A single cell transcriptional atlas of early synovial joint development

Development. 2020 Jul 20;147(14):dev185777. doi: 10.1242/dev.185777.


Synovial joint development begins with the formation of the interzone, a region of condensed mesenchymal cells at the site of the prospective joint. Recently, lineage-tracing strategies have revealed that Gdf5-lineage cells native to and from outside the interzone contribute to most, if not all, of the major joint components. However, there is limited knowledge of the specific transcriptional and signaling programs that regulate interzone formation and fate diversification of synovial joint constituents. To address this, we have performed single cell RNA-Seq analysis of 7329 synovial joint progenitor cells from the developing murine knee joint from E12.5 to E15.5. By using a combination of computational analytics, in situ hybridization and in vitro characterization of prospectively isolated populations, we have identified the transcriptional profiles of the major developmental paths for joint progenitors. Our freely available single cell transcriptional atlas will serve as a resource for the community to uncover transcriptional programs and cell interactions that regulate synovial joint development.

Keywords: Articular cartilage; Chondrocyte; Gdf5; Interzone; Ligament; Meniscus; Single cell RNA-Seq; Synovial joint development; Synovium.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Chondrocytes / cytology
  • Chondrocytes / metabolism
  • Collagen Type II / genetics
  • Collagen Type II / metabolism
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Embryonic Development / genetics
  • Growth Differentiation Factor 5 / deficiency
  • Growth Differentiation Factor 5 / genetics
  • In Situ Hybridization
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism
  • Sequence Analysis, RNA
  • Single-Cell Analysis / methods*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Synovial Membrane / cytology


  • Col2a1 protein, mouse
  • Collagen Type II
  • Gdf5 protein, mouse
  • Growth Differentiation Factor 5
  • SOX9 Transcription Factor
  • Sox9 protein, mouse