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Endosteal stem cells in young bone marrow dictate active osteogenesis and aggressive tumorigenesis

ABSTRACT: Endosteal stem cells in young bone marrow dictate active osteogenesis and aggressive tumorigenesis

PROVIDER: PRJNA770752 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR16304014.fastq.gz	Fastqsanger.gz
	SRR16304021_1.fastq.gz	Fastqsanger.gz
	SRR16304021_2.fastq.gz	Fastqsanger.gz
	SRR16304022_1.fastq.gz	Fastqsanger.gz

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Bone marrow endosteal stem cells dictate active osteogenesis and aggressive tumorigenesis.

Project description:The bone marrow contains various populations of skeletal stem cells (SSCs) in the stromal compartment, which are important regulators of bone formation. It is well-described that leptin receptor (LepR)+ perivascular stromal cells provide a major source of bone-forming osteoblasts in adult and aged bone marrow. However, the identity of SSCs in young bone marrow and how they coordinate active bone formation remains unclear. Here we show that bone marrow endosteal SSCs are defined by fibroblast growth factor receptor 3 (Fgfr3) and osteoblast-chondrocyte transitional (OCT) identities with some characteristics of bone osteoblasts and chondrocytes. These Fgfr3-creER-marked endosteal stromal cells contribute to a stem cell fraction in young stages, which is later replaced by Lepr-cre-marked stromal cells in adult stages. Further, Fgfr3+ endosteal stromal cells give rise to aggressive osteosarcoma-like lesions upon loss of p53 tumor suppressor through unregulated self-renewal and aberrant osteogenic fates. Therefore, Fgfr3+ endosteal SSCs are abundant in young bone marrow and provide a robust source of osteoblasts, contributing to both normal and aberrant osteogenesis.

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Endosteal stem cells in young bone marrow dictate active osteogenesis and aggressive tumorigenesis

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Project description:A subset of osteoblasts functions as a key component of the hematopoietic stem cell niche. But it is still unclear that the precise cellular and molecular contribution of endosteal cell populations on the HSC supportive microenvironment. We purified the endosteal cells and subdivided them into mesenchymal progenitor cells (MPCs: ALCAM(-)Sca-1(+)) and two osteoblast populations (ALCAM(-)Sca-1(-) and ALCAM(+)Sca-1(-)). In this study, to clarify the characteristics of these fractionated cells in detail, gene expression analysis were performed using the GeneChip Mouse Genome Array 430 2.0 (Affymetrix). The bone fragments of femur and tibiae were treated with collagenase and endosteal cells were obtained. For enrichment of non-hematopoietic and non-endothelial population, CD45(-)CD31(-)Ter119(-) population was isolated and then the expressions of Sca-1 and activated leukocyte cell adhesion molecule (ALCAM) was analyzed by FACS. FACS analysis showed that CD45(-)CD31(-)Ter119(-) cells were subdivided into ALCAM(-)Sca-1(+), ALCAM(-)Sca-1(-) and ALCAM(+)Sca-1(-). These three populations were sorted and RNA samples were used for amplification, labeling, and hybridization to independent arrays.

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