TY - JOUR
T1 - Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes
AU - Ferguson, Gabriel B.
AU - Van Handel, Ben
AU - Bay, Maxwell
AU - Fiziev, Petko
AU - Org, Tonis
AU - Lee, Siyoung
AU - Shkhyan, Ruzanna
AU - Banks, Nicholas W.
AU - Scheinberg, Mila
AU - Wu, Ling
AU - Saitta, Biagio
AU - Elphingstone, Joseph
AU - Larson, A. Noelle
AU - Riester, Scott M.
AU - Pyle, April D.
AU - Bernthal, Nicholas M.
AU - Mikkola, Hanna Ka
AU - Ernst, Jason
AU - van Wijnen, Andre J.
AU - Bonaguidi, Michael
AU - Evseenko, Denis
N1 - Funding Information:
We would like to acknowledge Drs. Gage Crump and Andy McMahon for critical reading of the manuscript. De-identified human cartilage samples were collected under UCLA IRB# 10-001857. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Awards K01AR061415 and R01AR071734 to D.E. A.D.P. was supported by NIH NIAMS R01AR064327 andCIRM DISC2-10695. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. T.O. was supported by the Estonian Research Council (personal research grant PUT1177). N.M.B. was supported by 5K08AR069112-01. This work was also supported by DOD grant W81XWH-13-1-0465 and CIRM grants RB5-07230 and TRAN1-09288, all to D.E.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-018-05573-y
DO - 10.1038/s41467-018-05573-y
M3 - Article
C2 - 30194383
AN - SCOPUS:85053020414
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3634
ER -