Cellular Recruitment by Podocyte-Derived Pro-migratory Factors in Assembly of the Human Renal Filter
| Autor: | Matthew E. Thornton, Brendan H. Grubbs, Yan Wu, Andrew P. McMahon, Blue B. Lake, Jinjin Guo, Jill A. McMahon, Riana K. Parvez, Song Chen, Kun Zhang, Tracy S. Tran, Albert D. Kim |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cell type Kidney Disease 1.1 Normal biological development and functioning Renal and urogenital Omics Kidney development 02 engineering and technology Nephron Biology Article Podocyte 03 medical and health sciences Underpinning research medicine lcsh:Science Kidney Multidisciplinary Mesangial cell Cell Biology Biological Sciences 021001 nanoscience & nanotechnology Renal corpuscle 3. Good health Cell biology 030104 developmental biology medicine.anatomical_structure lcsh:Q 0210 nano-technology Developmental biology Developmental Biology |
| Zdroj: | iScience, Vol 20, Iss, Pp 402-414 (2019) iScience |
| ISSN: | 2589-0042 |
| Popis: | Summary Analysis of kidney disease-causing genes and pathology resulting from systemic diseases highlight the importance of the kidney's filtering system, the renal corpuscles. To elucidate the developmental processes that establish the renal corpuscle, we performed single-nucleus droplet-based sequencing of the human fetal kidney. This enabled the identification of nephron, interstitial, and vascular cell types that together generate the renal corpuscles. Trajectory analysis identified transient developmental gene expression, predicting precursors or mature podocytes express FBLN2, BMP4, or NTN4, in conjunction with recruitment, differentiation, and modeling of vascular and mesangial cell types into a functional filter. In vitro studies provide evidence that these factors exhibit angiogenic or mesangial recruiting and inductive properties consistent with a key organizing role for podocyte precursors in kidney development. Together these studies define a spatiotemporal developmental program for the primary filtration unit of the human kidney and provide novel insights into cell interactions regulating co-assembly of constituent cell types. Graphical Abstract Highlights • Single-nuclear RNA-seq analysis of human fetal kidney development • Co-ordinated programs of podocyte-driven glomerular development • Secreted podocyte factors act on endothelial and interstitial cells Biological Sciences; Cell Biology; Developmental Biology; Omics |
| Databáze: | OpenAIRE |
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