Unknown,Transcriptomics,Genomics,Proteomics

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Expression data from human iPS cells treated by a small molecule KY02111

ABSTRACT: Human pluripotent stem cells (hPSCs) such as embryonic stem cells and induced pluripotent stem cells are promising materials for cell-based regenerative therapies to heart diseases. However, until realization there are many hurdles such as high efficiency of cardiac differentiation of hPSCs and production of clinical-grade cardiac cells derived from hPSCs. Here, we show that a novel small molecule KY02111 robustly enhances differentiation to functional cardiomyocytes from hPSCs. To reveal how KY02111 function on promoting cardiac differentiation of hPSCs, we analyzed the gene expression profiles in KY02111-treated IMR90-1 hiPSCs using the microarray technique. At Day3 of cardiac differentiation from hiPSCs, KY02111 or DMSO was added in the culture and then the cell population was harvested after 12 or 24 hours for RNA extraction.

ORGANISM(S): Homo sapiens

SUBMITTER: Itsunari Minami

PROVIDER: E-GEOD-33622 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A small molecule that promotes cardiac differentiation of human pluripotent stem cells under defined, cytokine- and xeno-free conditions.

Minami Itsunari I Yamada Kohei K Otsuji Tomomi G TG Yamamoto Takuya T Shen Yan Y Otsuka Shinya S Kadota Shin S Morone Nobuhiro N Barve Maneesha M Asai Yasuyuki Y Tenkova-Heuser Tatyana T Heuser John E JE Uesugi Motonari M Aiba Kazuhiro K Nakatsuji Norio N

Cell reports 20121025 5

Human pluripotent stem cells (hPSCs), including embryonic stem cells and induced pluripotent stem cells, are potentially useful in regenerative therapies for heart disease. For medical applications, clinical-grade cardiac cells must be produced from hPSCs in a defined, cost-effective manner. Cell-based screening led to the discovery of KY02111, a small molecule that promotes differentiation of hPSCs to cardiomyocytes. Although the direct target of KY02111 remains unknown, results of the present ...[more]

PMID: 23103164

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Project description:We designed microRNA-responsive, modified mRNA switches (miR-switches) that quantitatively control their own translation level by determining the miRNA activities. We found that the three miR-switches (i.e., miR-1-, miR-208-, and miR-499-switches) enable to purify cardiomyocytes differentiated from hPSCs with high efficiency, accuracy, and safety. The purified cardiomyocytes were engrafted in mouse heart and did not form tumor. Simultaneous purification of two different cell types, cardiomyocytes and endothelial cells, was also performed by transfecting the mRNA responding to the both miR-208 and miR-126, into heterogeneous cell population derived from hPSCs. In addition, selective induction of apoptosis in noncardiomyocytes triggered by miR-1/208-Bim switch enriched cardiomyocytes without cell sorting. The mRNA switch could purify desired cell types and control cell death pathways by monitoring the miRNA expression dynamics during cell fate conversion. MYH6-EIP4 iPSCs for mRNA, N=3 MYH6-EIP4 day18 cardiomyocytes (before transfection) for mRNA, N=3 MYH6-EIP4 day19 cardiomyocytes (miR-1-switch day1) for mRNA, N=3 MYH6-EIP4 day19 cardiomyocytes (without transfection) for mRNA, N=3 MYH6-EIP4 day25 cardiomyocytes (miR-1-switch day7) for mRNA, N=3 MYH6-EIP4 day25 cardiomyocytes (without transfection) for mRNA, N=3 201B7 d22 miR-208a-BFP sorted cells for mRNA, N=1 201B7 d22 miR-208a-BFP negative fraction sorted cells for mRNA, N=1 201B7 d22 SIRPA+LIN- sorted cells for mRNA, N=1 201B7 d22 SIRPA+LIN- negative fraction sorted cells for mRNA, N=1 201B7 d22 VCAM1+ sorted cells for mRNA, N=1 201B7 d22 VCAM1+negative fraction sorted cells for mRNA, N=1 MYH6-EIP4 day19 cardiomyocytes (miR-208a-Bim-switch day1) for mRNA, N=1 MYH6-EIP4 day19 cardiomyocytes (without transfection) for mRNA, N=1 MYH6-EIP4 day21 cardiomyocytes (miR-208a-Bim-switch day7) for mRNA, N=1 MYH6-EIP4 day21 cardiomyocytes (without transfection) for mRNA, N=1 MYH6-EIP4 day25 cardiomyocytes (miR-208a-Bim-switch day7) for mRNA, N=1 MYH6-EIP4 day25 cardiomyocytes (without transfection) for mRNA, N=1

Dataset Information

Expression data from human iPS cells treated by a small molecule KY02111

Publications

A small molecule that promotes cardiac differentiation of human pluripotent stem cells under defined, cytokine- and xeno-free conditions.

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