Novel Lineage-Tracing System to Identify Site-Specific Ectopic Bone Precursor Cells

• DOI: 10.1016/j.stemcr.2021.01.011
• Publication Date: 2021-02-21T17:29:07Z
• Authors: Chase A. Pagani; Amanda K. Huber; Charles Hwang; Simone Marini; Karthik Padmanabhan; Nicholas Livingston; Johanna Nunez; Yuxiao Sun; Nicole Edwards; Yu-Hao Cheng; Noelle 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 Levi
• Keywords: Lineage (genetic); Cell fate determination; Ectopic expression; Progenitor

Heterotopic ossification (HO) is a form of pathological cell-fate change mesenchymal stem/precursor cells (MSCs) that occurs following traumatic injury, limiting range motion in extremities and causing pain. MSCs have been shown to differentiate bone; however, their lineage aberrant processes after trauma are not well understood. Utilizing well-established mouse HO model inducible lineage-tracing (Hoxa11-CreERT2;ROSA26-LSL-TdTomato), we found Hoxa11-lineage represent progenitors specifically the zeugopod. Bioinformatic single-cell transcriptomic epigenomic analyses showed regionally restricted that, gain potential undergo differentiation toward chondrocytes, osteoblasts, adipocytes. This study identifies as zeugopod-specific ectopic bone elucidates fate specification multipotency acquire injury. Furthermore, this highlights homeobox patterning genes useful tools trace region-specific enable location-specific gene deletion.