169(WT1, MAFB, FOXD1, TCF21, and VEGFA), typical slit diaphragm-related genes
(NPHS1, NPHS2, CD2AP, CLIC5, and dendrin), basolateral adhesion molecules
(claudin 5 and integrin α3), and causative genes for hereditary kidney diseases
(phospholipase ε1 and Myh9) (Table 9.1).
Specific interactions between vascular endothelial cells and podocytes are essen-
tial for normal glomerular development. Indeed, the induced glomerular podocytes
underwent further maturation following their transplantation to beneath the kidney
capsule of immunodeficient mice. Here, host mouse vasculature integrated with the
glomeruli of the transplanted tissue and the foot process and slit diaphragms that
developed were more distinct than those formed in vitro. These findings indicate
that human iPSC-derived glomerular podocytes matured further following trans-
plantation, possibly under the influence of host vascular endothelial cells and circu-
lation (Fig. 9.10).
COLWT1PODXLa
b
c
NephrinNephrinNephrinMergedMergedMergedMergedMergedMergedFig. 9.9 Induced podocytes exhibit apicobasal polarity and basal localization of nephrin. (a)
Nephrin (magenta) and WT1 (green) staining of the induced glomerulus at day 9. (b) Nephrin
(magenta) and type IV collagen (COL, green) staining. (c) Nephrin (magenta) and podocalyxin
(PODXL, green) staining. The left columns are at lower magnification to show a whole glomeru-
lus. The right two columns are singly stained, while the left two columns represent merged images.
Arrows: nephrin proteins localized to the basal domain; arrowheads: nephrin-positive dot-like or
filamentous structures. Scale bars, 10 μm
9 Early Kidney Specification and Its Recapitulation by Pluripotent Stem Cells