Identification of Heparan-Sulfate Rich Cells in the Loose Connective Tissues of the Axolotl (Ambystoma mexicanum) with the Potential to Mediate Growth Factor Signaling during Regeneration.
Identification of Heparan-Sulfate Rich Cells in the Loose Connective Tissues of the Axolotl (Ambystoma mexicanum) with the Potential to Mediate Growth Factor Signaling during Regeneration.
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DOI：
10.1007/s40883-019-00140-3
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发表时间：
2020-03
影响因子：
2.6
通讯作者：
Gardiner DM
中科院分区：
文献类型：
--
作者：
Otsuka T;Phan AQ;Laurencin CT;Esko JD;Bryant SV;Gardiner DM
肢体再生是一系列复杂事件的结果，这些事件是由截肢组织衍生的细胞之间的相互作用介导的。在再生早期，这些相互作用是由与神经和伤口上皮相关的生长因子/形态发生素信号传导介导的。这些促再生信号分子的一个共同特性是它们的活性依赖于与细胞外基质 (ECM) 中的硫酸化糖胺聚糖 (GAG)、特别是硫酸乙酰肝素蛋白聚糖 (HSPG) 的相互作用。我们假设蝾螈中有细胞合成特定的 HSPG，在时间和空间上控制生长因子信号传导。在这项研究中，我们鉴定出了蝾螈皮肤 ECM 内的一个细胞亚群，其细胞表面表达高水平的硫酸化 GAG。这些细胞以网格状分布在整个真皮以及肢体组织周围的疏松结缔组织中。这些细胞在再生过程中改变其形态，并且是结缔组织细胞亚群的候选细胞，其功能是在再生过程中形成图案所需的细胞。鉴于它们的高水平 HSPG 表达、星状形态以及它们在整个疏松结缔组织中的分布，我们将这些细胞称为位置信息 GRID（再生细胞、散布细胞和树突细胞）。此外，我们还鉴定了小鼠肢体结缔组织中硫酸化 GAG 高水平表达的细胞，这些细胞可能与蝾螈中的 GRID 细胞具有相同的功能。 GRID 细胞的鉴定可能对再生工程领域的工作具有重要意义。细胞外基质（ECM）对于控制再生过程中细胞间信号传导的空间和时间模式非常重要。在本文中，我们确定了蝾螈皮肤 ECM 内的细胞亚群（GRID 细胞），它们在肢体的疏松结缔组织中形成网格。这些细胞是结缔组织细胞亚群的候选细胞，其功能是在蝾螈肢体再生过程中控制模式形成。我们还在哺乳动物（小鼠）组织中发现了类似的结缔组织细胞群。了解 GRID 细胞的功能将能够通过仿生位置信息网格的工程来控制细胞对内源性生长因子的反应，从而诱导和增强人类再生。
Limb regeneration is the outcome of a complex sequence of events that are mediated by interactions between cells derived from the tissues of the amputated stump. Early in regeneration, these interactions are mediated by growth factor/morphogen signaling associated with nerves and the wound epithelium. One shared property of these proregenerative signaling molecules is that their activity is dependent on interactions with sulfated glycosaminoglycans (GAGs), heparan sulfate proteoglycan (HSPG) in particular, in the extracellular matrix (ECM). We hypothesized that there are cells in the axolotl that synthesize specific HSPGs that control growth factor signaling in time and space. In this study we have identified a subpopulation of cells within the ECM of axolotl skin that express high levels of sulfated GAGs on their cell surface. These cells are dispersed in a grid-like pattern throughout the dermis as well as the loose connective tissues that surround the tissues of the limb. These cells alter their morphology during regeneration, and are candidates for being a subpopulation of connective tissue cells that function as the cells required for pattern-formation during regeneration. Given their high level of HSPG expression, their stellate morphology, and their distribution throughout the loose connective tissues, we refer to these as the positional information GRID (Groups that are Regenerative, Interspersed and Dendritic) cells. In addition, we have identified cells that stain for high levels of expression of sulfated GAGs in mouse limb connective tissue that could have an equivalent function to GRID cells in the axolotl. The identification of GRID cells may have important implications for work in the area of Regenerative Engineering. The extracellular matrix (ECM) is important in controlling the spatial and temporal patterns of cell-cell signaling during regeneration. In this paper we identify a subpopulation of cells (GRID cells) within the ECM of axolotl skin that form a grid throughout the loose connective tissues of the limb. These cells are candidates for being the subpopulation of connective tissue cells that function to control pattern formation during axolotl limb regeneration. We also have identified a similar population of connective tissue cells in mammalian (mouse) tissues. Understanding the function of GRID cells will lead to the ability to induce and enhance regeneration in humans by the engineering of a biomimetic positional information grid to control the response of cells to endogenous growth factors.
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影响因子：
7.3
作者：
Krystel-Whittemore M;Dileepan KN;Wood JG
通讯作者：
Wood JG
影响因子：
2.7
作者：
Makanae, Aki;Mitogawa, Kazumasa;Satoh, Akira
通讯作者：
Satoh, Akira
影响因子：
2.7
作者：
McCusker, Catherine D.;Diaz-Castillo, Carlos;Gardiner, David M.
通讯作者：
Gardiner, David M.
影响因子：
16.6
作者：
Leigh, Nicholas D.;Dunlap, Garrett S.;Whited, Jessica L.
通讯作者：
Whited, Jessica L.
DOI：
10.1073/pnas.1300290110
发表时间：
2013-06-04
影响因子：
11.1
作者：
Godwin, James W.;Pinto, Alexander R.;Rosenthal, Nadia A.
通讯作者：
Rosenthal, Nadia A.