Choi Rhea, Goncalves Stefania, Durante Michael A, Goldstein Bradley J
Medical Scientist Training Program University of Miami Miller School of Medicine Miami Florida USA.
Department of Otolaryngology University of Miami Miller School of Medicine Miami Florida USA.
Laryngoscope Investig Otolaryngol. 2020 Oct 10;5(6):975-982. doi: 10.1002/lio2.472. eCollection 2020 Dec.
Mesenchymal stem cells (MSCs), classically expanded in culture from bone marrow, are of broad interest to the regenerative medicine community. Human nasal turbinate mesenchymal-like stem cell cultures have also been described, defined by an in vitro phenotype similar to bone marrow MSCs. Nonetheless, the identity in vivo of the cells that give rise to nasal MSC-like cultures remains unclear, and these cells are often suggested to be related to olfactory lineages. Here, we sought to define the in vivo phenotype of human nasal MSC-like cells.
Human turbinate tissue samples were used for RNA and immunohistochemical analysis. We also analyzed a recently published single cell RNA-sequencing dataset from adult human olfactory and respiratory mucosa samples from our lab, to focus on cell populations expressing MSC markers. Immunochemistry was performed to stain turbinate sections and nasal MSC cultures for selected markers.
While there is no single MSC-specific gene, we identified a human nasal mucosal cell population in vivo that uniquely expressed transcripts characteristic of typical MSC cultures, including ENG (CD105), NES, and CD34, and lacked expression of other transcripts associated with surface epithelia. The expression of transcription factors such as SOX17, EBF1, and FOXP1 suggests cells in the MSC-like cluster maintain an ability to direct cell fate, consistent with the behavior of nasal MSC-like cells in vitro. SOX17 was found to be uniformly expressed by nasal MSC cultures, consistent with the in vivo data. Immunohistochemistry of human nasal tissue samples indicated that ENG, CD34, and SOX17 expression localized selectively to cells surrounding blood vessels in the lamina propria.
Our findings provide evidence that the in vivo origin of nasal MSC-like cultures is likely a vascular or pericyte population, rather than cells related to the olfactory neuronal lineage.
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间充质干细胞（MSCs）传统上是从骨髓中培养扩增而来，受到再生医学领域的广泛关注。人类鼻甲间充质样干细胞培养物也有相关报道，其体外表型与骨髓间充质干细胞相似。然而，产生鼻甲间充质样培养物的细胞在体内的身份仍不清楚，并且这些细胞常被认为与嗅觉谱系相关。在此，我们试图明确人类鼻甲间充质样细胞的体内表型。
使用人类鼻甲组织样本进行RNA和免疫组织化学分析。我们还分析了我们实验室最近发表的来自成年人类嗅觉和呼吸黏膜样本的单细胞RNA测序数据集，以聚焦于表达间充质干细胞标志物的细胞群体。进行免疫化学染色以检测鼻甲切片和鼻甲间充质干细胞培养物中的选定标志物。
虽然没有单一的间充质干细胞特异性基因，但我们在体内鉴定出一种人类鼻黏膜细胞群体，其独特地表达典型间充质干细胞培养物的特征性转录本，包括ENG（CD105）、NES和CD34，并且缺乏与表面上皮相关的其他转录本的表达。转录因子如SOX17、EBF1和FOXP1的表达表明间充质样簇中的细胞保持着指导细胞命运的能力，这与体外鼻甲间充质样细胞的行为一致。发现SOX17在鼻甲间充质干细胞培养物中均匀表达，与体内数据一致。人类鼻组织样本的免疫组织化学表明，ENG、CD34和SOX17的表达选择性地定位于固有层中血管周围的细胞。
我们的研究结果提供了证据，表明鼻甲间充质样培养物的体内起源可能是血管或周细胞群体，而不是与嗅觉神经元谱系相关的细胞。
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