GDF5+ chondroprogenitors derived from human pluripotent stem cells preferentially form permanent chondrocytes | Zendy

Azim Pothiawala | Zendy; Berke E. Sahbazoglu | Zendy; Bryan Ang | Zendy; Nadine Matthias | Zendy; Guangsheng Pei | Zendy; Qing Yan | Zendy; Brian R. Davis | Zendy; Johnny Huard | Zendy; Zhongming Zhao | Zendy; Naoki Nakayama | Zendy

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GDF5+ chondroprogenitors derived from human pluripotent stem cells preferentially form permanent chondrocytes

Author(s) -

Azim Pothiawala,

Berke E. Sahbazoglu,

Bryan Ang,

Nadine Matthias,

Guangsheng Pei,

Qing Yan,

Brian R. Davis,

Johnny Huard,

Zhongming Zhao,

Naoki Nakayama

Publication year - 2022

Publication title -

development

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.15

H-Index - 36

eISSN - 1477-9129

pISSN - 0950-1991

DOI - 10.1242/dev.196220

Subject(s) - biology , microbiology and biotechnology , induced pluripotent stem cell , chondrogenesis , stem cell , mesenchymal stem cell , cartilage , progenitor cell , embryonic stem cell , chondrocyte , stem cell transplantation for articular cartilage repair , sox9 , neural crest , cellular differentiation , anatomy , adult stem cell , embryo , genetics , transcription factor , gene

Mesodermal progeny of human pluripotent stem cells gave rise to two types of chondrogenic mesenchymal cells in culture: SOX9+ and GDF5+ cells. The fast-growing SOX9+ cells formed in vitro cartilage that expressed chondrocyte hypertrophy markers and readily underwent mineralization after ectopic transplantation. In contrast, the slowly growing GDF5+ cells derived from SOX9+ cells formed cartilage that tended to express low to no chondrocyte hypertrophy markers, while expressing PRG4, a marker of embryonic articular chondrocytes. The GDF5+-derived cartilage remained largely unmineralized in vivo. Interestingly, chondrocytes derived from the GDF5+ cells seemed to elicit these activities via cell non-autonomous mechanisms. Genome-wide transcriptomic analyses suggested that GDF5+ cells might contain a teno/ligamento-genic potential, while SOX9+ cells resembled neural crest-like progeny-derived chondroprogenitors. Thus, hPSC-derived GDF5+ cells specified to generate permanent-like cartilage seem to emerge coincidentally with the commitment of the SOX9+ progeny to the tendon/ligament lineage.

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