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Comparative analysis of gene expression identifies distinct molecular signatures of bone marrow- and periosteal skeletal stem/progenitor cells

ABSTRACT: Genetic comparison between periosteal skeletal stem cells and bone marrow skeletal stem cells in mice

ORGANISM(S): Mus musculus

PROVIDER: GSE107798 | GEO | 2017/12/08

SECONDARY ACCESSION(S): PRJNA421427

REPOSITORIES: GEO

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Periosteal skeletal stem cells can migrate into the bone marrow and support hematopoiesis after injury [I]

Project description:To investigate the transcriptomic differences between bone marrow mesenchymals stem cells and periosteal skeletal stem cells at steady state, and periosteal skeletal stem cells 72 hours after bone transplantation

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Comparative analysis of gene expression identifies distinct molecular signatures of bone marrow- and periosteal-skeletal stem/progenitor cells.

Project description:Periosteum and bone marrow (BM) both contain skeletal stem/progenitor cells (SSCs) that participate in fracture repair. However, the functional difference and selective regulatory mechanisms of SSCs in different locations are unknown due to the lack of specific markers. Here, we report a comprehensive gene expression analysis of bone marrow SSCs (BM-SSCs), periosteal SSCs (P-SSCs), and more differentiated osteoprogenitors by using reporter mice expressing Interferon-inducible Mx1 and NestinGFP, previously known SSC markers. We first defined that the BM-SSCs can be enriched by the combination of Mx1 and NestinGFP expression, while endogenous P-SSCs can be isolated by positive selection of Mx1, CD105 and CD140a (known SSC markers) combined with the negative selection of CD45, CD31, and osteocalcinGFP (a mature osteoblast marker). Comparative gene expression analysis with FACS-sorted BM-SSCs, P-SSCs, Osterix+ preosteoblasts, CD51+ stroma cells and CD45+ hematopoietic cells as controls revealed that BM-SSCs and P-SSCs have high similarity with few potential differences without statistical significance. We also found that CD51+ cells are highly heterogeneous and have little overlap with SSCs. This was further supported by the microarray cluster analysis, where the two SSC populations clustered together but are separate from the CD51+ cells. However, when comparing SSC population to controls, we found several genes that are uniquely upregulated in endogenous SSCs. Amongst these genes, we found KDR (aka Flk1 or VEGFR2) to be most interesting and discovered that it is highly and selectively expressed in P-SSCs. This finding suggests that endogenous P-SSCs are functionally very similar to BM-SSCs with undetectable significant differences in gene expression but there are distinct molecular signatures in P-SSCs, which can be useful to specify P-SSC subset in vivo.

| S-EPMC5771600 | biostudies-literature

Comparative analysis of gene expression identifies distinct molecular signatures of bone marrow- and periosteal skeletal stem/progenitor cells

Project description:Comparative analysis of gene expression identifies distinct molecular signatures of bone marrow- and periosteal skeletal stem/progenitor cells

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Periosteal skeletal stem cells can migrate into the bone marrow and support hematopoiesis after injury [II]

Project description:To investigate the transcriptomic differences between bone marrow mesenchymals stem cells and periosteal skeletal stem cells at steady state, and graft bone marrow mesenchymal stem cells 5 months after transplantation

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RNAseq of periosteal stem/progenitor cells from patients with congenital pseudarthrosis of the tibia

Project description:Congenital pseudarthrosis of the tibia (CPT) is a severe pediatric disorder affecting children. CPT is characterized by tibial bowing at birth leading to spontaneous fracture and fibrous non-union. Our study showed the presence of biallelic inactivation of the NF1 gene in the periosteum and in periosteal skeletal/stem progenitor cells (pSSPCs) at the pseudarthrosis site.

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Skeletal stem/progenitor cells in periosteum and skeletal muscle share a common molecular response to bone injury

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Periosteal skeletal stem cells can migrate into the bone marrow and support hematopoiesis after injury

Project description:Periosteal skeletal stem cells can migrate into the bone marrow and support hematopoiesis after injury

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Sfrp4 is Required to Maintain Ctsk-Lineage Periosteal Stem Cell Niche Function

Project description:The periosteum contains cells which function as a reservoir of stem cells and progenitors and contribute to cortical expansion during growth, cortical bone homeostasis and repair. However, the local or paracrine factors that govern stem cell renewal and differentiation within the periosteal niche remains elusive. Cathepsin K (Ctsk) together with additional cell surface markers marks a subset of stem cells in the periosteum (PSC) which possess self-renewal ability and inducible multipotency. These PSCs produce osteoblasts mediating periosteal bone formation and fracture repair. Sfrp4 is expressed in periosteal Ctsk-lineage cells and using CtskCre mice that are either wild type or Sfrp4-/-, we report here that Sfrp4 deletion decreases the pool of PSCs, impairs their self-renewal, their ability to give rise to their derivatives and their clonal multipotency for differentiation into osteoblasts and chondrocytes in vitro and formation of bone organoids in vivo. Bulk RNA sequencing analysis in Ctsk-lineage PSCs demonstrated that Sfrp4 deletion leads to downregulation of signaling pathways associated with skeletal development, positive regulation of bone mineralization and wound healing. Sfrp4 deletion hampers the Ctsk-lineage PSC response and recruitment after bone injury and leads to an impaired periosteal response. Periosteal Ctsk-lineage cells respond to PTH(1-34) treatment with an increase in the % of PSCs, a response not seen in the absence of Sfrp4. Importantly, bone histomorphometry analysis showed that in the absence of Sfrp4, PTH(1-34)-dependent increase in cortical thickness, periosteal bone formation is markedly impaired.

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