Soluble signals released by neighboring cells direct how the human kidney is built
Penn Medicine researchers have built the first spatial map of the developing human kidney, showing that soluble signals from neighboring cells steer what each cell becomes.
2 min. read
A human kidney is built once, before birth, and the rules guiding its construction have been largely inferred from animal models. Researchers have now read those rules directly in human tissue. Experts at Penn Medicine have found that developing cells are steered by soluble signals released by their neighbors—and identified the insulin-like growth factor 2 (IGF2) as a key signal that sustains the kidney’s stem-like cells. The study is published in Nature Genetics and conducted by the Penn-CHOP Kidney Innovation Center, a research collaboration between the Perelman School of Medicine and Children’s Hospital of Philadelphia, working with bioengineers from Penn’s School of Engineering and Applied Science and the Institute for Regenerative Medicine.
To capture development as it occurs in intact tissue, the team combined single-cell RNA sequencing with two spatial transcriptomics platforms, analyzing more than 700,000 cells from human fetal kidneys between 12.5 and 20.5 weeks of gestation. Conventional single-cell sequencing requires dissolving tissue into separate cells, which discards exactly what development depends on: where each cell sits and which signals reach it. The spatial approach preserves that context, letting the researchers place every cell, and every stage of its differentiation, back onto the map of the developing organ.
“A kidney is not built by cells working alone,” says Katalin Susztak, the Willard and Rhoda Ware Professor of Diabetes and Metabolic Diseases IV and co-director of the Penn-CHOP Kidney Innovation Center, who co-led the study. “Every cell has to know where it is, what its neighbors are releasing, and what it is supposed to become—and it has to get this right roughly a million times over. We could already see which cells were present. What we could not see were the signals passing between them.”
Because the researchers could follow differentiation across physical space rather than in the abstract, they were able to pinpoint the anatomical locations where developing cells commit to one path or another, and to revise the accepted sequence of those decisions in the human kidney.
“The kidney is a physical structure, and physical context is not incidental to how it forms—it is instructive,” says Alex J. Hughes of the School of Engineering and Applied Science and the Institute for Regenerative Medicine, who co-led the study with Susztak. “Being able to read the signaling environment a cell actually experiences, rather than inferring it from the cell types nearby, changes what we can build.”
When the Schuylkill swallowed the city: Lessons from Hurricane Ida’s historic flood
New Penn research shows that Hurricane Ida wasn’t a once-in-a-century anomaly but a preview of how climate change, urbanization, and aging infrastructure are rewriting flood risk.
The Fed explained: What it does and why it matters
Former Philadelphia Fed President Patrick Harker and financial historian Peter Conti-Brown, both Wharton professors, unpack the central bank’s origins, its unusual structure, and the quiet ways it shapes the economy
How population changes are impacting primary education worldwide
Research from Penn sociologist Emily Hannum and colleagues reveals regional trends in whether school-age populations are increasing, plateauing, or decreasing—and shows how different countries are responding.
A bioengineered bean gum from the lab of Penn Dental’s Henry Daniell is found to reduce the levels of three microbes associated with head and neck squamous cell cancer to almost zero, without affecting the beneficial bacteria normally found in the mouth.
Fighting oral cancer with bioengineered chewing gum
Research led by Penn Dental’s Henry Daniell shows that antiviral and antibacterial chewing gums reduce the levels of three microbes linked to worse outcomes in oral cancers, paving the way for more effective and affordable therapies.
