Abstract：
Human pluripotent stem (hPS) cells can, in theory, be differentiated into any cell type, making them a powerful in vitro model for human biology. Recent technological advances have facilitated large-scale hPS cell studies that allow investigation of the genetic regulation of molecular phenotypes and their contribution to high-order phenotypes such as human disease. Integrating hPS cells with single-cell sequencing makes identifying context-dependent genetic effects during cell development or upon experimental manipulation possible. Here we discuss how the intersection of stem cell biology, population genetics and cellular genomics can help resolve the functional consequences of human genetic variation. We examine the critical challenges of integrating these fields and approaches to scaling them cost-effectively and practically. We highlight two areas of human biology that can particularly benefit from population-scale hPS cell studies, elucidating mechanisms underlying complex disease risk loci and evaluating relationships between common genetic variation and pharmacotherapeutic phenotypes.
摘要：
人类多能干细胞（hPS）可以，理论上,分化为任何细胞类型，使它们成为人类生物学的强大体外模型。最近的技术进步促进了大规模的hPS细胞研究，这些研究允许研究分子表型的遗传调控及其对人类疾病等高阶表型的贡献。将hPS细胞与单细胞测序整合使得在细胞发育期间或在实验操作后识别环境依赖性遗传效应成为可能。在这里，我们讨论干细胞生物学的交叉，群体遗传学和细胞基因组学可以帮助解决人类遗传变异的功能后果。我们研究了整合这些领域和方法的关键挑战，以经济有效地和实际地扩展它们。我们强调了人类生物学的两个领域，这些领域可以特别受益于人群规模的hPS细胞研究，阐明复杂疾病风险位点的潜在机制，并评估常见遗传变异与药物治疗表型之间的关系。
