TY - JOUR
KW - Cell Line
KW - Drug Evaluation, Preclinical
KW - High-Throughput Screening Assays
KW - Humans
KW - induced pluripotent stem cells
KW - Proteomics
AU - Melpomeni Platani
AU - Hao Jiang
AU - Lindsay Davidson
AU - Santosh Hariharan
AU - Regis Doyonnas
AU - Angus I. Lamond
AU - Jason R. Swedlow
AB - We have developed a laboratory-based drug screening platform that uses a cohort of human induced pluripotent stem cell (hiPSC) lines, derived from different donors, to predict variable drug responses of potential clinical relevance. This builds on recent findings that pluripotent hiPSC lines express a broad repertoire of gene transcripts and proteins, whose expression levels reflect the genetic identity of the donor. We demonstrate that a cohort of hiPSC lines from different donors can be screened efficiently in their pluripotent state, using high-throughput Cell Painting assays. Variable phenotypic responses between hiPSC lines were detected with a wide range of clinically approved drugs, in use across multiple disease areas. Furthermore, information on mechanisms of drug-cell interactions underlying the observed variable responses was derived by using quantitative proteomic analysis to compare sets of hiPSC lines that had been stratified objectively, based upon variable response, Cell Painting data. We propose that information derived from comparative drug screening, using curated libraries of hiPSC lines from different donors, can help to improve the delivery of safe new drugs suitable for a broad range of genetic backgrounds and sexual diversity within human populations.
BT - PloS One
DA - 2025
DO - 10.1371/journal.pone.0323953
IS - 5
LA - eng
N2 - We have developed a laboratory-based drug screening platform that uses a cohort of human induced pluripotent stem cell (hiPSC) lines, derived from different donors, to predict variable drug responses of potential clinical relevance. This builds on recent findings that pluripotent hiPSC lines express a broad repertoire of gene transcripts and proteins, whose expression levels reflect the genetic identity of the donor. We demonstrate that a cohort of hiPSC lines from different donors can be screened efficiently in their pluripotent state, using high-throughput Cell Painting assays. Variable phenotypic responses between hiPSC lines were detected with a wide range of clinically approved drugs, in use across multiple disease areas. Furthermore, information on mechanisms of drug-cell interactions underlying the observed variable responses was derived by using quantitative proteomic analysis to compare sets of hiPSC lines that had been stratified objectively, based upon variable response, Cell Painting data. We propose that information derived from comparative drug screening, using curated libraries of hiPSC lines from different donors, can help to improve the delivery of safe new drugs suitable for a broad range of genetic backgrounds and sexual diversity within human populations.
PY - 2025
EP - e0323953
T2 - PloS One
TI - Screening for variable drug responses using human iPSC cohorts
VL - 20
SN - 1932-6203
ER -