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<p>Kidney organoids derived from human induced pluripotent stem cells lack a proper vasculature, hampering their applicability. Transplantation prevents the loss of organoid endothelial cells (ECs) observed in vitro, and promotes vascularization. In this study, we transplanted kidney organoids in chicken embryos and deployed single-cell RNA sequencing of ~12,000 organoid ECs to delineate their molecular landscape and identify key changes associated with transplantation. Transplantation significantly altered EC phenotypic composition. Consistent with angiogenesis, proliferating EC populations expanded 8 days after transplantation. Importantly, ECs underwent a major vein-to-arterial phenotypic shift. One of the transplantation-specific arterial EC populations, characterized by laminar shear stress response and Notch signalling, showed a similar transcriptome as human fetal kidney arterial/afferent arteriolar ECs. Consistently, transplantation-induced transcriptional changes involved proangiogenic and arteriogenic SOX7 transcription factor upregulation and regulon enrichment. These findings point to blood flow and candidate transcription factors such as SOX7 as possible targets to enhance kidney organoid vascularization.</p>

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Single cell transcriptomics of human kidney organoid endothelium reveals vessel growth processes and arterial maturation upon transplantation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月1日

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  • Marije Koning,
  • Sébastien J. Dumas,
  • Elda Meta,
  • Ellen Lievers,
  • Annemarie M. A. de Graaf,
  • Mila Borri,
  • Lynn J. Nai Chung Tong,
  • Xue Liang,
  • Ping Liu,
  • Fang Chen,
  • Lin Lin,
  • Yonglun Luo,
  • Peter Carmeliet,
  • Cathelijne W. van den Berg,
  • Ton J. Rabelink

摘要

Kidney organoids derived from human induced pluripotent stem cells lack a proper vasculature, hampering their applicability. Transplantation prevents the loss of organoid endothelial cells (ECs) observed in vitro, and promotes vascularization. In this study, we transplanted kidney organoids in chicken embryos and deployed single-cell RNA sequencing of ~12,000 organoid ECs to delineate their molecular landscape and identify key changes associated with transplantation. Transplantation significantly altered EC phenotypic composition. Consistent with angiogenesis, proliferating EC populations expanded 8 days after transplantation. Importantly, ECs underwent a major vein-to-arterial phenotypic shift. One of the transplantation-specific arterial EC populations, characterized by laminar shear stress response and Notch signalling, showed a similar transcriptome as human fetal kidney arterial/afferent arteriolar ECs. Consistently, transplantation-induced transcriptional changes involved proangiogenic and arteriogenic SOX7 transcription factor upregulation and regulon enrichment. These findings point to blood flow and candidate transcription factors such as SOX7 as possible targets to enhance kidney organoid vascularization.