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

人类皮肤真皮-皮下交界处的成纤维细胞与真皮乳头状和网状成纤维细胞以及间充质干细胞不同,并表现出与细胞外基质组织和重塑相关的特定分子特征。

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作者:Valérie Haydont ,Véronique Neiveyans ,Philippe Perez ,Élodie Busson ,JeanJacques Lataillade ,Daniel Asselineau ,Nicolas O Fortunel

Abstract

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. Keywords: Tenascin C (TNC); dermo-hypodermal junction; extracellular matrix (ECM); fibroblasts; human dermis; mesenchymal stem cells (MSCs); papillary fibroblasts (Fp); reticular fibroblasts (Fr).

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