TY - JOUR

T1 - Feeder-free generation and transcriptome characterization of functional mesenchymal stromal cells from human pluripotent stem cells

AU - Luo, Lidan

AU - Zhou, Yan

AU - Zhang, Chenxi

AU - Huang, Jinrong

AU - Du, Jie

AU - Liao, Jinqi

AU - Bergholt, Natasja Leth

AU - Bünger, Cody

AU - Xu, Fengping

AU - Lin, Lin

AU - Tong, Guangdong

AU - Zhou, Guangqian

AU - Luo, Yonglun

PY - 2020

Y1 - 2020

N2 - Induced mesenchymal stromal cells (iMSCs) derived from human pluripotent stem cells (PSCs) are attractive cells for regenerative medicine. However, the transcriptome of iMSCs and signature genes that can distinguish MSCs from fibroblasts and other cell types are rarely explored. In this study, we reported an optimized feeder-free method for the generation of iMSCs from human pluripotent stem cells. These iMSCs display a typical MSC morphology, express classic MSC markers (CD29, CD44, CD73, CD90, CD105, CD166), are negative for lymphocyte markers (CD11b, CD14, CD31, CD34, CD45, HLA-DR), and are potent for osteogenic and chondrogenic differentiation. Using genome-wide transcriptome profiling, we created an easily accessible transcriptome reference for the process of differentiating PSCs into iMSCs. The iMSC transcriptome reference revealed clear patterns in the silencing of pluripotency genes, activation of lineage commitment genes, and activation of mesenchymal genes during iMSC generation. All previously known positive and negative markers for MSCs were confirmed by our iMSC transcriptomic reference, and most importantly, gene classification and time course analysis identified 52 genes including FN1, TGFB1, TAGLN and SERPINE1, which showed significantly higher expression in MSCs (over 3 folds) than fibroblasts and other cell types. Taken together, these results provide a useful method and important resources for developing and understanding iMSCs in regenerative medicine.

AB - Induced mesenchymal stromal cells (iMSCs) derived from human pluripotent stem cells (PSCs) are attractive cells for regenerative medicine. However, the transcriptome of iMSCs and signature genes that can distinguish MSCs from fibroblasts and other cell types are rarely explored. In this study, we reported an optimized feeder-free method for the generation of iMSCs from human pluripotent stem cells. These iMSCs display a typical MSC morphology, express classic MSC markers (CD29, CD44, CD73, CD90, CD105, CD166), are negative for lymphocyte markers (CD11b, CD14, CD31, CD34, CD45, HLA-DR), and are potent for osteogenic and chondrogenic differentiation. Using genome-wide transcriptome profiling, we created an easily accessible transcriptome reference for the process of differentiating PSCs into iMSCs. The iMSC transcriptome reference revealed clear patterns in the silencing of pluripotency genes, activation of lineage commitment genes, and activation of mesenchymal genes during iMSC generation. All previously known positive and negative markers for MSCs were confirmed by our iMSC transcriptomic reference, and most importantly, gene classification and time course analysis identified 52 genes including FN1, TGFB1, TAGLN and SERPINE1, which showed significantly higher expression in MSCs (over 3 folds) than fibroblasts and other cell types. Taken together, these results provide a useful method and important resources for developing and understanding iMSCs in regenerative medicine.

KW - Extracellular matrix

KW - Induced mesenchymal stromal cells (iMSCs)

KW - Marker

KW - Mesenchymal stromal cells

KW - Pluripotent stem cells

KW - Transcriptome

U2 - 10.1016/j.scr.2020.101990

DO - 10.1016/j.scr.2020.101990

M3 - Journal article

C2 - 32950887

AN - SCOPUS:85090986238

VL - 48

JO - Stem Cell Research

JF - Stem Cell Research

SN - 1873-5061

M1 - 101990

ER -