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

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2021 Feb 19

PMID 33606989

Citations 19

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

Affiliations

Soon will be listed here.

Abstract

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;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.

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