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Updated: Jul 28, 2025
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Blastomere Explants to Test for Cell Fate Commitment During Embryonic Development
Published on: January 26, 2013
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Systematic dissection of coordinated stromal remodeling identifies Sox10
Shawn M Sarkaria1, Junsong Zhou2, Suying Bao3
1Columbia Stem Cell Initiative, Department of Rehabilitation and Regenerative Medicine, Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA; Division of Hematology and Medical Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
Cell Stem Cell
|June 2, 2023
Summary
Primary myelofibrosis (PMF) involves bone marrow fibrosis. Glial cells, originating from leptin-receptor-positive mesenchymal cells, expand and drive fibrosis, offering a potential therapeutic target.
Area of Science:
- Hematology
- Cell Biology
- Oncology
Background:
- Bone marrow fibrosis is a hallmark of primary myelofibrosis (PMF).
- Stromal alterations in the bone marrow niche are poorly understood in disease pathogenesis.
- Leptin-receptor-positive (LepR+) mesenchymal cells are implicated in fibrotic processes.
Purpose of the Study:
- To investigate the cellular origins of myofibroblasts in PMF.
- To characterize stromal cell remodeling during PMF.
- To identify novel therapeutic targets for PMF.
Main Methods:
- Lineage tracing studies to identify cell origins.
- Single-cell RNA sequencing (scRNA-seq) for unbiased cellular profiling.
- Genetic and chemical ablation of specific cell populations.
Main Results:
- Myofibroblasts in PMF predominantly originate from LepR+ mesenchymal cells.
- scRNA-seq revealed altered expression of niche and fibrogenic factors in myofibroblasts.
- Bone marrow glial cells and pericytes expanded significantly, showing increased cell-cell signaling.
- Ablation of bone marrow glial cells reduced fibrosis and improved PMF pathology.
Conclusions:
- PMF involves complex remodeling of the bone marrow microenvironment.
- Glial cells play a critical role in PMF pathogenesis.
- Bone marrow glial cells represent a promising therapeutic target for PMF.
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