Evidence |
D29 organoids from all four iPSC lines contained cells representative of segments of a developing nephron (Fig.1c, d_nd Supplementary Fig.2).ascending limb (TAL;_LC12A1, Na-K-Cl cotransporter), and distal nephron cells (CDH1, E-cadherin;_QP2, aquaporin 2;_ATA3). There was no cluster enriched for_LC12A3(Na-Cl symporter; Supplementary Fig.2), a canonical marker of the distal convoluted tubule (DCT). The organoid single-cell profiles retained the proximal (podocyte) to distal axis of the Human nephron (Fig.1c, left) on visualization of the data using t-distributed stochastic nonlinear embedding (tSNE), unlike the discrete clusters seen in adult kidney (Fig.1c, right). We identified data-derived markers (Supplementary Table2), including osteopontin (SPP1)22_n the proximal tubular cell cluster, and_FDC223_nd_AL24_n the distal nephron cluster (Fig.1d_nd Supplementary Fig.3A), in line with scRNA-seq studies of Human adult and fetal kidney.D29 organoids also contained nephron progenitor cells (NPC) enriched in PAX2, LHX1 and PAX8 |