© Springer Nature Singapore Pte Ltd. 2017 153
T. Tsuji (ed.), Organ Regeneration Based on Developmental Biology,
DOI 10.1007/978-981-10-3768-9_9
Chapter 9
Early Kidney Specification and Its
Recapitulation by Pluripotent Stem Cells
Atsuhiro Taguchi and Ryuichi Nishinakamura
Abstract Successful generation of the kidney from pluripotent stem cells is chal-
lenging because of insufficient knowledge of the underlying developmental pro-
cesses. In addition to the technical difficulties of physically examining the early
stages of embryogenesis, the unique features surrounding the development of the
kidney from three distinct primordia hamper a more complete understanding of the
relevant cell fate acquisition mechanisms. We have recently addressed these issues
by combining in vivo lineage tracing experiments and ex vivo directed differentia-
tion culture systems. Our strategy has revealed the mechanism by which the kidney
morphogenic field is patterned along the anteroposterior axis and also identified the
key signals which promote posteriorization, specification, and maturation of neph-
ron progenitors from pluripotent stem cells. Importantly, these newly identified bio-
logical insights have enabled the production of three-dimensional complex nephron
structure from both mouse and human pluripotent stem cells, which would be a big
progress toward the realization of kidney regenerative medicine.
Keywords Kidney • Regeneration • Development • Stem cell • Nephron progenitor
- Wolffian duct • A-P patterning • Intermediate mesoderm
9.1 Introduction
The myriad types of cells that comprise a human develop from a single fertilized
egg. Recent advancements in developmental biology have identified multiple
growth factors responsible for cell-type specification during embryogenesis.
Furthermore, multiple cell types have been successfully differentiated from pluripo-
tent stem cells following the combination of these growth factors in vitro, demon-
strating the sufficiency of extrinsic cues for cell fate acquisition (Murry and Keller
2008 ). However, directing differentiation to defined cell types requires fine optimi-
zation of the factor exposure concentrations, timing, duration, and combinations.
A. Taguchi • R. Nishinakamura (*)
Department of Kidney Development, Institute of Molecular Embryology and Genetics,
Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan
e-mail: [email protected]; [email protected]