Organ Regeneration Based on Developmental Biology

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Oct3/4

ES/iPS

T

Nascent

Mesoderm

T

Hox1 1

Posterior

Nascent

Mesoderm

Osr1

Wt 1

Hox11

Posterior

Intermediate

Mesoderm

Osr1

Wt 1

Hox11

Pax2

Six2

Metanephric

Mesenchyme

ActivinBmp/high Wnt Bmp/high Wnt Activin/Bmmid Wnt/RAp

RA Activin

Bmp/RA

Fgf9/low Wnt

lineage

posteriorization specification maturation

Nascent

Mesoderm

induction

d e

b c

a

Fig. 9.7 In vitro reconstitution of three-dimensional kidney structures. (a) Model of directed dif-
ferentiation of pluripotent stem cells toward the metanephric mesenchyme. (b–e) Development of
three-dimensional kidney structures from mouse ES cells and human iPS cells. Immunostaining of
induced nephron progenitors for the nephric tubule marker E-cadherin (green) and the glomerular
markers nephrin (yellow) and Wt1 (red). (b, c) Lower magnification images of induced mouse (b)
and human (c) kidney tissue. (d, e) Higher magnification images of induced mouse (d) and human
(e) kidney tissue. Scale bars, 50 μm (b, c), 20 μm (d, e). ES cells, embryonic stem cells; iPS cells,
induced pluripotent stem cells; RA retinoic acid

A. Taguchi and R. Nishinakamura