In utero gene expression in the Slc39a8(neo/neo) knockdown mouse.
Jing ChenMarina Gálvez-PeraltaXiang ZhangJingyuan DengZijuan LiuDaniel W NebertPublished in: Scientific reports (2018)
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.
Keyphrases
- wild type
- gene expression
- transcription factor
- rna seq
- hematopoietic stem cell
- single cell
- mouse model
- genome wide
- genome wide identification
- dna methylation
- ionic liquid
- type diabetes
- endothelial cells
- high fat diet induced
- physical activity
- bioinformatics analysis
- machine learning
- insulin resistance
- metabolic syndrome
- young adults
- risk assessment
- deep learning
- dna binding
- binding protein
- iron deficiency
- transition metal
- birth weight