2. Academic Validation
  3. Single cell transcriptomic analysis of human pluripotent stem cell chondrogenesis

Single cell transcriptomic analysis of human pluripotent stem cell chondrogenesis

  • Nat Commun. 2021 Jan 13;12(1):362. doi: 10.1038/s41467-020-20598-y.
Chia-Lung Wu 1 2 3,  Amanda Dicks 1 2 4,  Nancy Steward 1 2,  Ruhang Tang 1 2,  Dakota B Katz 1 2 4,  Yun-Rak Choi 1 2 5,  Farshid Guilak 6 7 8
Affiliations

Affiliations

  • 1 Dept. of Orthopaedic Surgery, Washington University in Saint Louis, St. Louis, MO, 63110, USA.
  • 2 Shriners Hospitals for Children-St. Louis, St. Louis, MO, 63110, USA.
  • 3 Department of Orthopaedics and Rehabilitation, Center for Musculoskeletal Research, University of Rochester, Rochester, NY, 14627, USA.
  • 4 Dept. of Biomedical Engineering, Washington University in Saint Louis, St. Louis, MO, 63110, USA.
  • 5 Dept. of Orthopaedic Surgery, Yonsei University, Seoul, South Korea.
  • 6 Dept. of Orthopaedic Surgery, Washington University in Saint Louis, St. Louis, MO, 63110, USA. guilak@wustl.edu.
  • 7 Shriners Hospitals for Children-St. Louis, St. Louis, MO, 63110, USA. guilak@wustl.edu.
  • 8 Dept. of Biomedical Engineering, Washington University in Saint Louis, St. Louis, MO, 63110, USA. guilak@wustl.edu.
PMID: 33441552 DOI: 10.1038/s41467-020-20598-y
Abstract

The therapeutic application of human induced pluripotent stem cells (hiPSCs) for cartilage regeneration is largely hindered by the low yield of chondrocytes accompanied by unpredictable and heterogeneous off-target differentiation of cells during chondrogenesis. Here, we combine bulk RNA Sequencing, single cell RNA Sequencing, and bioinformatic analyses, including weighted gene co-expression analysis (WGCNA), to investigate the gene regulatory networks regulating hiPSC differentiation under chondrogenic conditions. We identify specific WNTs and MITF as hub genes governing the generation of off-target differentiation into neural cells and melanocytes during hiPSC chondrogenesis. With heterocellular signaling models, we further show that Wnt signaling produced by off-target cells is responsible for inducing chondrocyte hypertrophy. By targeting WNTs and MITF, we eliminate these cell lineages, significantly enhancing the yield and homogeneity of hiPSC-derived chondrocytes. Collectively, our findings identify the trajectories and molecular mechanisms governing cell fate decision in hiPSC chondrogenesis, as well as dynamic transcriptome profiles orchestrating chondrocyte proliferation and differentiation.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-101464
    ≥98.0%, MITF 抑制剂
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