首页> 外文学位 >Bone marrow-derived cells contribute to multilineage reconstitution and blastema stage-specific upregulation of a transient scaffold in regenerating mouse digit tips.
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Bone marrow-derived cells contribute to multilineage reconstitution and blastema stage-specific upregulation of a transient scaffold in regenerating mouse digit tips.

机译:骨髓来源的细胞有助于瞬态支架的多谱系重建和胚泡阶段特异性上调,从而再生小鼠指尖。

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摘要

In 2005, 1.6 million Americans lived with a debilitating amputation and this figure is predicted to double by 2050. But the ability of a mammal to recapitulate a complex limb structure is not impossible. Evidence of children and mice re-growing digit tips following amputation midway through the terminal phalanx (P3) exists. The hallmark of this phenomenon is development of a blastema housing undifferentiated cells capable of being re-programmed to replicate the missing part. Our central goal is to understand specific components of this process for application into pro-scarring injuries.;The mouse digit anatomy is prominently outlined by microfilaments containing ER-TR7, and antigen derived from fibroblast reticular cells (FRCs) of the thymus shown to facilitate intercellular communication to promote lymphoid organogenesis. A unique blastema characteristic is the upregulation of an ER-TR7+ scaffold stemming from half of the blastema population which reverts to its pre-existing pattern after regenerate differentiation concludes. We measured a correlation between ER-TR7 and type III collagen (COL3) at the transcriptional and protein levels both in vitro during induction of ER-TR7 in primary P3 cells and throughout digit regeneration. Co-expression with COL3 sheds light on ER-TR7 identity and allows testing various approaches to manipulation of the scaffold through the better understood mechanism of COL3 regulation. Furthermore, we aimed at determining the origin of ER-TR7+ blastema FRCs.;Using bone marrow (BM) transplantation, we generated eGFP+ BM chimeras to study the fate of BM-derived cells (BMDCs) after amputation based on the hypothesis that in the regenerate, multipotent BMDCs contribute to various cellular phenotypes including FRCs. So we tested co-immunolocalization of eGFP with antigens particular to fibroblastic, hematopoietic, endothelial, osteoblastic, and mural cells. Many BMDCs homed to the injury throughout regeneration. But hematopoietic BMDCs were limited to inflammation whereas mesenchymal BMDCs expanded and were primed as ER--TR7+ FRCs in the P3 BM niche prior to homing to the blastema site, where they amounted to nearly 50% of cells. Moreover, BMDCs differentiated into endothelial, osteoblastic, and smooth muscle subpopulations and although diluted by pre-existing progenitors by the endpoint of regeneration, BMDCs persisted as part of various structures thus contributing to long-term function.
机译:在2005年,有160万人的截肢能力令人沮丧,预计这一数字到2050年将翻一番。但是,哺乳动物再现复杂肢体结构的能力并非没有可能。有证据表明,儿童和小鼠在指节末梢(P3)中途截肢后会重新长出指尖。这种现象的标志是胚泡的形成,该胚泡容纳了未分化的细胞,能够对其进行重新编程以复制缺失的部分。我们的主要目标是了解这一过程的具体组成部分,以应用于瘢痕形成前伤害。包含ER-TR7的微丝和源自胸腺的成纤维细胞网状细胞(FRC)的抗原显着勾勒出小鼠手指的解剖结构细胞间通讯促进淋巴器官发生。胚泡的独特特征是源自一半胚细胞群体的ER-TR7 +支架的上调,在再生分化结束后,ER-TR7 +支架恢复到其先前的模式。我们测量了ER-TR7和III型胶原蛋白(COL3)在转录和蛋白质水平之间的相关性,在体外在原代P3细胞中诱导ER-TR7期间以及整个手指再生过程中。与COL3的共表达阐明了ER-TR7的身份,并允许通过更好地理解的COL3调节机制来测试各种操作支架的方法。此外,我们的目的是确定ER-TR7 +母细胞FRC的起源;使用骨髓(BM)移植,我们生成了eGFP + BM嵌合体,以根据截肢后BM衍生细胞(BMDC)的命运研究假说。再生,多能的BMDC有助于各种细胞表型,包括FRC。因此,我们测试了eGFP与特定于成纤维细胞,造血,内皮,成骨和壁细胞的抗原的共免疫定位。在整个再生过程中,许多BMDC都遭受了伤害。但是造血BMDC只限于炎症,而间充质BMDC则在归巢到胚泡位点之前占P3 BM位点中的ER-TR7 + FRCs,它们占细胞总数的近50%。此外,BMDCs分化为内皮,成骨细胞和平滑肌亚群,尽管通过再生的终点被预先存在的祖细胞稀释,但BMDC作为各种结构的一部分持续存在,从而有助于长期功能。

著录项

  • 作者

    Marrero, Luis Jose.;

  • 作者单位

    Tulane University School of Science and Engineering.;

  • 授予单位 Tulane University School of Science and Engineering.;
  • 学科 Health Sciences Human Development.;Biology Molecular.;Biology Cell.
  • 学位 Ph.D.
  • 年度 2014
  • 页码 208 p.
  • 总页数 208
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 物理化学(理论化学)、化学物理学;
  • 关键词

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