Novel Lineage-Tracing System to Identify Site-Specific Ectopic Bone Precursor Cells
Chase A. Pagani, Amanda K. Huber, Charles Hwang, Simone Marini, Karthik Padmanabhan, Nicholas Livingston, Johanna Nunez, Yuxiao Sun, Nicole Edwards, Yu‐Hao Cheng, Noelle D. Visser, Pauline Yu, Nicole Patel, Joseph A. Greenstein, Husain Rasheed, Reagan Nelson, Karen Kessel, Kaetlin Vasquez, Amy L. Strong, Geoffrey E. Hespe, Jane Y. Song, Deneen M. Wellik, Benjamin Lévi
Abstract
;ROSA26-LSL-TdTomato), we found that Hoxa11-lineage cells represent HO progenitors specifically in the zeugopod. Bioinformatic single-cell transcriptomic and epigenomic analyses showed Hoxa11-lineage cells are regionally restricted mesenchymal cells that, after injury, gain the potential to undergo differentiation toward chondrocytes, osteoblasts, and adipocytes. This study identifies Hoxa11-lineage cells as zeugopod-specific ectopic bone progenitors and elucidates the fate specification and multipotency that mesenchymal cells acquire after injury. Furthermore, this highlights homeobox patterning genes as useful tools to trace region-specific progenitors and enable location-specific gene deletion.