Instructive interaction between myelodysplastic hematopoiesis and the bone marrow microenvironment at the single-cell...

Area of Science:

• Hematology
• Oncology
• Cell Biology

Background:

• Myelodysplastic neoplasms (MDS) are a group of clonal hematopoietic stem cell disorders.
• MDS are hypothesized to alter the bone marrow (BM) microenvironment to support disease progression.

Purpose of the Study:

• To investigate the interactions between MDS cells and the BM niche at a single-cell level.
• To identify specific changes in nonhematopoietic cells within the BM microenvironment in response to MDS.

Main Methods:

• Analysis of over 13,000 murine niche cells in a patient-derived xenograft (PDX) model after MDS transplantation.
• Single-cell analysis of over 24,000 primary human bone marrow cells from MDS patients and healthy donors.
• Investigated mesenchymal stem cell (MSC) subpopulations and endothelial cells.

Main Results:

• MDS cells induced overexpression of hematopoietic factors (Cxcl12, Il7) in murine MSC subpopulations in the PDX model.
• Primary human MSC subpopulations from MDS patients exhibited significant heterogeneity.
• MDS-associated MSCs and endothelial cells showed inflammatory gene expression profiles and overexpression of Cxcl12, KIT ligand, and Il7.

Conclusions:

• MDS cells actively reprogram the bone marrow microenvironment.
• Altered MSC subpopulations with increased growth factor expression are characteristic of a subgroup of MDS patients.
• These findings highlight the critical role of the BM niche in MDS pathogenesis.