Transient expansion and myofibroblast conversion of marrow adipogenic lineage precursors (MALPs) mediate bone marrow repair after radiation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA699312 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13623161_1.fastq.gz | Fastqsanger.gz | |||
| SRR13623161_2.fastq.gz | Fastqsanger.gz |
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Project description:Radiation causes a collapse of bone marrow cells and elimination of microvasculature. Bone marrow has a limited regenerative ability and the mechanism governing such recovery is largely unknown. Mesenchymal lineage cells provide supportive microenvironment for hematopoiesis and angiogenesis in bone. We recently discovered a non-proliferative mesenchymal subpopulation, marrow adipogenic lineage precursors (MALPs), that express most adipogenic markers with no lipid accumulation. To investigate the acute radiation effects, we performed single cell RNA-sequencing (scRNA-seq) on bone marrow mesenchymal lineage cells at day 3 after focal radiation. Interestingly, computational analysis revealed that MALPs become highly proliferative and acquire myofibroblast features after radiation. Using an adipocyte-specific Adipoq-Cre to label MALPs in vivo, we found that radiation indeed rapidly and transiently expands MALPs. MALPs have a cell body with multiple cell processes that form a 3D network inside bone marrow. Shortly after radiation, MALPs lost most of cell processes, became more elongated, and highly expressed myofibroblast-related genes, coinciding with marrow vessel dilation and diminished bone marrow cellularity. Later when vessels and hematopoietic cells recovered, MALPs returned to the baseline number and a normal reticular shape. Ablation of MALPs completely blocked the recovery of bone marrow vasculature and cellularity, including hematopoietic stem and progenitors. MALPs highly express several hematopoietic and angiogenic factors. Depleting one of them, VEGFa, specifically in MALPs, delayed bone marrow recovery after radiation. Taken together, our research demonstrates a critical role of MALPs in mediating the marrow repair after radiation injury and sheds light on a new cellular target for treating marrow suppression after radiotherapy.
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