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| Status |
Public on Feb 02, 2022 |
| Title |
GDF5+ chondroprogenitors derived from human pluripotent stem cells, which resemble embryonic teno/ligamento-genic cells, preferentially form permanent chondrocytes |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: Human pluripotent stem cells (hPSCs) give rise to chondrogenic activity in culture. Such activity was found in mesodermal and neural crest like progeny of hPSCs, and readily expanded as SOX9+ msenchymal cells in a medium containing FGF2. However, once expanded, the type of chondrocytes they perfer to form is growth plate-ike transient chondrocytes that are destined to form bone. However, we have recently developed a method to generate GDF5+ mesenchymal cells from such SOX9+ cells which ehibit activity to preferentially form articular-like permanent chondrocytes. The aim of the present prospective follow-up study was to reveal the cell-type and developmental origin of the GDF5+ cells as well as the SOX9+ cells.
Methods: Paraxial mesoderm was generated from human PSCs, purified by FACS, and expanded to generate SOX9+ chondroprogenitors. Then, the SOX9+ cells were further differentiated into joint progenitor-like GDF5+ chondroprogenitors. These two chondroprogenitors were subjcted to bulk RNA-seq.
Results: Based on the transcriptomic data, we examined differentially expressed genes, cell-type deconvolution analysis, and cell-type correlation analysis. The results suggested that GDF5+ cells might contain a teno/ligamento-genic potential (e.g., SCX+ cells), while SOX9+ cells were related to (neural crest-derived) ectomesenchymal chondroprogenitors. The followup biological analyses indicated as follows. The fast-growing SOX9+ cells formed cartilage that expressed chondrocyte hypertrophy markers and was readily mineralized after ectopic transplantation. In contrast, the slowly-growing GDF5+ cells were derived from SOX9+ cells. They formed cartilage that tended to express low to no chondrocyte hypertrophy markers, while expressing PRG4, a marker of embryonic articular chondrocytes, and to remain largely unmineralized in vivo.
Conclusions: Our results imply that GDF5+ cells specified to generate permanent-like cartilage are likely to emerge in association with the commitment of SOX9+ cells to the tendon/ligament lineage.
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| Overall design |
Bulk RNA-seq data of 4 SOX9+ chondogenic cells and 4 GDF5+ chondrogenic cells generated independently from human pluripotent stem cells were generated by deep sequencing.
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| Citation missing |
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| Submission date |
Feb 10, 2020 |
| Last update date |
Feb 02, 2022 |
| Contact name |
Guangsheng Pei |
| E-mail(s) |
[email protected]
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| Phone |
7135697578
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| Organization name |
UTHealth
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| Street address |
7000 Fanin
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| City |
Houston |
| State/province |
Texas |
| ZIP/Postal code |
77030 |
| Country |
USA |
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| Platforms (1) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA605801 |
| SRA |
SRP247990 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE145048_FPKM_Expression_Matrix.txt.gz |
551.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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