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Recapitulation of endochondral ossification by hPSC-derived SOX9+ sclerotomal progenitors
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Recapitulation of endochondral ossification by hPSC-derived SOX9+ sclerotomal progenitors
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Journal Article
Recapitulation of endochondral ossification by hPSC-derived SOX9+ sclerotomal progenitors
2025
Overview
Endochondral ossification generates most of the load-bearing bones, recapitulating it in human cells remains a challenge. Here, we report generation of
SOX9
+
sclerotomal progenitors (scl-progenitors), a mesenchymal precursor at the pre-condensation stage, from human pluripotent stem cells and development of osteochondral induction methods for these cells. Upon lineage-specific induction,
SOX9
+
scl-progenitors have not only generated articular cartilage but have also undergone spontaneous condensation, cartilaginous anlagen formation, chondrocyte hypertrophy, vascular invasion, and finally bone formation with stroma, thereby recapitulating key stages during endochondral ossification. Moreover, self-organized growth plate-like structures have also been induced using
SOX9
+
scl-progenitor-derived fusion constructs with chondro- and osteo-spheroids, exhibiting molecular and cellular similarities to the primary growth plates. Furthermore, we have identified
ITGA9
as a specific surface marker for reporter-independent isolation of
SOX9
+
scl-progenitors and established a culture system to support their expansion. Our work highlights
SOX9
+
scl-progenitors as a promising tool for modeling human skeletal development and bone/cartilage bioengineering.
Endochondral ossification is hard to recapitulate with human cells. Here, the authors generated SOX9+ sclerotomal progenitors from hPSCs, modeling key developmental stages of bone development and growth plate-like structures.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/107
/ 13/31
/ 14/19
/ 14/32
/ 38/39
/ 38/91
/ Bones
/ Cartilage, Articular - cytology
/ Cartilage, Articular - metabolism
/ Humanities and Social Sciences
/ Humans
/ Mesenchymal Stem Cells - cytology
/ Mesenchymal Stem Cells - metabolism
/ Pluripotent Stem Cells - cytology
/ Pluripotent Stem Cells - metabolism
/ Science
/ SOX9 Transcription Factor - genetics
/ SOX9 Transcription Factor - metabolism
/ Stroma
