Lineage tracing of resident tendon progenitor cells during growth and natural healing.
Lineage tracing of resident tendon progenitor cells during growth and natural healing.
复制标题
DOI：
10.1371/journal.pone.0096113
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Rowe DW
中科院分区：
文献类型：
--
作者：
Dyment NA;Hagiwara Y;Matthews BG;Li Y;Kalajzic I;Rowe DW
与胚胎发育过程不同，有助于出生后肌腱生长和自然愈合的组织驻留祖细胞的特性很差。因此，我们利用1）由α平滑肌肌动蛋白（SMACreERT 2）驱动的可诱导Cre，其鉴定间充质祖细胞，2）由生长和分化因子5（GDF 5Cre）驱动的组成型活性Cre，其是关节凝聚的关键调节因子，与3）Ai 9 Cre报告基因组合以永久标记SMA 9和GDF 5 -9群体及其后代。在生长期小鼠中，在腱周结构中发现SMA 9+细胞，在肌腱中间质和肌腱连接处发现巩膜轴阳性（ScxGFP+）细胞。肌腱中间物质内的祖细胞被瞬时标记，因为它们从第2天到第21天显示出4倍扩增，但到第70天降低到基线水平。在膝关节的肌腱附着点或韧带中未发现SMA 9+细胞，表明其来源不同。与SMA 9群体相反，GDF 5 -9+细胞从骨延伸通过附着点并进入肌腱中间体的一部分。在整个韧带长度上也发现了GDF 5 -9+细胞，表明有助于肌腱和韧带的祖细胞存在显著变化。肌腱损伤后，SMA 9+腱旁细胞是愈合反应的主要贡献者。SMA 9+细胞在1周时在缺损空间上延伸，并在2周时分化成ScxGFP+细胞，这与腱旁桥中胶原信号增加相一致。因此，SMA 9标记的细胞代表了一种独特的祖细胞来源，其在生长和自然愈合期间有助于肌腱中间体、腱旁和肌腱连接，而GDF 5祖细胞有助于肌腱附着点和韧带发育。了解调节这些祖细胞扩增和分化的机制可能对改善未来的修复策略至关重要。
Unlike during embryogenesis, the identity of tissue resident progenitor cells that contribute to postnatal tendon growth and natural healing is poorly characterized. Therefore, we utilized 1) an inducible Cre driven by alpha smooth muscle actin (SMACreERT2), that identifies mesenchymal progenitors, 2) a constitutively active Cre driven by growth and differentiation factor 5 (GDF5Cre), a critical regulator of joint condensation, in combination with 3) an Ai9 Cre reporter to permanently label SMA9 and GDF5-9 populations and their progeny. In growing mice, SMA9+ cells were found in peritendinous structures and scleraxis-positive (ScxGFP+) cells within the tendon midsubstance and myotendinous junction. The progenitors within the tendon midsubstance were transiently labeled as they displayed a 4-fold expansion from day 2 to day 21 but reduced to baseline levels by day 70. SMA9+ cells were not found within tendon entheses or ligaments in the knee, suggesting a different origin. In contrast to the SMA9 population, GDF5-9+ cells extended from the bone through the enthesis and into a portion of the tendon midsubstance. GDF5-9+ cells were also found throughout the length of the ligaments, indicating a significant variation in the progenitors that contribute to tendons and ligaments. Following tendon injury, SMA9+ paratenon cells were the main contributors to the healing response. SMA9+ cells extended over the defect space at 1 week and differentiated into ScxGFP+ cells at 2 weeks, which coincided with increased collagen signal in the paratenon bridge. Thus, SMA9-labeled cells represent a unique progenitor source that contributes to the tendon midsubstance, paratenon, and myotendinous junction during growth and natural healing, while GDF5 progenitors contribute to tendon enthesis and ligament development. Understanding the mechanisms that regulate the expansion and differentiation of these progenitors may prove crucial to improving future repair strategies.
登录
查看更多内容
影响因子：
5.2
作者：
Grcevic, Danka;Pejda, Slavica;Matthews, Brya G.;Repic, Dario;Wang, Liping;Li, Haitao;Kronenberg, Mark S.;Jiang, Xi;Maye, Peter;Adams, Douglas J.;Rowe, David W.;Aguila, Hector L.;Kalajzic, Ivo
通讯作者：
Kalajzic, Ivo
平铺 3D 显微图像采集的全局最佳拼接。
DOI：
10.1093/bioinformatics/btp184
发表时间：
2009-06-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Preibisch S;Saalfeld S;Tomancak P
通讯作者：
Tomancak P
影响因子：
64.8
作者：
Buczacki, Simon J. A.;Zecchini, Heather Ireland;Winton, Douglas J.
通讯作者：
Winton, Douglas J.
影响因子：
82.9
作者：
Bi, Yanming;Ehirchiou, Driss;Young, Marian F.
通讯作者：
Young, Marian F.
影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
通讯作者：
Zeng H