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During development, multipotent cells differentiate through a hierarchy of increasingly restricted progenitor cell types until they realize specialized cell types. A cell differentiation map describes this hierarchy, and inferring these maps is a key challenge in developmental biology. Recent high-throughput single-cell lineage tracing technologies profile lineages and cell types at scale, but lack the resolution to observe the cell type transitions of individual dividing cells. We introduce a formal definition of a cell differentiation map as well as a quantity, the discrepancy, that measures the fit of a map with observed single-cell lineage tracing data. We further develop an algorithm, Carta, that infers an optimal cell differentiation map from single-cell lineage tracing data, balancing the trade-off between the complexity of the cell differentiation map and the discrepancy with the observed data.

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Inferring Cell Differentiation Maps from Lineage Tracing Data

  • 会议论文

  • 发表日期：

    2025年

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  • Palash Sashittal,
  • Richard Y. Zhang,
  • Benjamin K. Law,
  • Henri Schmidt,
  • Alexander Strzalkowski,
  • Adriano Bolondi,
  • Michelle M. Chan,
  • Benjamin J. Raphael

摘要

During development, multipotent cells differentiate through a hierarchy of increasingly restricted progenitor cell types until they realize specialized cell types. A cell differentiation map describes this hierarchy, and inferring these maps is a key challenge in developmental biology. Recent high-throughput single-cell lineage tracing technologies profile lineages and cell types at scale, but lack the resolution to observe the cell type transitions of individual dividing cells. We introduce a formal definition of a cell differentiation map as well as a quantity, the discrepancy, that measures the fit of a map with observed single-cell lineage tracing data. We further develop an algorithm, Carta, that infers an optimal cell differentiation map from single-cell lineage tracing data, balancing the trade-off between the complexity of the cell differentiation map and the discrepancy with the observed data.