Microenvironment steers human kidney cell fate: insights from spatial single-cell mapping
A spatially resolved atlas combining single-cell RNA sequencing and spatial transcriptomics across fetal human kidneys (over 700k cells) shows that local microenvironments guide nephron cell fate, with an early but plastic decision between renal corpuscle and tubular lineages and evidence that some proximal-tubule–like cells can convert to PECs. The study links tissue location and signaling to fate decisions, identifying IGF2 as a locally acting cue promoting NPC renewal and early nephron differentiation, validated by mouse explant experiments and human organoid assays, and proposes a microenvironment-aware revision of nephrogenesis.