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<p>Human pluripotent stem cells offer a scalable platform to study genetic and signalling mechanisms governing cell lineage decisions during differentiation. Genome-wide and single-cell transcriptomics technologies likewise offer high-throughput analysis of heterogeneous cell differentiation states. While <i>in vivo</i> development has been extensively characterised using these technologies, there remains a need for comprehensive single-cell transcriptomic profiling of stem cell differentiation from pluripotency. Understanding gene expression changes governing differentiation <i>in vitro</i> is key to developing high fidelity differentiation protocols and understanding fundamental mechanisms of development. We generated a single-cell RNA sequencing time course to study the role of developmental signalling pathways on multilineage diversification from pluripotency <i>in vitro</i>. The combined dataset of over 60,000 cells spans cell types from a time course of differentiation across all germ layers, ranging from gastrulation cell states to progenitor and committed cell types. These data provide a diverse benchmarking reference point to compare against <i>in vivo</i> development and advance understanding of signalling regulation of differentiation, providing insights into protocol development, drug screening, and regenerative medicine applications.</p>

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A pluripotent stem cell atlas of multilineage differentiation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月15日

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  • Sophie Shen,
  • Tessa Werner,
  • Han Sheng Chiu,
  • Xiaoli Chen,
  • Quan Nguyen,
  • Nathan J. Palpant

摘要

Human pluripotent stem cells offer a scalable platform to study genetic and signalling mechanisms governing cell lineage decisions during differentiation. Genome-wide and single-cell transcriptomics technologies likewise offer high-throughput analysis of heterogeneous cell differentiation states. While in vivo development has been extensively characterised using these technologies, there remains a need for comprehensive single-cell transcriptomic profiling of stem cell differentiation from pluripotency. Understanding gene expression changes governing differentiation in vitro is key to developing high fidelity differentiation protocols and understanding fundamental mechanisms of development. We generated a single-cell RNA sequencing time course to study the role of developmental signalling pathways on multilineage diversification from pluripotency in vitro. The combined dataset of over 60,000 cells spans cell types from a time course of differentiation across all germ layers, ranging from gastrulation cell states to progenitor and committed cell types. These data provide a diverse benchmarking reference point to compare against in vivo development and advance understanding of signalling regulation of differentiation, providing insights into protocol development, drug screening, and regenerative medicine applications.