TY - JOUR
T1 - A mesoderm-derived precursor for mesenchymal stem and endothelial cells
AU - Vodyanik, Maxim A.
AU - Yu, Junying
AU - Zhang, Xin
AU - Tian, Shulan
AU - Stewart, Ron
AU - Thomson, James A.
AU - Slukvin, Igor I.
N1 - Funding Information:
We thank Toru Nakano for providing OP9 cells, Dietmar Vestweber for providing endomucin antibodies, Gordon Keller for providing HES2.R26tdRFP hESC line, Mitchell Probasco for cell sorting, Clay Glennon for time-lapse photography, and Joan Larson and Krista Eastman for editorial assistance. This work was supported by funds from the National Institutes of Health (R01 HL081962, P01 GM081629, and P51 RR000167) and the Charlotte Geyer Foundation. J.A.T. owns stock, serves on the Board of Directors, and serves as Chief Scientific Officer of Cellular Dynamics International. J.A.T. also serves as Scientific Director of the WiCell Research Institute. I.I.S. owns stock and is the scientific founder of Cellular Dynamics International.
PY - 2010/12/3
Y1 - 2010/12/3
N2 - Among the three embryonic germ layers, the mesoderm is a major source of the mesenchymal precursors giving rise to skeletal and connective tissues, but these precursors have not previously been identified and characterized. Using human embryonic stem cells directed toward mesendodermal differentiation, we show that mesenchymal stem/stromal cells (MSCs) originate from a population of mesodermal cells identified by expression of apelin receptor. In semisolid medium, these precursors form FGF2-dependent compact spheroid colonies containing mesenchymal cells with a transcriptional profile representative of mesoderm-derived embryonic mesenchyme. When transferred to adherent cultures, individual colonies give rise to MSC lines with chondro-, osteo-, and adipogenic differentiation potentials. Although the MSC lines lacked endothelial potential, endothelial cells could be derived from the mesenchymal colonies, suggesting that, similar to hematopoietic cells, MSCs arise from precursors with angiogenic potential. Together, these studies identified a common precursor of mesenchymal and endothelial cells, mesenchymoangioblast, as the source of mesoderm-derived MSCs.
AB - Among the three embryonic germ layers, the mesoderm is a major source of the mesenchymal precursors giving rise to skeletal and connective tissues, but these precursors have not previously been identified and characterized. Using human embryonic stem cells directed toward mesendodermal differentiation, we show that mesenchymal stem/stromal cells (MSCs) originate from a population of mesodermal cells identified by expression of apelin receptor. In semisolid medium, these precursors form FGF2-dependent compact spheroid colonies containing mesenchymal cells with a transcriptional profile representative of mesoderm-derived embryonic mesenchyme. When transferred to adherent cultures, individual colonies give rise to MSC lines with chondro-, osteo-, and adipogenic differentiation potentials. Although the MSC lines lacked endothelial potential, endothelial cells could be derived from the mesenchymal colonies, suggesting that, similar to hematopoietic cells, MSCs arise from precursors with angiogenic potential. Together, these studies identified a common precursor of mesenchymal and endothelial cells, mesenchymoangioblast, as the source of mesoderm-derived MSCs.
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U2 - 10.1016/j.stem.2010.11.011
DO - 10.1016/j.stem.2010.11.011
M3 - Article
C2 - 21112566
AN - SCOPUS:78649647544
SN - 1934-5909
VL - 7
SP - 718
EP - 729
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 6
ER -