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Chromatin Interaction Changes during the iPSC-NPC Model to Facilitate the Study of Biologically Significant Genes Involved in Differentiation

Given the difficulties of obtaining diseased cells, differentiation of neurons from patient-specific human induced pluripotent stem cells (iPSCs) with neural progenitor cells (NPCs) as intermediate precursors is of great interest. While cellular and transcriptomic changes during the differentiation...

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Autores principales: Choi, Won-Young, Hwang, Ji-Hyun, Lee, Jin-Young, Cho, Ann-Na, Lee, Andrew J, Jung, Inkyung, Cho, Seung-Woo, Kim, Lark Kyun, Kim, Young-Joon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600115/
https://www.ncbi.nlm.nih.gov/pubmed/33050006
http://dx.doi.org/10.3390/genes11101176
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author Choi, Won-Young
Hwang, Ji-Hyun
Lee, Jin-Young
Cho, Ann-Na
Lee, Andrew J
Jung, Inkyung
Cho, Seung-Woo
Kim, Lark Kyun
Kim, Young-Joon
author_facet Choi, Won-Young
Hwang, Ji-Hyun
Lee, Jin-Young
Cho, Ann-Na
Lee, Andrew J
Jung, Inkyung
Cho, Seung-Woo
Kim, Lark Kyun
Kim, Young-Joon
author_sort Choi, Won-Young
collection PubMed
description Given the difficulties of obtaining diseased cells, differentiation of neurons from patient-specific human induced pluripotent stem cells (iPSCs) with neural progenitor cells (NPCs) as intermediate precursors is of great interest. While cellular and transcriptomic changes during the differentiation process have been tracked, little attention has been given to examining spatial re-organization, which has been revealed to control gene regulation in various cells. To address the regulatory mechanism by 3D chromatin structure during neuronal differentiation, we examined the changes that take place during differentiation process using two cell types that are highly valued in the study of neurodegenerative disease - iPSCs and NPCs. In our study, we used Hi-C, a derivative of chromosome conformation capture that enables unbiased, genome-wide analysis of interaction frequencies in chromatin. We showed that while topologically associated domains remained mostly the same during differentiation, the presence of differential interacting regions in both cell types suggested that spatial organization affects gene regulation of both pluripotency maintenance and neuroectodermal differentiation. Moreover, closer analysis of promoter–promoter pairs suggested that cell fate specification is under the control of cis-regulatory elements. Our results are thus a resourceful addition in benchmarking differentiation protocols and also provide a greater appreciation of NPCs, the common precursors from which required neurons for applications in neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, schizophrenia and spinal cord injuries are utilized.
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spelling pubmed-76001152020-11-01 Chromatin Interaction Changes during the iPSC-NPC Model to Facilitate the Study of Biologically Significant Genes Involved in Differentiation Choi, Won-Young Hwang, Ji-Hyun Lee, Jin-Young Cho, Ann-Na Lee, Andrew J Jung, Inkyung Cho, Seung-Woo Kim, Lark Kyun Kim, Young-Joon Genes (Basel) Article Given the difficulties of obtaining diseased cells, differentiation of neurons from patient-specific human induced pluripotent stem cells (iPSCs) with neural progenitor cells (NPCs) as intermediate precursors is of great interest. While cellular and transcriptomic changes during the differentiation process have been tracked, little attention has been given to examining spatial re-organization, which has been revealed to control gene regulation in various cells. To address the regulatory mechanism by 3D chromatin structure during neuronal differentiation, we examined the changes that take place during differentiation process using two cell types that are highly valued in the study of neurodegenerative disease - iPSCs and NPCs. In our study, we used Hi-C, a derivative of chromosome conformation capture that enables unbiased, genome-wide analysis of interaction frequencies in chromatin. We showed that while topologically associated domains remained mostly the same during differentiation, the presence of differential interacting regions in both cell types suggested that spatial organization affects gene regulation of both pluripotency maintenance and neuroectodermal differentiation. Moreover, closer analysis of promoter–promoter pairs suggested that cell fate specification is under the control of cis-regulatory elements. Our results are thus a resourceful addition in benchmarking differentiation protocols and also provide a greater appreciation of NPCs, the common precursors from which required neurons for applications in neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, schizophrenia and spinal cord injuries are utilized. MDPI 2020-10-08 /pmc/articles/PMC7600115/ /pubmed/33050006 http://dx.doi.org/10.3390/genes11101176 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Choi, Won-Young
Hwang, Ji-Hyun
Lee, Jin-Young
Cho, Ann-Na
Lee, Andrew J
Jung, Inkyung
Cho, Seung-Woo
Kim, Lark Kyun
Kim, Young-Joon
Chromatin Interaction Changes during the iPSC-NPC Model to Facilitate the Study of Biologically Significant Genes Involved in Differentiation
title Chromatin Interaction Changes during the iPSC-NPC Model to Facilitate the Study of Biologically Significant Genes Involved in Differentiation
title_full Chromatin Interaction Changes during the iPSC-NPC Model to Facilitate the Study of Biologically Significant Genes Involved in Differentiation
title_fullStr Chromatin Interaction Changes during the iPSC-NPC Model to Facilitate the Study of Biologically Significant Genes Involved in Differentiation
title_full_unstemmed Chromatin Interaction Changes during the iPSC-NPC Model to Facilitate the Study of Biologically Significant Genes Involved in Differentiation
title_short Chromatin Interaction Changes during the iPSC-NPC Model to Facilitate the Study of Biologically Significant Genes Involved in Differentiation
title_sort chromatin interaction changes during the ipsc-npc model to facilitate the study of biologically significant genes involved in differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600115/
https://www.ncbi.nlm.nih.gov/pubmed/33050006
http://dx.doi.org/10.3390/genes11101176
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