Dataset Information

RNA-seq analysis of Slc39a8(neo/neo) versus wild-type mice: yolk sac, placenta and fetal liver, kidney, lung, heart and cerebellum

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE111080 | GEO | 2018/07/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:The signaling cascades that direct the morphological differentiation of the vascular system during early embryogenesis are not well defined. To further understand the role of Notch signaling during endothelial differentiation, this study uses both an in vivo gain-of-function and in vivo loss-of-function approach. At embryonic day 9.5, embryos with activated Notch1 signaling in the endothelia display a variety of growth and cardiovascular defects, and die soon after E10.5. Most notably, the extra-embryonic vasculature of the yolk sac displays remodeling differentiation defects. In the wild-type yolk sac, the primary vascular network has begun to reorganize, forming the large primary vessels and the smaller capillaries. In the activated Notch1 embryos remodeling is defective; the vasculature have an enlarged surface with decreased inter-vessel space. Embryos with ablated Notch signaling also display growth and vascular defects at E9.5 similar to the activated Notch1 embryos, however they exhibit a lack of vascular remodeling in the yolk sac, retaining the simple vascular plexus seen at E8.5. These results indicate that Notch signaling plays a critical role in the remodeling of the vasculature in the early embryo, particularly in the extra embryonic region. A conditional transgenic system was used in this study to activate Notch signaling. The ubiquitous ROSA26Notch transgene with a Neo/stop cassette flanked by loxP sites, followed by the N1-ICD cDNA, was recombined with a Tie2-CRE mouse, resulting in the removal of the STOP cassette and the subsequent activation of the Notch1-intracellular domain. This allowed for the overexpression and expansion of Notch signaling in all endothelial cells. Male Tie2-Cre mice were mated with female ROSA26Notch mice and resulting embryos were dissected at embryonic day 9.5. To ablate Notch signaling, Tie2-Cre mice were used in a two generation cross to obtain Tie2-Cre; Rbpj flox/flox embryos. These embryos lack RBPJ binding activity in the endothelia. In both instances embryos were used for genotyping and the yolk sac were separated and used to isolate total RNA with an RNeasy mini kit. The RNA was analyzed with the Mouse Genome 430A Array from Affymetrix. Samples were performed in duplicate, and RNA from wild type yolk sac tissues was compared to activated Notch and RBPJ loss-of-function yolk sac tissues.

Dataset Information

RNA-seq analysis of Slc39a8(neo/neo) versus wild-type mice: yolk sac, placenta and fetal liver, kidney, lung, heart and cerebellum

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets