TY - JOUR
T1 - Identification of Predictive Markers for the Generation of Well-Differentiated Human Induced Pluripotent Stem Cell-Derived Kidney Organoids
AU - Du, Zhaoyu
AU - Shankar, Anusha S.
AU - Van Den Bosch, Thierry P.P.
AU - Korevaar, Sander S.
AU - Clahsen-Van Groningen, Marian
AU - Hoorn, Ewout J.
AU - Gribnau, Joost
AU - Reinders, Marlies E.J.
AU - Baan, Carla C.
AU - Hoogduijn, Martin J.
N1 - Funding Information:
The authors thank China Scholarship Council for their financial support on researcher and the colleagues at Pathology Department, Erasmus MC, for their support on sample processing.
Publisher Copyright:
© Copyright 2021, Mary Ann Liebert, Inc., publishers 2021.
PY - 2021/11/11
Y1 - 2021/11/11
N2 - Human-induced pluripotent stem cell (iPSC)-derived kidney organoids have the potential to advance studies to kidney development and disease. However, reproducible generation of kidney organoids is a challenge. A large variability in the percentage of nephron structures and the expression of kidney-specific genes was observed among organoids, showing no association with iPSC lines. To associate the quality of kidney organoid differentiation with predictive markers, a ranking system was developed based on the ratio of nephron structure determined by histological examination. Well-differentiated organoids were defined as organoids with >30% nephron structure and vice versa. Subsequently, correlations were made with expression profiles of iPSC markers, early kidney development markers, and fibrosis markers. Higher expression of sex-determining region Y-box 2 (SOX2) during differentiation was associated with poorly differentiated kidney organoid. Furthermore, early secretion of basic fibroblast growth factor (FGF2) predicted poorly differentiated kidney organoid. Of interest, whereas cadherin-1 (CDH1) expression in kidney organoids indicates distal tubules formation, onefold higher CDH1 expression in iPSC predicted poor differentiation. High expression of the stromal progenitor marker Forkhead Box D1 (FOXD1) and significantly increased TGFβ levels were found in well-differentiated kidney organoids. These early expression profiles could predict the outcome of kidney organoid formation. This study helps to improve the robustness of kidney organoid protocols.
AB - Human-induced pluripotent stem cell (iPSC)-derived kidney organoids have the potential to advance studies to kidney development and disease. However, reproducible generation of kidney organoids is a challenge. A large variability in the percentage of nephron structures and the expression of kidney-specific genes was observed among organoids, showing no association with iPSC lines. To associate the quality of kidney organoid differentiation with predictive markers, a ranking system was developed based on the ratio of nephron structure determined by histological examination. Well-differentiated organoids were defined as organoids with >30% nephron structure and vice versa. Subsequently, correlations were made with expression profiles of iPSC markers, early kidney development markers, and fibrosis markers. Higher expression of sex-determining region Y-box 2 (SOX2) during differentiation was associated with poorly differentiated kidney organoid. Furthermore, early secretion of basic fibroblast growth factor (FGF2) predicted poorly differentiated kidney organoid. Of interest, whereas cadherin-1 (CDH1) expression in kidney organoids indicates distal tubules formation, onefold higher CDH1 expression in iPSC predicted poor differentiation. High expression of the stromal progenitor marker Forkhead Box D1 (FOXD1) and significantly increased TGFβ levels were found in well-differentiated kidney organoids. These early expression profiles could predict the outcome of kidney organoid formation. This study helps to improve the robustness of kidney organoid protocols.
UR - http://www.scopus.com/inward/record.url?scp=85119303173&partnerID=8YFLogxK
U2 - 10.1089/scd.2021.0197
DO - 10.1089/scd.2021.0197
M3 - Article
C2 - 34549597
AN - SCOPUS:85119303173
SN - 1547-3287
VL - 30
SP - 1103
EP - 1114
JO - Stem Cells and Development
JF - Stem Cells and Development
IS - 22
ER -
