Post natal expression of Prx1 labels appendicular restricted progenitor cell populations of multiple tissues

Abstract

Currently, there is no consensus whether there is a single or multiple postnatal stem cell population(s) that contribute to skeletal homeostasis and postnatal bone formation. A known population of cells that express Prx1 contributes to postnatal bone formation. Prx1 expression also connotes calvaria and appendicular tissues during embryonic development. A transgenic tamoxifen inducible Prx1 reporter mouse was used for lineage tracking, to characterize the postnatal contribution of Prx1 expressing cells in skeletal homeostasis and bone formation. Under homeostatic conditions Prx1 labeling gave rise to a transient yet rapid turnover cell population at the periosteal and endosteal surfaces, along muscle fibers, and within the medial layers of vessels both within the muscle and marrow compartments of the appendicular skeleton. Fracture and ectopic bone formation of both fore and hind limbs showed recruitment and expansion of Prx1‐derived cells in newly formed bone tissues. Prx1 labeled cells were limited or absent at axial skeletal sites during both homeostasis and after induction of bone formation. Last, Prx1‐derived cells differentiated into multiple cell lineages including vascular smooth muscle, adipose, cartilage, and bone cells. These results show that Prx1 expression retained its embryonic tissue specification and connotes a stem/progenitor cell populations of mesenchymal tissue progenitors.

Prx1 cell subpopulations identified in various tissues with diverse quiescence and activation ability following fracture and BMP2 stimulation

“…Within the nonhematopoietic population isolated from the muscle, periosteum and bone marrow, the percentage of Prx1 cells were 33.22 ± 9.70%, 5.58 ± 1.70%, and 0.58 ± 0.13% (Figure 4B). Overall, Prx1-expressing cells have the highest fraction in skeletal muscle, which aligns with the observations we obtained from our previous histological analysis (Bragdon et al, 2022).…”

“…Advances with genetic mouse models have revealed several markers that can be used to define various populations of SSCs, including Nestin, LepR, Mx1, αSMA, Periostin, Cathespin K, Cxcl12, Prx1 (Méndez-Ferrer et al, 2010;Park et al, 2012;Greenbaum et al, 2013;Zhou et al, 2014;Debnath et al, 2018;Duchamp de Lageneste et al, 2018). Published work along with our studies showed Prx1 expressing cells connote a multi-potential postnatal SSC population that retained its embryonic tissue specification, localized to multiple sites such as bone marrow, periosteum, and muscle within the appendicular regions and contributes to homeostatic maintenance, fracture repair, and HO (Batista et al, 2019;Julien et al, 2021;Bragdon et al, 2022).…”

“…This overexpression is observed in all three tissues where bone marrow shows the most significant difference while muscle to a much less extent. It implies that muscle-derived skeletal stem/progenitor cells do not demonstrate osteogenic capacity under homeostasis unless they receive environmental signals, where bone marrow and periosteum counterparts are constantly turned over at a higher rate and involved in homeostatic maintenance of the bone tissue as previously suggested (Park et al, 2012;Bragdon et al, 2022).…”

“…The wild type C57BL/6J (B6, Jackson Laboratory, Stock 000,664) and transgenic mice, Prx1-CreER/Ai14/Rag1, were used for this study. The Prx1-CreER/Ai14/Rag1 mice was previously described ( Bragdon et al, 2022 ), briefly the strain was established by crossing the Ai14 (007,914, B6. Cg-Gt (ROSA)26Sor tm14(CAG-tdTomato)Hze /J), with Prx1-Cre/ERT2-EGFP (provided by Dr. Shunichi Murakami ( Kawanami et al, 2009 )) and with the Rag1 (002,216, B6.129S7-Rag1 tm1/MOM /J).…”

Differential regulation of skeletal stem/progenitor cells in distinct skeletal compartments

“…Consistently, most Prx1 + SSPCs are present in the long bone periosteum during embryonic and postnatal development. Prx1 + cells are present during embryonic development restricted to the mesoderm which becomes mesenchymal cells postnatally without losing their embryonic tissue specification and thus have SSPC properties (Du et al, 2013;Bragdon et al, 2022). These pnPrx1 + P-SSPCs are known to inhibit adipogenesis by activating TGFβ signaling (Du et al, 2013).…”