Gene-Edited Human Kidney Organoids Reveal Mechanisms of Disease in Podocyte Development

Stem Cells

Volumn 35, Issue 12, 2017, Pages 2366-2378

  Kim, Yong Kyun ^a   Refaeli, Ido ^b   Brooks, Craig R ^c   Jing, Peifeng ^d   Gulieva, Ramila E ^a   Hughes, Michael R ^b   Cruz, Nelly M ^a   Liu, Yannan ^d   Churchill, Angela J ^a   Wang, Yuliang ^a,d   Fu, Hongxia ^a   Pippin, Jeffrey W ^a   Lin, Lih Y ^d   Shankland, Stuart J ^a   Vogl, A Wayne ^b   McNagny, Kelly M ^b   Freedman, Benjamin S ^a  

^a UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^c VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d University of Washington   (United States)

Author keywords

Adhesion receptors; Biophysics; Cell adhesion; Developmental biology; Differentiation; Focal segmental glomerulosclerosis; Foot processes; Gene targeting; Genome editing; Kidney; Nephrin; Nephrogenesis; Pluripotent stem cells; Podocalyxin; Podocin; Slit diaphragm

Indexed keywords

NEPHRIN; PODOCALYXIN; SYNAPTOPODIN; WT1 PROTEIN; SIALOGLYCOPROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; APICAL MEMBRANE; ARTICLE; BIOPHYSICS; CELL MATURATION; CELL MIGRATION; CELL ULTRASTRUCTURE; CONTROLLED STUDY; CRISPR-CAS9 SYSTEM; CYTOPLASM; DEVELOPMENTAL STAGE; FEMALE; GENE EDITING; GENE EXPRESSION; HUMAN; HUMAN CELL; MALE; MICROVILLUS; MOUSE; NONHUMAN; PHENOTYPE; PLURIPOTENT STEM CELL; PODOCYTE; TRANSCRIPTOMICS; ANIMAL; CELL ADHESION; CELL DIFFERENTIATION; CYTOLOGY; GENETICS; GLOMERULUS; KIDNEY; METABOLISM; ORGANOID; PATHOLOGY; PHYSIOLOGY;

ANIMALS; CELL ADHESION; CELL DIFFERENTIATION; GENE EDITING; HUMANS; KIDNEY; KIDNEY GLOMERULUS; MICE; ORGANOIDS; PLURIPOTENT STEM CELLS; PODOCYTES; SIALOGLYCOPROTEINS;

EID: 85037131294     PISSN: 10665099     EISSN: 15494918     Source Type: Journal    
DOI: 10.1002/stem.2707     Document Type: Article

References (44)

1. Barak H, Huh SH, Chen S et al. FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man. Dev Cell 2012;22:1191–1207.
2. Brown AC, Muthukrishnan SD, Oxburgh L. A synthetic niche for nephron progenitor cells. Dev Cell 2015;34:229–241.
3. Taguchi A, Kaku Y, Ohmori T et al. Redefining the in vivo origin of metanephric nephron progenitors enables generation of complex kidney structures from pluripotent stem cells. Cell Stem Cell 2014;14:53–67.
4. Takasato M, Er PX, Chiu HS et al. Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature 2015;526:564–568.
5. Freedman BS, Brooks CR, Lam AQ et al. Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids. Nat Commun 2015;6:8715.
6. Dekel B, Burakova T, Arditti FD et al. Human and porcine early kidney precursors as a new source for transplantation. Nat Med 2003;9:53–60.
7. Xinaris C, Benedetti V, Rizzo P et al. In vivo maturation of functional renal organoids formed from embryonic cell suspensions. J Am Soc Nephrol 2012;23:1857–1868.
8. Unbekandt M, Davies JA. Dissociation of embryonic kidneys followed by reaggregation allows the formation of renal tissues. Kidney Int 2010;77:407–416.
9. Rogers SA, Lowell JA, Hammerman NA et al. Transplantation of developing metanephroi into adult rats. Kidney Int 1998;54:27–37.
10. Thomson JA, Itskovitz-Eldor J, Shapiro SS et al. Embryonic stem cell lines derived from human blastocysts. Science 1998;282:1145–1147.
11. Takahashi K, Tanabe K, Ohnuki M et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131:861–872.
12. Lam AQ, Freedman BS, Morizane R et al. Rapid and efficient differentiation of human pluripotent stem cells into intermediate mesoderm that forms tubules expressing kidney proximal tubular markers. J Am Soc Nephrol 2014;25:1211–1225.
13. Morizane R, Lam AQ, Freedman BS et al. Nephron organoids derived from human pluripotent stem cells model kidney development and injury. Nat Biotechnol 2015;33:1193–1200.
14. Mae S, Shono A, Shiota F et al. Monitoring and robust induction of nephrogenic intermediate mesoderm from human pluripotent stem cells. Nat Commun 2013;4:1367.
15. Saleem MA, O'Hare MJ, Reiser J et al. A conditionally immortalized human podocyte cell line demonstrating nephrin and podocin expression. J Am Soc Nephrol 2002;13:630–638.
16. Kim YG, Alpers CE, Brugarolas J et al. The cyclin kinase inhibitor p21CIP1/WAF1 limits glomerular epithelial cell proliferation in experimental glomerulonephritis. Kidney Int 1999;55:2349–2361.
17. Ronconi E, Sagrinati C, Angelotti ML et al. Regeneration of glomerular podocytes by human renal progenitors. J Am Soc Nephrol 2009;20:322–332.
18. Reeves W, Caulfield JP, Farquhar MG. Differentiation of epithelial foot processes and filtration slits: Sequential appearance of occluding junctions, epithelial polyanion, and slit membranes in developing glomeruli. Lab Invest 1978;39:90–100.
19. Hartleben B, Schweizer H, Lubben P et al. Neph-Nephrin proteins bind the Par3-Par6-atypical protein kinase C (aPKC) complex to regulate podocyte cell polarity. J Biol Chem 2008;283:23033–23038.
20. Reiser J, Kriz W, Kretzler M et al. The glomerular slit diaphragm is a modified adherens junction. J Am Soc Nephrol 2000;11:1–8.
21. Doyonnas R, Kershaw DB, Duhme C et al. Anuria, omphalocele, and perinatal lethality in mice lacking the CD34-related protein podocalyxin. J Exp Med 2001;194:13–27.
22. Kestila M, Lenkkeri U, Mannikko M et al. Positionally cloned gene for a novel glomerular protein–nephrin–is mutated in congenital nephrotic syndrome. Mol Cell 1998;1:575–582.
23. Boute N, Gribouval O, Roselli S et al. NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nat Genet 2000;24:349–354.
24. Sharmin S, Taguchi A, Kaku Y et al. Human Induced Pluripotent Stem Cell-Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation. J Am Soc Nephrol 2016;27:1778–1791.
25. Debruin EJ, Hughes MR, Sina C et al. Podocalyxin regulates murine lung vascular permeability by altering endothelial cell adhesion. PLoS One 2014;9:e108881.
26. Jing P, Wu J, Liu GW et al. Photonic crystal optical tweezers with high efficiency for live biological samples and viability characterization. Sci Rep 2016;6:19924.
27. Anders S, Huber W. Differential expression analysis for sequence count data. Genome Biol 2010;11:R106.
28. Alexa A, Rahnenfuhrer J, Lengauer T. Improved scoring of functional groups from gene expression data by decorrelating GO graph structure. Bioinformatics 2006;22:1600–1607.
29. Kerjaschki D, Vernillo AT, Farquhar MG. Reduced sialylation of podocalyxin–the major sialoprotein of the rat kidney glomerulus–in aminonucleoside nephrosis. Am J Pathol 1985;118:343–349.
30. Ryan G, Steele-Perkins V, Morris JF et al. Repression of Pax-2 by WT1 during normal kidney development. Development 1995;121:867–875.
31. Bouchard M, Souabni A, Mandler M et al. Nephric lineage specification by Pax2 and Pax8. Genes Dev 2002;16:2958–2970.
32. Kann M, Ettou S, Jung YL et al. Genome-wide analysis of Wilms' tumor 1-controlled gene expression in podocytes reveals key regulatory mechanisms. J Am Soc Nephrol 2015;26:2097–2104.
33. Guo G, Morrison DJ, Licht JD et al. WT1 activates a glomerular-specific enhancer identified from the human nephrin gene. J Am Soc Nephrol 2004;15:2851–2856.
34. Horrillo A, Porras G, Ayuso MS et al. Loss of endothelial barrier integrity in mice with conditional ablation of podocalyxin (Podxl) in endothelial cells. Eur J Cell Biol 2016;95:265–276.
35. Chuang JZ, Chou SY, Sung CH. Chloride intracellular channel 4 is critical for the epithelial morphogenesis of RPE cells and retinal attachment. Mol Biol Cell 2010;21:3017–3028.
36. Wegner B, Al-Momany A, Kulak SC et al. CLIC5A, a component of the ezrin-podocalyxin complex in glomeruli, is a determinant of podocyte integrity. Am J Physiol Renal Physiol 2010;298:F1492–F1503.
37. Nielsen JS, Graves ML, Chelliah S et al. The CD34-related molecule podocalyxin is a potent inducer of microvillus formation. PLoS One 2007;2:e237.
38. Takeda T, Go WY, Orlando RA et al. Expression of podocalyxin inhibits cell-cell adhesion and modifies junctional properties in Madin-Darby canine kidney cells. Mol Biol Cell 2000;11:3219–3232.
39. Krieg M, Arboleda-Estudillo Y, Puech PH et al. Tensile forces govern germ-layer organization in zebrafish. Nat Cell Biol 2008;10:429–436.
40. Thie M, Rospel R, Dettmann W et al. Interactions between trophoblast and uterine epithelium: Monitoring of adhesive forces. Hum Reprod 1998;13:3211–3219.
41. Snyder KA, Hughes MR, Hedberg B et al. Podocalyxin enhances breast tumor growth and metastasis and is a target for monoclonal antibody therapy. Breast Cancer Res 2015;17:46.
42. Choo AB, Tan HL, Ang SN et al. Selection against undifferentiated human embryonic stem cells by a cytotoxic antibody recognizing podocalyxin-like protein-1. Stem Cells 2008;26:1454–1463.
43. Barua M, Shieh E, Schlondorff J et al. Exome sequencing and in vitro studies identified podocalyxin as a candidate gene for focal and segmental glomerulosclerosis. Kidney Int 2014;85:124–133.
44. St John PL, Abrahamson DR. Glomerular endothelial cells and podocytes jointly synthesize laminin-1 and -11 chains. Kidney Int 2001;60:1037–1046.