Single cell analysis of human foetal liver captures the transcriptional profile of hepatobiliary hybrid progenitors
Single cell analysis of human foetal liver captures the transcriptional profile of hepatobiliary hybrid progenitors
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DOI：
10.1038/s41467-019-11266-x
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发表时间：
2019-07-26
影响因子：
16.6
通讯作者：
Rashid, S. Tamir
中科院分区：
文献类型：
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作者：
Segal, Joe M.;Kent, Deniz;Rashid, S. Tamir
肝实质由肝细胞和胆管上皮细胞（BECs）组成。关于人肝实质组织在胚胎发育、体内平衡或修复过程中的细胞起源存在争议。在这里，我们使用单细胞RNA测序报告了人类胎儿肝脏中肝胆混合祖细胞（HHyP）群体的存在。HHyPs在解剖学上局限于胎儿肝脏的导管板，并保持与胎儿肝细胞、成熟肝细胞和成熟BECs不同的转录谱。此外，新分离的胎儿和成人肝脏EpCAM（+）群体中的分子异质性确定了肝脏和胆道谱系潜力的不同基因表达特征。最后，我们用流式细胞术分离胎儿HHyPs，并在体内确认其杂交祖细胞表型。我们的研究表明，先前在小鼠中发现的肝胆祖细胞也存在于人类中，并且可以通过不同的基因表达谱与其他实质细胞群体（包括成熟的BECs）区分开来。
The liver parenchyma is composed of hepatocytes and bile duct epithelial cells (BECs). Controversy exists regarding the cellular origin of human liver parenchymal tissue generation during embryonic development, homeostasis or repair. Here we report the existence of a hepatobiliary hybrid progenitor (HHyP) population in human foetal liver using single-cell RNA sequencing. HHyPs are anatomically restricted to the ductal plate of foetal liver and maintain a transcriptional profile distinct from foetal hepatocytes, mature hepatocytes and mature BECs. In addition, molecular heterogeneity within the EpCAM(+) population of freshly isolated foetal and adult human liver identifies diverse gene expression signatures of hepatic and biliary lineage potential. Finally, we FACS isolate foetal HHyPs and confirm their hybrid progenitor phenotype in vivo. Our study suggests that hepatobiliary progenitor cells previously identified in mice also exist in humans, and can be distinguished from other parenchymal populations, including mature BECs, by distinct gene expression profiles.