In Vivo Developmental Trajectories of Human Podocyte Inform In Vitro Differentiation of Pluripotent Stem Cell-Derived Podocytes.
Dev Cell
; 50(1): 102-116.e6, 2019 07 01.
Article
em En
| MEDLINE
| ID: mdl-31265809
ABSTRACT
The renal corpuscle of the kidney comprises a glomerular vasculature embraced by podocytes and supported by mesangial myofibroblasts, which ensure plasma filtration at the podocyte-generated slit diaphragm. With a spectrum of podocyte-expressed gene mutations causing chronic disease, an enhanced understanding of podocyte development and function to create relevant in vitro podocyte models is a clinical imperative. To characterize podocyte development, scRNA-seq was performed on human fetal kidneys, identifying distinct transcriptional signatures accompanying the differentiation of functional podocytes from progenitors. Interestingly, organoid-generated podocytes exhibited highly similar, progressive transcriptional profiles despite an absence of the vasculature, although abnormal gene expression was pinpointed in late podocytes. On transplantation into mice, organoid-derived podocytes recruited the host vasculature and partially corrected transcriptional profiles. Thus, human podocyte development is mostly intrinsically regulated and vascular interactions refine maturation. These studies support the application of organoid-derived podocytes to model disease and to restore or replace normal kidney functions.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Organoides
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Diferenciação Celular
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Regulação da Expressão Gênica no Desenvolvimento
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Podócitos
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Células-Tronco Pluripotentes Induzidas
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Análise de Célula Única
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Glomérulos Renais
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article