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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Nat+Commun
2015 ; 6
(ä): 8715
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Modelling kidney disease with CRISPR-mutant kidney organoids derived from human
pluripotent epiblast spheroids
#MMPMID26493500
Freedman BS
; Brooks CR
; Lam AQ
; Fu H
; Morizane R
; Agrawal V
; Saad AF
; Li MK
; Hughes MR
; Werff RV
; Peters DT
; Lu J
; Baccei A
; Siedlecki AM
; Valerius MT
; Musunuru K
; McNagny KM
; Steinman TI
; Zhou J
; Lerou PH
; Bonventre JV
Nat Commun
2015[Oct]; 6
(ä): 8715
PMID26493500
show ga
Human-pluripotent-stem-cell-derived kidney cells (hPSC-KCs) have important
potential for disease modelling and regeneration. Whether the hPSC-KCs can
reconstitute tissue-specific phenotypes is currently unknown. Here we show that
hPSC-KCs self-organize into kidney organoids that functionally recapitulate
tissue-specific epithelial physiology, including disease phenotypes after genome
editing. In three-dimensional cultures, epiblast-stage hPSCs form spheroids
surrounding hollow, amniotic-like cavities. GSK3? inhibition differentiates
spheroids into segmented, nephron-like kidney organoids containing cell
populations with characteristics of proximal tubules, podocytes and endothelium.
Tubules accumulate dextran and methotrexate transport cargoes, and express kidney
injury molecule-1 after nephrotoxic chemical injury. CRISPR/Cas9 knockout of
podocalyxin causes junctional organization defects in podocyte-like cells.
Knockout of the polycystic kidney disease genes PKD1 or PKD2 induces cyst
formation from kidney tubules. All of these functional phenotypes are distinct
from effects in epiblast spheroids, indicating that they are tissue specific. Our
findings establish a reproducible, versatile three-dimensional framework for
human epithelial disease modelling and regenerative medicine applications.
|Cell Differentiation
[MESH]
|Clustered Regularly Interspaced Short Palindromic Repeats
[MESH]