Monocytic THP-1 cells diverge significantly from their primary counterparts: a comparative examination of the chromosomal conformations and transcriptomes

Abstract Immortalized cell lines have long been used as model systems to systematically investigate biological processes under controlled and reproducible conditions, providing insights that have greatly advanced cellular biology and medical sciences. Recently, the widely used monocytic leukemia cel...

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Autores principales:	Yulong Liu, Hua Li, Daniel M. Czajkowsky, Zhifeng Shao
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Hi-C Chromatin conformation Monocytes Macrophages Transcriptome Genetics QH426-470
Acceso en línea:	https://doaj.org/article/3656e5d6437145faa8778eee9c0072a6
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spelling	oai:doaj.org-article:3656e5d6437145faa8778eee9c0072a62021-11-07T12:15:23ZMonocytic THP-1 cells diverge significantly from their primary counterparts: a comparative examination of the chromosomal conformations and transcriptomes10.1186/s41065-021-00205-w1601-5223https://doaj.org/article/3656e5d6437145faa8778eee9c0072a62021-11-01T00:00:00Zhttps://doi.org/10.1186/s41065-021-00205-whttps://doaj.org/toc/1601-5223Abstract Immortalized cell lines have long been used as model systems to systematically investigate biological processes under controlled and reproducible conditions, providing insights that have greatly advanced cellular biology and medical sciences. Recently, the widely used monocytic leukemia cell line, THP-1, was comprehensively examined to understand mechanistic relationships between the 3D chromatin structure and transcription during the trans-differentiation of monocytes to macrophages. To corroborate these observations in primary cells, we analyze in situ Hi-C and RNA-seq data of human primary monocytes and their differentiated macrophages in comparison to that obtained from the monocytic/macrophagic THP-1 cells. Surprisingly, we find significant differences between the primary cells and the THP-1 cells at all levels of chromatin structure, from loops to topologically associated domains to compartments. Importantly, the compartment-level differences correlate significantly with transcription: those genes that are in A-compartments in the primary cells but are in B-compartments in the THP-1 cells exhibit a higher level of expression in the primary cells than in the THP-1 cells, and vice versa. Overall, the genes in these different compartments are enriched for a wide range of pathways, and, at least in the case of the monocytic cells, their altered expression in certain pathways in the THP-1 cells argues for a less immune cell-like phenotype, suggesting that immortalization or prolonged culturing of THP-1 caused a divergence of these cells from their primary counterparts. It is thus essential to reexamine phenotypic details observed in cell lines with their primary counterparts so as to ensure a proper understanding of functional cell states in vivo.Yulong LiuHua LiDaniel M. CzajkowskyZhifeng ShaoBMCarticleHi-CChromatin conformationMonocytesMacrophagesTranscriptomeGeneticsQH426-470ENHereditas, Vol 158, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hi-C Chromatin conformation Monocytes Macrophages Transcriptome Genetics QH426-470
spellingShingle	Hi-C Chromatin conformation Monocytes Macrophages Transcriptome Genetics QH426-470 Yulong Liu Hua Li Daniel M. Czajkowsky Zhifeng Shao Monocytic THP-1 cells diverge significantly from their primary counterparts: a comparative examination of the chromosomal conformations and transcriptomes
description	Abstract Immortalized cell lines have long been used as model systems to systematically investigate biological processes under controlled and reproducible conditions, providing insights that have greatly advanced cellular biology and medical sciences. Recently, the widely used monocytic leukemia cell line, THP-1, was comprehensively examined to understand mechanistic relationships between the 3D chromatin structure and transcription during the trans-differentiation of monocytes to macrophages. To corroborate these observations in primary cells, we analyze in situ Hi-C and RNA-seq data of human primary monocytes and their differentiated macrophages in comparison to that obtained from the monocytic/macrophagic THP-1 cells. Surprisingly, we find significant differences between the primary cells and the THP-1 cells at all levels of chromatin structure, from loops to topologically associated domains to compartments. Importantly, the compartment-level differences correlate significantly with transcription: those genes that are in A-compartments in the primary cells but are in B-compartments in the THP-1 cells exhibit a higher level of expression in the primary cells than in the THP-1 cells, and vice versa. Overall, the genes in these different compartments are enriched for a wide range of pathways, and, at least in the case of the monocytic cells, their altered expression in certain pathways in the THP-1 cells argues for a less immune cell-like phenotype, suggesting that immortalization or prolonged culturing of THP-1 caused a divergence of these cells from their primary counterparts. It is thus essential to reexamine phenotypic details observed in cell lines with their primary counterparts so as to ensure a proper understanding of functional cell states in vivo.
format	article
author	Yulong Liu Hua Li Daniel M. Czajkowsky Zhifeng Shao
author_facet	Yulong Liu Hua Li Daniel M. Czajkowsky Zhifeng Shao
author_sort	Yulong Liu
title	Monocytic THP-1 cells diverge significantly from their primary counterparts: a comparative examination of the chromosomal conformations and transcriptomes
title_short	Monocytic THP-1 cells diverge significantly from their primary counterparts: a comparative examination of the chromosomal conformations and transcriptomes
title_full	Monocytic THP-1 cells diverge significantly from their primary counterparts: a comparative examination of the chromosomal conformations and transcriptomes
title_fullStr	Monocytic THP-1 cells diverge significantly from their primary counterparts: a comparative examination of the chromosomal conformations and transcriptomes
title_full_unstemmed	Monocytic THP-1 cells diverge significantly from their primary counterparts: a comparative examination of the chromosomal conformations and transcriptomes
title_sort	monocytic thp-1 cells diverge significantly from their primary counterparts: a comparative examination of the chromosomal conformations and transcriptomes
publisher	BMC
publishDate	2021
url	https://doaj.org/article/3656e5d6437145faa8778eee9c0072a6
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Monocytic THP-1 cells diverge significantly from their primary counterparts: a comparative examination of the chromosomal conformations and transcriptomes

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