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<p>Evolution has used cell–cell communication as a strategy to coordinate organ development, enabling the reproducible generation of intricate structures. Classically, these interactions have been studied one at a time in model organisms, limiting our understanding of how cellular interplay coordinates human development. We investigated human kidney development using single-cell RNA sequencing and spatial transcriptomics, analyzing over 700,000 cells. By mapping gene expression and differentiation trajectories in space, we define the spatial organization of kidney development. Our analysis revealed unrecognized plasticity, showing that cell fate established during early patterning can be later revised. This plasticity provides a potential mechanism for how cell fate is robustly established in complex patterned tissues. Additionally, through a genome-wide, spatially aware cell–cell interaction analysis, we link localized ligand signals to cell fate decisions. We also define biologically meaningful cellular neighborhoods based on aggregated extracellular cues, providing a blueprint to understand the coordination of human development at scale.</p>

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Single-cell spatial mapping of human kidney development implicates the microenvironment in guiding cell fate decisions

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月30日

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  • Jonathan Levinsohn,
  • Samuel Grindel,
  • Bernhard Dumoulin,
  • Amin Abedini,
  • Carolina Conte,
  • Aria Zheyuan Huang,
  • Rena Levin-Klein,
  • Boaz Weisz,
  • Grace Rabinowitz,
  • Andi M. Bergeson,
  • Eunji Ha,
  • Konstantin A. Klötzer,
  • Nancy Zhang,
  • Paul Titchenell,
  • Mingyao Li,
  • Joo-Seop Park,
  • Juan Pablo Arroyo,
  • Laura S. Finn,
  • Kotaro Sasaki,
  • Pazit Beckerman,
  • Oren Pleniceanu,
  • Paola Romagnani,
  • Alex J. Hughes,
  • Katalin Susztak

摘要

Evolution has used cell–cell communication as a strategy to coordinate organ development, enabling the reproducible generation of intricate structures. Classically, these interactions have been studied one at a time in model organisms, limiting our understanding of how cellular interplay coordinates human development. We investigated human kidney development using single-cell RNA sequencing and spatial transcriptomics, analyzing over 700,000 cells. By mapping gene expression and differentiation trajectories in space, we define the spatial organization of kidney development. Our analysis revealed unrecognized plasticity, showing that cell fate established during early patterning can be later revised. This plasticity provides a potential mechanism for how cell fate is robustly established in complex patterned tissues. Additionally, through a genome-wide, spatially aware cell–cell interaction analysis, we link localized ligand signals to cell fate decisions. We also define biologically meaningful cellular neighborhoods based on aggregated extracellular cues, providing a blueprint to understand the coordination of human development at scale.