GSE111080
RNA-seq analysis of Slc39a8(neo/neo) versus wild-type mice: yolk sac, placenta and fetal liver, kidney, lung, heart and cerebellum
Slc39a8 encodes ZIP8, a ubiquitous divalent cation/bicarbonate symporter expressed in pluripotent mouse embryonic stem cell; ZIP8 influxes Zn2+, Mn2+ and Fe2+. Slc39a8(neo/neo) knockdown mice globally exhibit 10-15% of wild-type ZIP8 mRNA and protein levels, and show a pleiotropic phenotype of stunted growth, neonatal lethality, multi-organ dysmorphogenesis, and dysregulated hematopoiesis manifested as severe anemia. Herein we performed transcriptomics of GD13.5 yolk sac and placenta, and GD16.5 liver, kidney, lung, heart and cerebellum, comparing Slc39a8(neo/neo) with 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 the 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, numerous genes encoding zinc-finger TFs and associated with hematopoietic stem cell functions were identified. We conclude that, in this mouse model, deficient ZIP8-mediated Zn2+ transport affects zinc-finger (e.g. GATA proteins) and other transcription-factors (e.g. TAL1) predominantly in yolk sac, strongly supporting the observed dysmorphogenesis and anemia phenotype. Overall design: mRNA samples of Slc39a8(+/+) and Slc39a8(neo/neo) yolk sacs and placentas at GD13.5, fetal liver, kidney, lung, heart and cerebellum at GD16.5 were profiled in triplicate using Illumina HiSeq.