Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes

Gabriel B. Ferguson, Ben Van Handel, Maxwell Bay, Petko Fiziev, Tonis Org, Siyoung Lee, Ruzanna Shkhyan, Nicholas W. Banks, Mila Scheinberg, Ling Wu, Biagio Saitta, Joseph Elphingstone, A. Noelle Larson, Scott M. Riester, April D. Pyle, Nicholas M. Bernthal, Hanna KA Mikkola, Jason Ernst, Andre J. Wijnen, Michael Bonaguidi and Denis Evseenko ()
Additional contact information
Gabriel B. Ferguson: University of Southern California (USC)
Ben Van Handel: University of Southern California (USC)
Maxwell Bay: USC
Petko Fiziev: UCLA
Tonis Org: UCLA
Siyoung Lee: University of Southern California (USC)
Ruzanna Shkhyan: University of Southern California (USC)
Nicholas W. Banks: University of Southern California (USC)
Mila Scheinberg: University of Southern California (USC)
Ling Wu: InVitro Cell Research, LLC
Biagio Saitta: University of Southern California (USC)
Joseph Elphingstone: University of Southern California (USC)
A. Noelle Larson: Center of Regenerative Medicine, Mayo Clinic
Scott M. Riester: Center of Regenerative Medicine, Mayo Clinic
April D. Pyle: Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA
Nicholas M. Bernthal: David Geffen School of Medicine, UCLA
Hanna KA Mikkola: Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA
Jason Ernst: UCLA
Andre J. Wijnen: Center of Regenerative Medicine, Mayo Clinic
Michael Bonaguidi: USC
Denis Evseenko: University of Southern California (USC)

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: Abstract Tissue-specific gene expression defines cellular identity and function, but knowledge of early human development is limited, hampering application of cell-based therapies. Here we profiled 5 distinct cell types at a single fetal stage, as well as chondrocytes at 4 stages in vivo and 2 stages during in vitro differentiation. Network analysis delineated five tissue-specific gene modules; these modules and chromatin state analysis defined broad similarities in gene expression during cartilage specification and maturation in vitro and in vivo, including early expression and progressive silencing of muscle- and bone-specific genes. Finally, ontogenetic analysis of freshly isolated and pluripotent stem cell-derived articular chondrocytes identified that integrin alpha 4 defines 2 subsets of functionally and molecularly distinct chondrocytes characterized by their gene expression, osteochondral potential in vitro and proliferative signature in vivo. These analyses provide new insight into human musculoskeletal development and provide an essential comparative resource for disease modeling and regenerative medicine.

Date: 2018
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DOI: 10.1038/s41467-018-05573-y

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