Fibroblasts from the Human Skin Dermo-Hypodermal Junction are Distinct from Dermal Papillary and Reticular Fibroblasts and from Mesenchymal Stem Cells and Exhibit a Specific Molecular Profile Related to Extracellular Matrix Organization and Modeling
Fibroblasts from the Human Skin Dermo-Hypodermal Junction are Distinct from Dermal Papillary and Reticular Fibroblasts and from Mesenchymal Stem Cells and Exhibit a Specific Molecular Profile Related to Extracellular Matrix Organization and Modeling
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DOI：
10.3390/cells9020368
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发表时间：
2020-02-01
期刊：
影响因子：
6
通讯作者：
Fortunel, Nicolas O.
中科院分区：
文献类型：
--
作者：
Haydont, Valerie;Neiveyans, Veronique;Fortunel, Nicolas O.
人类皮肤真皮含有成纤维细胞亚群，由于它们在细胞外基质 (ECM) 生物学中的作用，其表征至关重要。本研究研究了位于真皮深层和皮下组织边界的成纤维细胞的特性，即真皮-皮下交界处成纤维细胞（F-DHJ），并将其与真皮中间网状层（Fr）和浅层真皮乳头层（Fp）成纤维细胞进行了比较。 F-DHJ 与 Fr 和 Fp 细胞的不同之处在于，F-DHJ 具有更广泛的分化为中胚层谱系的潜力，并且在整合到三维真皮等效物中时缺乏收缩性。 F-DHJ 的转录组谱在参与 ECM 合成加工和“组织骨架”组织的基因表达中表现出特异性。根据转录组数据，ECM 蛋白（尤其是腱蛋白 C）在网状真皮和真皮-皮下交界区之间的分布不同，这在正常成人皮肤中得到记录。最后，使用全基因组转录组分析来评估 F-DHJ 与两种真皮成纤维细胞群（Fp 和 Fr）以及与对应于五个组织来源（骨髓、脂肪、羊膜、绒毛膜和脐带）的间充质干细胞（MSC）的分子接近性。该比较分析将包括 F-DHJ 在内的三种皮肤成纤维细胞类型分类为与五个 MSC 样本来源明显不同的组。
Human skin dermis contains fibroblast subpopulations in which characterization is crucial due to their roles in extracellular matrix (ECM) biology. This study investigates the properties of fibroblasts localized at the frontier of deep dermis and hypodermis, i.e., dermo-hypodermal junction fibroblasts (F-DHJ), which were compared to intermediate reticular dermis (Fr) and superficial papillary dermis (Fp) fibroblasts. F-DHJ differed from Fr and Fp cells in their wider potential for differentiation into mesodermal lineages and in their absence of contractility when integrated in a three-dimensional dermal equivalent. The transcriptomic profile of F-DHJ exhibited specificities in the expression of genes involved in ECM synthesis-processing and "tissue skeleton" organization. In accordance with transcriptome data, ECM proteins, notably Tenascin C, distributions differed between the reticular dermis and the dermo-hypodermal junction areas, which was documented in normal adult skin. Finally, genome-wide transcriptome profiling was used to evaluate the molecular proximity of F-DHJ with the two dermal fibroblast populations (Fp and Fr) and with the mesenchymal stem cells (MSCs) corresponding to five tissue origins (bone marrow, fat, amnion, chorion, and cord). This comparative analysis classified the three skin fibroblast types, including F-DHJ, as a clearly distinct group from the five MSC sample origins.