A comprehensive analysis of gene expression changes in a high replicate and open-source dataset of differentiating hiPSC-derived cardiomyocytes
Abstract We performed a comprehensive analysis of the transcriptional changes occurring during human induced pluripotent stem cell (hiPSC) differentiation to cardiomyocytes. Using single cell RNA-seq, we sequenced > 20,000 single cells from 55 independent samples representing two differentiation...
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Nature Portfolio
2021
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oai:doaj.org-article:d4fb933e376547c486f87bcf5fd173392021-12-02T16:35:19ZA comprehensive analysis of gene expression changes in a high replicate and open-source dataset of differentiating hiPSC-derived cardiomyocytes10.1038/s41598-021-94732-12045-2322https://doaj.org/article/d4fb933e376547c486f87bcf5fd173392021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94732-1https://doaj.org/toc/2045-2322Abstract We performed a comprehensive analysis of the transcriptional changes occurring during human induced pluripotent stem cell (hiPSC) differentiation to cardiomyocytes. Using single cell RNA-seq, we sequenced > 20,000 single cells from 55 independent samples representing two differentiation protocols and multiple hiPSC lines. Samples included experimental replicates ranging from undifferentiated hiPSCs to mixed populations of cells at D90 post-differentiation. Differentiated cell populations clustered by time point, with differential expression analysis revealing markers of cardiomyocyte differentiation and maturation changing from D12 to D90. We next performed a complementary cluster-independent sparse regression analysis to identify and rank genes that best assigned cells to differentiation time points. The two highest ranked genes between D12 and D24 (MYH7 and MYH6) resulted in an accuracy of 0.84, and the three highest ranked genes between D24 and D90 (A2M, H19, IGF2) resulted in an accuracy of 0.94, revealing that low dimensional gene features can identify differentiation or maturation stages in differentiating cardiomyocytes. Expression levels of select genes were validated using RNA FISH. Finally, we interrogated differences in cardiac gene expression resulting from two differentiation protocols, experimental replicates, and three hiPSC lines in the WTC-11 background to identify sources of variation across these experimental variables.Tanya GrancharovaKaytlyn A. GerbinAlexander B. RosenbergCharles M. RocoJoy E. ArakakiColette M. DeLizoStephanie Q. DinhRory M. Donovan-MaiyeMatthew HiranoAngelique M. NelsonJoyce TangJulie A. TheriotCalysta YanVilas MenonSean P. PalecekGeorg SeeligRuwanthi N. GunawardaneNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-21 (2021) |
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DOAJ |
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Medicine R Science Q |
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Medicine R Science Q Tanya Grancharova Kaytlyn A. Gerbin Alexander B. Rosenberg Charles M. Roco Joy E. Arakaki Colette M. DeLizo Stephanie Q. Dinh Rory M. Donovan-Maiye Matthew Hirano Angelique M. Nelson Joyce Tang Julie A. Theriot Calysta Yan Vilas Menon Sean P. Palecek Georg Seelig Ruwanthi N. Gunawardane A comprehensive analysis of gene expression changes in a high replicate and open-source dataset of differentiating hiPSC-derived cardiomyocytes |
| description |
Abstract We performed a comprehensive analysis of the transcriptional changes occurring during human induced pluripotent stem cell (hiPSC) differentiation to cardiomyocytes. Using single cell RNA-seq, we sequenced > 20,000 single cells from 55 independent samples representing two differentiation protocols and multiple hiPSC lines. Samples included experimental replicates ranging from undifferentiated hiPSCs to mixed populations of cells at D90 post-differentiation. Differentiated cell populations clustered by time point, with differential expression analysis revealing markers of cardiomyocyte differentiation and maturation changing from D12 to D90. We next performed a complementary cluster-independent sparse regression analysis to identify and rank genes that best assigned cells to differentiation time points. The two highest ranked genes between D12 and D24 (MYH7 and MYH6) resulted in an accuracy of 0.84, and the three highest ranked genes between D24 and D90 (A2M, H19, IGF2) resulted in an accuracy of 0.94, revealing that low dimensional gene features can identify differentiation or maturation stages in differentiating cardiomyocytes. Expression levels of select genes were validated using RNA FISH. Finally, we interrogated differences in cardiac gene expression resulting from two differentiation protocols, experimental replicates, and three hiPSC lines in the WTC-11 background to identify sources of variation across these experimental variables. |
| format |
article |
| author |
Tanya Grancharova Kaytlyn A. Gerbin Alexander B. Rosenberg Charles M. Roco Joy E. Arakaki Colette M. DeLizo Stephanie Q. Dinh Rory M. Donovan-Maiye Matthew Hirano Angelique M. Nelson Joyce Tang Julie A. Theriot Calysta Yan Vilas Menon Sean P. Palecek Georg Seelig Ruwanthi N. Gunawardane |
| author_facet |
Tanya Grancharova Kaytlyn A. Gerbin Alexander B. Rosenberg Charles M. Roco Joy E. Arakaki Colette M. DeLizo Stephanie Q. Dinh Rory M. Donovan-Maiye Matthew Hirano Angelique M. Nelson Joyce Tang Julie A. Theriot Calysta Yan Vilas Menon Sean P. Palecek Georg Seelig Ruwanthi N. Gunawardane |
| author_sort |
Tanya Grancharova |
| title |
A comprehensive analysis of gene expression changes in a high replicate and open-source dataset of differentiating hiPSC-derived cardiomyocytes |
| title_short |
A comprehensive analysis of gene expression changes in a high replicate and open-source dataset of differentiating hiPSC-derived cardiomyocytes |
| title_full |
A comprehensive analysis of gene expression changes in a high replicate and open-source dataset of differentiating hiPSC-derived cardiomyocytes |
| title_fullStr |
A comprehensive analysis of gene expression changes in a high replicate and open-source dataset of differentiating hiPSC-derived cardiomyocytes |
| title_full_unstemmed |
A comprehensive analysis of gene expression changes in a high replicate and open-source dataset of differentiating hiPSC-derived cardiomyocytes |
| title_sort |
comprehensive analysis of gene expression changes in a high replicate and open-source dataset of differentiating hipsc-derived cardiomyocytes |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/d4fb933e376547c486f87bcf5fd17339 |
| work_keys_str_mv |
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| _version_ |
1718383721357246464 |