Transcriptomic entropy benchmarks stem cell-derived cardiomyocyte maturation against endogenous tissue at single cell level.

The immaturity of pluripotent stem cell (PSC)-derived tissues has emerged as a universal problem for their biomedical applications. While efforts have been made to generate adult-like cells from PSCs, direct benchmarking of PSC-derived tissues against in vivo development has not been established. Th...

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Autores principales:	Suraj Kannan, Michael Farid, Brian L Lin, Matthew Miyamoto, Chulan Kwon
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/837348608b634768ac6a20ed2cf424b7
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spelling	oai:doaj.org-article:837348608b634768ac6a20ed2cf424b72021-12-02T19:57:46ZTranscriptomic entropy benchmarks stem cell-derived cardiomyocyte maturation against endogenous tissue at single cell level.1553-734X1553-735810.1371/journal.pcbi.1009305https://doaj.org/article/837348608b634768ac6a20ed2cf424b72021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009305https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The immaturity of pluripotent stem cell (PSC)-derived tissues has emerged as a universal problem for their biomedical applications. While efforts have been made to generate adult-like cells from PSCs, direct benchmarking of PSC-derived tissues against in vivo development has not been established. Thus, maturation status is often assessed on an ad-hoc basis. Single cell RNA-sequencing (scRNA-seq) offers a promising solution, though cross-study comparison is limited by dataset-specific batch effects. Here, we developed a novel approach to quantify PSC-derived cardiomyocyte (CM) maturation through transcriptomic entropy. Transcriptomic entropy is robust across datasets regardless of differences in isolation protocols, library preparation, and other potential batch effects. With this new model, we analyzed over 45 scRNA-seq datasets and over 52,000 CMs, and established a cross-study, cross-species CM maturation reference. This reference enabled us to directly compare PSC-CMs with the in vivo developmental trajectory and thereby to quantify PSC-CM maturation status. We further found that our entropy-based approach can be used for other cell types, including pancreatic beta cells and hepatocytes. Our study presents a biologically relevant and interpretable metric for quantifying PSC-derived tissue maturation, and is extensible to numerous tissue engineering contexts.Suraj KannanMichael FaridBrian L LinMatthew MiyamotoChulan KwonPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 9, p e1009305 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Suraj Kannan Michael Farid Brian L Lin Matthew Miyamoto Chulan Kwon Transcriptomic entropy benchmarks stem cell-derived cardiomyocyte maturation against endogenous tissue at single cell level.
description	The immaturity of pluripotent stem cell (PSC)-derived tissues has emerged as a universal problem for their biomedical applications. While efforts have been made to generate adult-like cells from PSCs, direct benchmarking of PSC-derived tissues against in vivo development has not been established. Thus, maturation status is often assessed on an ad-hoc basis. Single cell RNA-sequencing (scRNA-seq) offers a promising solution, though cross-study comparison is limited by dataset-specific batch effects. Here, we developed a novel approach to quantify PSC-derived cardiomyocyte (CM) maturation through transcriptomic entropy. Transcriptomic entropy is robust across datasets regardless of differences in isolation protocols, library preparation, and other potential batch effects. With this new model, we analyzed over 45 scRNA-seq datasets and over 52,000 CMs, and established a cross-study, cross-species CM maturation reference. This reference enabled us to directly compare PSC-CMs with the in vivo developmental trajectory and thereby to quantify PSC-CM maturation status. We further found that our entropy-based approach can be used for other cell types, including pancreatic beta cells and hepatocytes. Our study presents a biologically relevant and interpretable metric for quantifying PSC-derived tissue maturation, and is extensible to numerous tissue engineering contexts.
format	article
author	Suraj Kannan Michael Farid Brian L Lin Matthew Miyamoto Chulan Kwon
author_facet	Suraj Kannan Michael Farid Brian L Lin Matthew Miyamoto Chulan Kwon
author_sort	Suraj Kannan
title	Transcriptomic entropy benchmarks stem cell-derived cardiomyocyte maturation against endogenous tissue at single cell level.
title_short	Transcriptomic entropy benchmarks stem cell-derived cardiomyocyte maturation against endogenous tissue at single cell level.
title_full	Transcriptomic entropy benchmarks stem cell-derived cardiomyocyte maturation against endogenous tissue at single cell level.
title_fullStr	Transcriptomic entropy benchmarks stem cell-derived cardiomyocyte maturation against endogenous tissue at single cell level.
title_full_unstemmed	Transcriptomic entropy benchmarks stem cell-derived cardiomyocyte maturation against endogenous tissue at single cell level.
title_sort	transcriptomic entropy benchmarks stem cell-derived cardiomyocyte maturation against endogenous tissue at single cell level.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/837348608b634768ac6a20ed2cf424b7
work_keys_str_mv	AT surajkannan transcriptomicentropybenchmarksstemcellderivedcardiomyocytematurationagainstendogenoustissueatsinglecelllevel AT michaelfarid transcriptomicentropybenchmarksstemcellderivedcardiomyocytematurationagainstendogenoustissueatsinglecelllevel AT brianllin transcriptomicentropybenchmarksstemcellderivedcardiomyocytematurationagainstendogenoustissueatsinglecelllevel AT matthewmiyamoto transcriptomicentropybenchmarksstemcellderivedcardiomyocytematurationagainstendogenoustissueatsinglecelllevel AT chulankwon transcriptomicentropybenchmarksstemcellderivedcardiomyocytematurationagainstendogenoustissueatsinglecelllevel
_version_	1718375787463180288

Transcriptomic entropy benchmarks stem cell-derived cardiomyocyte maturation against endogenous tissue at single cell level.

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