Use of RUNX2 expression to identify osteogenic progenitor cells derived from human embryonic stem cells

Li Zou; Fahad K. Kidwai; Ross A. Kopher; Jason Motl; Cory A. Kellum; Jennifer J. Westendorf; Dan S. Kaufman

doi:10.1016/j.stemcr.2015.01.008

Use of RUNX2 expression to identify osteogenic progenitor cells derived from human embryonic stem cells

Li Zou, Fahad K. Kidwai, Ross A. Kopher, Jason Motl, Cory A. Kellum, Jennifer J. Westendorf, Dan S. Kaufman

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

We generated a RUNX2-yellow fluorescent protein (YFP) reporter system to study osteogenic development from human embryonic stem cells (hESCs). Our studies demonstrate the fidelity of YFP expression with expression of RUNX2 and other osteogenic genes in hESC-derived osteoprogenitor cells, as well as the osteogenic specificity of YFP signal. In vitro studies confirm that the hESC-derived YFP⁺ cells have similar osteogenic phenotypes to osteoprogenitor cells generated from bone-marrow mesenchymal stem cells. In vivo studies demonstrate the hESC-derived YFP⁺ cells can repair a calvarial defect in immunodeficient mice. Using the engineered hESCs, we monitored the osteogenic development and explored the roles of osteogenic supplements BMP2 and FGF9 in osteogenic differentiation of these hESCs in vitro. Taken together, this reporter system provides a novel system to monitor the osteogenic differentiation of hESCs and becomes useful to identify soluble agents and cell signaling pathways that mediate early stages of human bone development.

Original language	English (US)
Pages (from-to)	190-198
Number of pages	9
Journal	Stem Cell Reports
Volume	4
Issue number	2
DOIs	https://doi.org/10.1016/j.stemcr.2015.01.008
State	Published - Feb 10 2015

Bibliographical note

Funding Information:
We graciously thank Dr. Andre J. van Wijnen (Mayo Clinic) for part of the RUNX2 vector, Bonita VanHeel for microCT imaging, Li Li for cell-culture assistance, and Patrick Ferrell and David L. Hermanson for manuscript editing. This work is supported by NIH/NIDCR grants DE022556 (D.S.K.) and R90 DE023058 (F.K.K.).

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title = "Use of RUNX2 expression to identify osteogenic progenitor cells derived from human embryonic stem cells",

abstract = "We generated a RUNX2-yellow fluorescent protein (YFP) reporter system to study osteogenic development from human embryonic stem cells (hESCs). Our studies demonstrate the fidelity of YFP expression with expression of RUNX2 and other osteogenic genes in hESC-derived osteoprogenitor cells, as well as the osteogenic specificity of YFP signal. In vitro studies confirm that the hESC-derived YFP+ cells have similar osteogenic phenotypes to osteoprogenitor cells generated from bone-marrow mesenchymal stem cells. In vivo studies demonstrate the hESC-derived YFP+ cells can repair a calvarial defect in immunodeficient mice. Using the engineered hESCs, we monitored the osteogenic development and explored the roles of osteogenic supplements BMP2 and FGF9 in osteogenic differentiation of these hESCs in vitro. Taken together, this reporter system provides a novel system to monitor the osteogenic differentiation of hESCs and becomes useful to identify soluble agents and cell signaling pathways that mediate early stages of human bone development.",

author = "Li Zou and Kidwai, {Fahad K.} and Kopher, {Ross A.} and Jason Motl and Kellum, {Cory A.} and Westendorf, {Jennifer J.} and Kaufman, {Dan S.}",

note = "Funding Information: We graciously thank Dr. Andre J. van Wijnen (Mayo Clinic) for part of the RUNX2 vector, Bonita VanHeel for microCT imaging, Li Li for cell-culture assistance, and Patrick Ferrell and David L. Hermanson for manuscript editing. This work is supported by NIH/NIDCR grants DE022556 (D.S.K.) and R90 DE023058 (F.K.K.). ",

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doi = "10.1016/j.stemcr.2015.01.008",

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AU - Zou, Li

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AU - Motl, Jason

AU - Kellum, Cory A.

AU - Westendorf, Jennifer J.

AU - Kaufman, Dan S.

N1 - Funding Information: We graciously thank Dr. Andre J. van Wijnen (Mayo Clinic) for part of the RUNX2 vector, Bonita VanHeel for microCT imaging, Li Li for cell-culture assistance, and Patrick Ferrell and David L. Hermanson for manuscript editing. This work is supported by NIH/NIDCR grants DE022556 (D.S.K.) and R90 DE023058 (F.K.K.).

PY - 2015/2/10

Y1 - 2015/2/10

N2 - We generated a RUNX2-yellow fluorescent protein (YFP) reporter system to study osteogenic development from human embryonic stem cells (hESCs). Our studies demonstrate the fidelity of YFP expression with expression of RUNX2 and other osteogenic genes in hESC-derived osteoprogenitor cells, as well as the osteogenic specificity of YFP signal. In vitro studies confirm that the hESC-derived YFP+ cells have similar osteogenic phenotypes to osteoprogenitor cells generated from bone-marrow mesenchymal stem cells. In vivo studies demonstrate the hESC-derived YFP+ cells can repair a calvarial defect in immunodeficient mice. Using the engineered hESCs, we monitored the osteogenic development and explored the roles of osteogenic supplements BMP2 and FGF9 in osteogenic differentiation of these hESCs in vitro. Taken together, this reporter system provides a novel system to monitor the osteogenic differentiation of hESCs and becomes useful to identify soluble agents and cell signaling pathways that mediate early stages of human bone development.

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Use of RUNX2 expression to identify osteogenic progenitor cells derived from human embryonic stem cells

Abstract

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