Ji Fulong, Liu Yong, Shi Jinsong, Liu Chunxiang, Fu Siqi, Wang Heng, Ren Bingbing, Mi Dong, Gao Shan, Sun Daqing
Department of Paediatric Surgery, Tianjin Medical University General Hospital, Tianjin, China.
College of Life Sciences, Nankai University, Tianjin, China.
Front Cell Dev Biol. 2022 Jul 5;10:916045. doi: 10.3389/fcell.2022.916045. eCollection 2022.
A cavernous hemangioma, well-known as vascular malformation, is present at birth, grows proportionately with the child, and does not undergo regression. Although a cavernous hemangioma has well-defined histopathological characteristics, its origin remains controversial. In the present study, we characterized the cellular heterogeneity of a cavernous hemangioma using single-cell RNA sequencing (scRNA-seq). The main contribution of the present study is that we discovered a large number of embryonic mesenchymal stem cells (MSCs) in a cavernous hemangioma and proposed that cavernous hemangiomas may originate from embryonic MSCs. Further analysis of the embryonic MSCs revealed that: 1) proinflammatory cytokines and related genes , , , , and are significantly involved in the MSC-induced immune responses in cavernous hemangiomas; 2) is up-regulated in the embryonic MSC apoptosis induced by proinflammatory cytokines; 3) the UCHL1-induced apoptosis of MSCs may play an important role in the MSC-induced immune responses in cavernous hemangiomas; and 4) can be used as a marker gene to detect embryonic MSCs at different apoptosis stages. In addition to MSCs, ECs, macrophages, T lymphocytes and NKCs were intensively investigated, revealing the genes and pathways featured in cavernous hemangiomas. The present study revealed the origin of cavernous hemangiomas and reported the marker genes, cell types and molecular mechanisms, which are associated with the origin, formation, progression, diagnosis and therapy of cavernous hemangiomas. The better understanding of the MSC-induced immune responses in benign tumours helps to guide future investigation and treatment of embryonic MSC-caused tumours. Our findings initiated future research for the rediscovery of MSCs, cancers/tumours and the UCHL1-induced apoptosis.
海绵状血管瘤，众所周知为血管畸形，在出生时就存在，随儿童生长而按比例生长，且不会消退。尽管海绵状血管瘤具有明确的组织病理学特征，但其起源仍存在争议。在本研究中，我们使用单细胞RNA测序（scRNA-seq）对海绵状血管瘤的细胞异质性进行了表征。本研究的主要贡献在于，我们在海绵状血管瘤中发现了大量胚胎间充质干细胞（MSC），并提出海绵状血管瘤可能起源于胚胎MSC。对胚胎MSC的进一步分析表明：1）促炎细胞因子和相关基因、、、、和在海绵状血管瘤中MSC诱导的免疫反应中显著参与；2）在促炎细胞因子诱导的胚胎MSC凋亡中上调；3）UCHL1诱导的MSC凋亡可能在海绵状血管瘤中MSC诱导的免疫反应中起重要作用；4）可作为检测不同凋亡阶段胚胎MSC的标记基因。除了MSC外，还对内皮细胞（EC）、巨噬细胞、T淋巴细胞和自然杀伤细胞（NKC）进行了深入研究，揭示了海绵状血管瘤的特征基因和信号通路。本研究揭示了海绵状血管瘤的起源，并报道了与海绵状血管瘤的起源、形成、进展、诊断和治疗相关的标记基因、细胞类型和分子机制。对良性肿瘤中MSC诱导的免疫反应的更好理解有助于指导未来对胚胎MSC引起的肿瘤的研究和治疗。我们的发现开启了对MSC、癌症/肿瘤以及UCHL1诱导的凋亡重新发现的未来研究。
