Dataset Information

Identification of the Human Skeletal Stem Cell.

ABSTRACT: Stem cell regulation and hierarchical organization of human skeletal progenitors remain largely unexplored. Here, we report the isolation of a self-renewing and multipotent human skeletal stem cell (hSSC) that generates progenitors of bone, cartilage, and stroma, but not fat. Self-renewing and multipotent hSSCs are present in fetal and adult bones and can also be derived from BMP2-treated human adipose stroma (B-HAS) and induced pluripotent stem cells (iPSCs). Gene expression analysis of individual hSSCs reveals overall similarity between hSSCs obtained from different sources and partially explains skewed differentiation toward cartilage in fetal and iPSC-derived hSSCs. hSSCs undergo local expansion in response to acute skeletal injury. In addition, hSSC-derived stroma can maintain human hematopoietic stem cells (hHSCs) in serum-free culture conditions. Finally, we combine gene expression and epigenetic data of mouse skeletal stem cells (mSSCs) and hSSCs to identify evolutionarily conserved and divergent pathways driving SSC-mediated skeletogenesis. VIDEO ABSTRACT.

SUBMITTER: Chan CKF

PROVIDER: S-EPMC6400492 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of the Human Skeletal Stem Cell.

Chan Charles K F CKF Gulati Gunsagar S GS Sinha Rahul R Tompkins Justin Vincent JV Lopez Michael M Carter Ava C AC Ransom Ryan C RC Reinisch Andreas A Wearda Taylor T Murphy Matthew M Brewer Rachel E RE Koepke Lauren S LS Marecic Owen O Manjunath Anoop A Seo Eun Young EY Leavitt Tripp T Lu Wan-Jin WJ Nguyen Allison A Conley Stephanie D SD Salhotra Ankit A Ambrosi Thomas H TH Borrelli Mimi R MR Siebel Taylor T Chan Karen K Schallmoser Katharina K Seita Jun J Sahoo Debashis D Goodnough Henry H Bishop Julius J Gardner Michael M Majeti Ravindra R Wan Derrick C DC Goodman Stuart S Weissman Irving L IL Chang Howard Y HY Longaker Michael T MT

Cell 20180901 1

Stem cell regulation and hierarchical organization of human skeletal progenitors remain largely unexplored. Here, we report the isolation of a self-renewing and multipotent human skeletal stem cell (hSSC) that generates progenitors of bone, cartilage, and stroma, but not fat. Self-renewing and multipotent hSSCs are present in fetal and adult bones and can also be derived from BMP2-treated human adipose stroma (B-HAS) and induced pluripotent stem cells (iPSCs). Gene expression analysis of individ ...[more]

PMID: 30241615

Similar Datasets

Project description:BACKGROUND:Better understanding of the signaling pathways that regulate human bone marrow stromal stem cell (hBMSC) differentiation into bone-forming osteoblasts is crucial for their clinical use in regenerative medicine. Chemical biology approaches using small molecules targeting specific signaling pathways are increasingly employed to manipulate stem cell differentiation fate. METHODS:We employed alkaline phosphatase activity and staining assays to assess osteoblast differentiation and Alizarin R staining to assess mineralized matrix formation of cultured hBMSCs. Changes in gene expression were assessed using an Agilent microarray platform, and data normalization and bioinformatics were performed using GeneSpring software. For in vivo ectopic bone formation experiments, hMSCs were mixed with hydroxyapatite-tricalcium phosphate granules and implanted subcutaneously into the dorsal surface of 8-week-old female nude mice. Hematoxylin and eosin staining and Sirius Red staining were used to detect bone formation in vivo. RESULTS:We identified several compounds which inhibited osteoblastic differentiation of hMSCs. In particular, we identified ruxolitinib (INCB018424) (3 ?M), an inhibitor of JAK-STAT signaling that inhibited osteoblastic differentiation and matrix mineralization of hMSCs in vitro and reduced ectopic bone formation in vivo. Global gene expression profiling of ruxolitinib-treated cells identified 847 upregulated and 822 downregulated mRNA transcripts, compared to vehicle-treated control cells. Bioinformatic analysis revealed differential regulation of multiple genetic pathways, including TGF? and insulin signaling, endochondral ossification, and focal adhesion. CONCLUSIONS:We identified ruxolitinib as an important regulator of osteoblast differentiation of hMSCs. It is plausible that inhibition of osteoblast differentiation by ruxolitinib may represent a novel therapeutic strategy for the treatment of pathological conditions caused by accelerated osteoblast differentiation and mineralization.

Dataset Information

Identification of the Human Skeletal Stem Cell.

Publications

Identification of the Human Skeletal Stem Cell.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets