due to abnormal platelet activity.
- Platelets originate from megakaryocytes, which develop from megakaryocyte erythrocyte progenitors (MEPs) in bone marrow.
- RA, lupus, and Sjögren's syndrome exhibit increased megakaryocyte expansion.
Purpose of the Study:
- To investigate the effect of propionate, a microbial short-chain fatty acid, on hematopoietic progenitors.
- To understand propionate's role in the collagen-induced inflammatory arthritis (CIA) model, given its previously observed protective effects.
Main Methods:
- Utilized the collagen-induced inflammatory arthritis (CIA) mouse model.
- Administered propionate treatment starting 21 days post-immunization (dpi).
- Analyzed bone marrow hematopoietic progenitor populations (MEPs), megakaryocytes, and platelet markers (CD61) using flow cytometry and RNA sequencing.
Main Results:
- Propionate treatment reduced MEP frequency in CIA and naive mice.
- Megakaryocyte numbers decreased, but CD61 expression (maturation marker) increased.
- Functional platelet analysis revealed heightened reactivity, supported by epigenetic modifications (histone acetylation/propionylation) and RNAseq data in Meg-01 cells.
Conclusions:
- Identified a novel nutritional pathway involving microbial short-chain fatty acids impacting platelet production and function.
- Propionate influences megakaryocyte development and platelet reactivity, offering potential therapeutic insights for RA-associated cardiovascular risks.
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