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

被引：28

作者：

Pagani, Chase A. ^{[1
]}

Huber, Amanda K. ^{[2
]}

Hwang, Charles ^{[2
]}

Marini, Simone ^{[2
]}

Padmanabhan, Karthik ^{[3
]}

Livingston, Nicholas ^{[1
]}

Nunez, Johanna ^{[1
]}

Sun, Yuxiao ^{[1
]}

Edwards, Nicole ^{[2
]}

Cheng, Yu-Hao ^{[4
]}

Visser, Noelle ^{[2
]}

Yu, Pauline ^{[2
]}

Patel, Nicole ^{[2
]}

Greenstein, Joseph A. ^{[2
]}

Rasheed, Husain ^{[2
]}

Nelson, Reagan ^{[2
]}

Kessel, Karen ^{[2
]}

Vasquez, Kaetlin ^{[2
]}

Strong, Amy L. ^{[2
]}

Hespe, Geoffrey E. ^{[2
]}

Song, Jane Y. ^{[5
]}

Wellik, Deneen M. ^{[5
]}

Levi, Benjamin ^{[1
]}

机构：

[1] Univ Texas Southwestern, Dept Surg, Ctr Organogenesis & Trauma, 6000 Harry Hines Blvd, Dallas, TX 75235 USA

[2] Univ Michigan, Dept Surg, Sect Plast Surg, Ann Arbor, MI 48109 USA

[3] Univ Michigan, BRCF Epigen Core, Ann Arbor, MI 48109 USA

[4] Johns Hopkins Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA

[5] Univ Wisconsin, Dept Cell & Regenerat Biol, Madison, WI 53705 USA

来源：

STEM CELL REPORTS | 2021年 / 16卷 / 03期

关键词：

HETEROTOPIC OSSIFICATION; PROGENITOR CELLS; STEM-CELLS; CONTRIBUTE; EXPRESSION; SCLERAXIS; DIFFERENTIATION; IDENTIFICATION; INTEGRATION; INHIBITION;

D O I：

10.1016/j.stemcr.2021.01.011

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Heterotopic ossification (HO) is a form of pathological cell-fate change of mesenchymal stem/precursor cells (MSCs) that occurs following traumatic injury, limiting range of motion in extremities and causing pain. MSCs have been shown to differentiate to form bone; however, their lineage and aberrant processes after trauma are not well understood. Utilizing a well-established mouse HO model and inducible lineage-tracing mouse (Hoxa11-CreER(T2);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.

引用

页码：626 / 640

页数：15

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