期刊
STEM CELL RESEARCH
卷 17, 期 1, 页码 130-139出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.scr.2016.06.001
关键词
Induced pluripotent stem cells; Differentiation; Nephron progenitors; Podocytes
资金
- European Research Council under the European Community's Seventh Framework Programme (FP7)/ERC Grant [268632]
- Innovative Medicines Initiative Joint Undertaking [115439]
- European Community
- EFPIA companies
- Roche Postdoctoral Fellowship Program [A1412744-A17]
- European Research Council (ERC) [268632] Funding Source: European Research Council (ERC)
Generating human podocytes in vitro could offer a unique opportunity to study human diseases. Here, we describe a simple and efficient protocol for obtaining functional podocytes in vitro from human induced pluripotent stem cells. Cells were exposed to a three-step protocol, which induced their differentiation into intermediate mesoderm, then into nephron progenitors and, finally, into mature podocytes. After differentiation, cells expressed the main podocyte markers, such as synaptopodin, WT1, alpha-Actinin-4, P-cadherin and nephrin at the protein and mRNA level, and showed the low proliferation rate typical of mature podocytes. Exposure to Angiotensin II significantly decreased the expression of podocyte genes and cells underwent cytoskeleton rearrangement. Cells were able to internalize albumin and self-assembled into chimeric 3D structures in combination with dissociated embryonic mouse kidney cells. Overall, these findings demonstrate the establishment of a robust protocol that, mimicking developmental stages, makes it possible to derive functional podocytes in vitro. (C) 2016 The Authors. Published by Elsevier B.V.
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