Single-cell spatial mapping of human kidney development implicates the microenvironment in guiding cell fate decisions
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.
Authors
- Laura S. Finn (ORCID: https://orcid.org/0000-0002-7931-7873)
- Samuel Grindel (ORCID: https://orcid.org/0000-0001-8280-312X)
- Juan Pablo Arroyo (ORCID: https://orcid.org/0000-0002-5992-5011)
- Nancy R. Zhang (ORCID: https://orcid.org/0000-0002-0880-5749)
- Aria Huang (ORCID: https://orcid.org/0009-0009-3042-3171)
- Oren Pleniceanu
- Grace Rabinowitz (ORCID: https://orcid.org/0000-0002-0494-280X)
- Joo‐Seop Park (ORCID: https://orcid.org/0000-0002-4190-4386)
- Boaz Weisz (ORCID: https://orcid.org/0000-0003-1606-452X)
- Paola Romagnani (ORCID: https://orcid.org/0000-0002-1774-8088)
- Rena Levin-Klein (ORCID: https://orcid.org/0000-0001-7067-2185)
- Carolina Conte (ORCID: https://orcid.org/0000-0002-7679-2935)
- Konstantin A. Klötzer (ORCID: https://orcid.org/0009-0005-5022-2706)
- Amin Abedini (ORCID: https://orcid.org/0000-0002-8875-0070)
- Katalin Suszták (ORCID: https://orcid.org/0000-0002-1005-3726)
- Pazit Beckerman (ORCID: https://orcid.org/0000-0003-3061-6757)
- Kotaro Sasaki (ORCID: https://orcid.org/0000-0002-5604-2651)
- Bernhard Dumoulin (ORCID: https://orcid.org/0000-0003-4728-4250)
- Alex J. Hughes (ORCID: https://orcid.org/0000-0001-6801-3455)
- Andi Bergeson (ORCID: https://orcid.org/0009-0008-8128-6974)
- Mingyao Li (ORCID: https://orcid.org/0000-0001-8180-0621)
- Eunji Ha (ORCID: https://orcid.org/0000-0001-8618-8347)
- Jonathan Levinsohn
- Paul Titchenell
Institutions
- Northwestern University (US)
- Children's Hospital of Philadelphia (US)
- Tel Aviv University (IL)
- California Institute for Regenerative Medicine (US)
- Sheba Medical Center (IL)
- Meyer Children's Hospital (IT)
- Penn Center for AIDS Research (US)
- Hypertension Institute (US)
- University of Florence (IT)
- University of Pennsylvania (US)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Nature Genetics
- Published
- 2026-07-30
- DOI
- https://doi.org/10.1038/s41588-026-02665-0
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.00