肿瘤异质性是癌症的标志，但对其进行机制解析是一个具有挑战性的问题。鲜为人知的是，正常组织内的细胞也是非常多样化的，肝细胞是一个很好的例子，因为它们的空间位置和当地微环境决定了它们的遗传异质性。最近的研究表明，原发性肝肿瘤显示出类似于正常组织中观察到的异质性，为细胞肿瘤的前体和小叶微环境变化如何支持肿瘤形成和侵袭性提供线索。识别控制健康肝脏细胞多样性的原则可能突显出推动肝肿瘤异质性的潜在机制。

Tumor heterogeneity is a hallmark of cancer but a challenging problem to dissect mechanistically. Less recognized is that cells within normal tissues are also remarkably diverse. Hepatocytes are a great example because their spatial positioning and the local microenvironment govern their genetic heterogeneity. Recent studies show that primary liver tumors display heterogeneity similar to that observed in the normal tissue providing clues to the cellular precursor of the tumor and how variations in the lobule microenvironment support tumor formation and aggressiveness. Identifying the principles that control cellular diversity in a healthy liver may highlight potential mechanisms driving hepatic tumor heterogeneity.