TY - JOUR
AU - Connor C. Fausto
AU - Fokion Glykofrydis
AU - Navneet Kumar
AU - Jack Schnell
AU - Reka L. Csipan
AU - Faith De Kuyper
AU - Minnal Kunnan
AU - Brendan Grubbs
AU - Matthew Thornton
AU - Michael Thompson
AU - Enmian Chang
AU - Xuduo Wen
AU - Manuel Pelayo
AU - MaryAnne Achieng
AU - Anoothi Seth
AU - Kelly Street
AU - Leonardo Morsut
AU - Nils O. Lindström
AB - Human stem cell–derived miniature organs, including kidney organoids, reproduce aspects of tissue development but lack reliable spatial patterning. In embryos, spatial organization is often established by developmental organizers that generate morphogenetic fields. However, how such organizing geometry operates in kidney nephrogenesis—and whether it can be reconstructed in vitro—has remained unclear. Using spatial transcriptomics of human kidney development, we found that nascent nephrons establish a collecting duct adjacent-to-distant polarity bordering a WNT11-WNT9B signaling boundary. Engineered WNT-secreting cellular organizers introduced into kidney organoids restored this organizing geometry, biasing distal nephron differentiation and orienting nephron morphogenesis toward the signal source, which demonstrates that developmental signaling geometry can be reconstructed synthetically to control tissue patterning.
BT - Science
DA - 2026-07-02
DO - 10.1126/science.adu9122
IS - 6806
N2 - Human stem cell–derived miniature organs, including kidney organoids, reproduce aspects of tissue development but lack reliable spatial patterning. In embryos, spatial organization is often established by developmental organizers that generate morphogenetic fields. However, how such organizing geometry operates in kidney nephrogenesis—and whether it can be reconstructed in vitro—has remained unclear. Using spatial transcriptomics of human kidney development, we found that nascent nephrons establish a collecting duct adjacent-to-distant polarity bordering a WNT11-WNT9B signaling boundary. Engineered WNT-secreting cellular organizers introduced into kidney organoids restored this organizing geometry, biasing distal nephron differentiation and orienting nephron morphogenesis toward the signal source, which demonstrates that developmental signaling geometry can be reconstructed synthetically to control tissue patterning.
PY - 2026
EP - eadu9122
T2 - Science
TI - Patterning human kidney organoids with synthetic Wnt-secreting organizers
UR - https://www.science.org/doi/10.1126/science.adu9122
VL - 393
Y2 - 2026-07-07
ER -