In utero gene expression in the Slc39a8(neo/neo) knockdown mouse

Abstract Slc39a8 encodes ZIP8, a divalent cation/bicarbonate symporter expressed in pluripotent mouse embryonic stem cells, and therefore ubiquitous in adult tissues; ZIP8 influxes Zn2+, Mn2+ and Fe2+. Slc39a8(neo/neo) knockdown mice exhibit 10–15% of wild-type ZIP8 mRNA and protein levels, and show...

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Autores principales:	Jing Chen, Marina Gálvez-Peralta, Xiang Zhang, Jingyuan Deng, Zijuan Liu, Daniel W. Nebert
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/32e704fac5234eef94815e00e2b0392f
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spelling	oai:doaj.org-article:32e704fac5234eef94815e00e2b0392f2021-12-02T16:08:04ZIn utero gene expression in the Slc39a8(neo/neo) knockdown mouse10.1038/s41598-018-29109-y2045-2322https://doaj.org/article/32e704fac5234eef94815e00e2b0392f2018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29109-yhttps://doaj.org/toc/2045-2322Abstract Slc39a8 encodes ZIP8, a divalent cation/bicarbonate symporter expressed in pluripotent mouse embryonic stem cells, and therefore ubiquitous in adult tissues; ZIP8 influxes Zn2+, Mn2+ and Fe2+. Slc39a8(neo/neo) knockdown mice exhibit 10–15% of wild-type ZIP8 mRNA and protein levels, and show pleiotropic phenotype of stunted growth, neonatal lethality, multi-organ dysmorphogenesis, and dysregulated hematopoiesis manifested as severe anemia. Herein we performed RNA-seq analysis of gestational day (GD)13.5 yolk sac and placenta, and GD16.5 liver, kidney, lung, heart and cerebellum, comparing Slc39a8(neo/neo) with Slc39a8(+/+) wild-type. Meta-data analysis of differentially-expressed genes revealed 29 unique genes from all tissues — having enriched GO categories associated with hematopoiesis and hypoxia and KEGG categories of complement, response to infection, and coagulation cascade — consistent with dysregulated hematopoietic stem cell fate. Based on transcription factor (TF) profiles in the JASPAR database, and searching for TF-binding sites enriched by Pscan, we identified numerous genes encoding zinc-finger and other TFs associated with hematopoietic stem cell functions. We conclude that, in this mouse model, deficient ZIP8-mediated divalent cation transport affects zinc-finger (e.g. GATA proteins) and other TFs interacting with GATA proteins (e.g. TAL1), predominantly in yolk sac. These data strongly support the phenotype of dysmorphogenesis and anemia seen in Slc39a8(neo/neo) mice in utero.Jing ChenMarina Gálvez-PeraltaXiang ZhangJingyuan DengZijuan LiuDaniel W. NebertNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jing Chen Marina Gálvez-Peralta Xiang Zhang Jingyuan Deng Zijuan Liu Daniel W. Nebert In utero gene expression in the Slc39a8(neo/neo) knockdown mouse
description	Abstract Slc39a8 encodes ZIP8, a divalent cation/bicarbonate symporter expressed in pluripotent mouse embryonic stem cells, and therefore ubiquitous in adult tissues; ZIP8 influxes Zn2+, Mn2+ and Fe2+. Slc39a8(neo/neo) knockdown mice exhibit 10–15% of wild-type ZIP8 mRNA and protein levels, and show pleiotropic phenotype of stunted growth, neonatal lethality, multi-organ dysmorphogenesis, and dysregulated hematopoiesis manifested as severe anemia. Herein we performed RNA-seq analysis of gestational day (GD)13.5 yolk sac and placenta, and GD16.5 liver, kidney, lung, heart and cerebellum, comparing Slc39a8(neo/neo) with Slc39a8(+/+) wild-type. Meta-data analysis of differentially-expressed genes revealed 29 unique genes from all tissues — having enriched GO categories associated with hematopoiesis and hypoxia and KEGG categories of complement, response to infection, and coagulation cascade — consistent with dysregulated hematopoietic stem cell fate. Based on transcription factor (TF) profiles in the JASPAR database, and searching for TF-binding sites enriched by Pscan, we identified numerous genes encoding zinc-finger and other TFs associated with hematopoietic stem cell functions. We conclude that, in this mouse model, deficient ZIP8-mediated divalent cation transport affects zinc-finger (e.g. GATA proteins) and other TFs interacting with GATA proteins (e.g. TAL1), predominantly in yolk sac. These data strongly support the phenotype of dysmorphogenesis and anemia seen in Slc39a8(neo/neo) mice in utero.
format	article
author	Jing Chen Marina Gálvez-Peralta Xiang Zhang Jingyuan Deng Zijuan Liu Daniel W. Nebert
author_facet	Jing Chen Marina Gálvez-Peralta Xiang Zhang Jingyuan Deng Zijuan Liu Daniel W. Nebert
author_sort	Jing Chen
title	In utero gene expression in the Slc39a8(neo/neo) knockdown mouse
title_short	In utero gene expression in the Slc39a8(neo/neo) knockdown mouse
title_full	In utero gene expression in the Slc39a8(neo/neo) knockdown mouse
title_fullStr	In utero gene expression in the Slc39a8(neo/neo) knockdown mouse
title_full_unstemmed	In utero gene expression in the Slc39a8(neo/neo) knockdown mouse
title_sort	in utero gene expression in the slc39a8(neo/neo) knockdown mouse
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/32e704fac5234eef94815e00e2b0392f
work_keys_str_mv	AT jingchen inuterogeneexpressionintheslc39a8neoneoknockdownmouse AT marinagalvezperalta inuterogeneexpressionintheslc39a8neoneoknockdownmouse AT xiangzhang inuterogeneexpressionintheslc39a8neoneoknockdownmouse AT jingyuandeng inuterogeneexpressionintheslc39a8neoneoknockdownmouse AT zijuanliu inuterogeneexpressionintheslc39a8neoneoknockdownmouse AT danielwnebert inuterogeneexpressionintheslc39a8neoneoknockdownmouse
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In utero gene expression in the Slc39a8(neo/neo) knockdown mouse

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