State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine. 79 Qingchun Rd., Hangzhou, 310003. China.
Clinical Medical Laboratory, Tongde Hospital of Zhejiang Province. 234 Gucui Rd., Hangzhou, 310012. China.
Int J Med Sci. 2020 Jan 14;17(2):263-273. doi: 10.7150/ijms.36255. eCollection 2020.
: Human bone marrow mesenchymal stem cell-derived hepatocyte-like cells (hBMSC-HLCs) are a promising alternative for primary human hepatocytes (HHs) for treating liver disease. However, the molecular characteristics of HLCs remain unclear. Here, we aimed to clarify the transcriptome characteristics of hBMSC-HLCs for future clinical application. : hBMSCs were isolated from the bone marrow of healthy volunteers and differentiated into hepatocytes. mRNA sequencing was used in the transcriptome profiling of hBMSC-HLCs, with hBMSCs and HHs as controls. : hBMSC-HLCs exhibited a polygonal morphology, glycogen accumulation and albumin expression. A total of 630 upregulated and 1082 downregulated genes were observed in hBMSC-HLCs and HHs compared with undifferentiated hBMSCs. The upregulated genes were mainly involved in hepatic metabolism and inflammatory and immune responses. The downregulated genes were mainly associated with stem cell characteristics (multipotent differentiation, cell cycle regulation, etc.). Confirmatory qRT-PCR of 9 upregulated and 9 downregulated genes with log2 fold changes > 5 showed similar results. transdifferentiation of hBMSCs in pigs with fulminant hepatic failure confirmed the similarly upregulated expression of 5 hepatogenic genes ( and ), showing a 150-fold change in liver tissues at 7 days after hBMSC transplantation. These 5 genes mainly contributed to liver metabolism and inflammation. : hBMSC-HLCs possess a hepatic transcriptome profile and express hepatic-specific genes and , which might be useful for future clinical applications. The five upregulated genes identified herein could be potential biomarkers for the characterization of hBMSC-HLCs.
人骨髓间充质干细胞来源的肝细胞样细胞（hBMSC-HLCs）是治疗肝脏疾病的原代人肝细胞（HHs）的有前途的替代品。然而，HLCs 的分子特征尚不清楚。在这里，我们旨在阐明 hBMSC-HLCs 的转录组特征，以便将来用于临床应用。
从健康志愿者的骨髓中分离 hBMSCs 并分化为肝细胞。使用 mRNA 测序对 hBMSC-HLCs 的转录组图谱进行分析，以 hBMSCs 和 HHs 作为对照。
hBMSC-HLCs 呈多角形形态，有糖原积累和白蛋白表达。与未分化的 hBMSCs 相比，hBMSC-HLCs 和 HHs 中观察到 630 个上调基因和 1082 个下调基因。上调基因主要参与肝脏代谢以及炎症和免疫反应。下调基因主要与干细胞特征（多能分化、细胞周期调节等）有关。对 9 个上调基因和 9 个下调基因（log2 倍数变化>5）进行的 9 个上调和 9 个下调基因的 qRT-PCR 验证显示出相似的结果。用猪暴发性肝衰竭进行的 hBMSC 转分化实验证实了 5 个肝生成基因（、和）的表达同样上调，在 hBMSC 移植后 7 天的肝脏组织中变化了 150 倍。这 5 个基因主要参与肝脏代谢和炎症。
hBMSC-HLCs 具有肝脏转录组特征，并表达肝脏特异性基因和，这可能对未来的临床应用有用。本文鉴定的 5 个上调基因可能是 hBMSC-HLCs 特征的潜在生物标志物。
