PMID- 30013175
OWN - NLM
STAT- MEDLINE
DCOM- 20191028
LR  - 20191028
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Jul 16
TI  - In utero gene expression in the Slc39a8(neo/neo) knockdown mouse.
PG  - 10703
LID - 10.1038/s41598-018-29109-y [doi]
LID - 10703
AB  - Slc39a8 encodes ZIP8, a divalent cation/bicarbonate symporter expressed in 
      pluripotent mouse embryonic stem cells, and therefore ubiquitous in adult 
      tissues; ZIP8 influxes Zn(2+), Mn(2+) and Fe(2+). 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.
FAU - Chen, Jing
AU  - Chen J
AUID- ORCID: 0000-0002-6227-7393
AD  - Division of Biomedical Informatics, Cincinnati Children's Hospital Medical 
      Center, Cincinnati, Ohio, 45229, USA.
FAU - Galvez-Peralta, Marina
AU  - Galvez-Peralta M
AUID- ORCID: 0000-0001-7917-6559
AD  - Department of Environmental Health, University of Cincinnati College of Medicine, 
      Cincinnati, Ohio, 45267, USA.
AD  - Department of Pharmaceutical Sciences, West Virginia University Medical Center, 
      Morgantown, WV, 26506, USA.
FAU - Zhang, Xiang
AU  - Zhang X
AD  - Department of Environmental Health, University of Cincinnati College of Medicine, 
      Cincinnati, Ohio, 45267, USA.
FAU - Deng, Jingyuan
AU  - Deng J
AD  - Department of Environmental Health, University of Cincinnati College of Medicine, 
      Cincinnati, Ohio, 45267, USA.
AD  - Amazon.com, Inc., Seattle, WA, 98101, USA.
FAU - Liu, Zijuan
AU  - Liu Z
AD  - Department of Biological Sciences, Oakland University, Rochester, MI, 48309, USA.
FAU - Nebert, Daniel W
AU  - Nebert DW
AD  - Department of Environmental Health, University of Cincinnati College of Medicine, 
      Cincinnati, Ohio, 45267, USA. dan.nebert@uc.edu.
LA  - eng
GR  - P30 ES006096/ES/NIEHS NIH HHS/United States
GR  - R01 ES010416/ES/NIEHS NIH HHS/United States
GR  - T32 ES016646/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180716
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Cation Transport Proteins)
RN  - 0 (GATA Transcription Factors)
RN  - 0 (Slc39a8 protein, mouse)
RN  - 0 (T-Cell Acute Lymphocytic Leukemia Protein 1)
RN  - 0 (Tal1 protein, mouse)
SB  - IM
MH  - Anemia/*genetics
MH  - Animals
MH  - Cation Transport Proteins/*deficiency
MH  - Disease Models, Animal
MH  - Embryo, Mammalian
MH  - Female
MH  - GATA Transcription Factors/*metabolism
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation, Developmental
MH  - Gene Knockdown Techniques
MH  - Hematopoiesis/genetics
MH  - Hematopoietic Stem Cells/*metabolism
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Morphogenesis/genetics
MH  - Mouse Embryonic Stem Cells/metabolism
MH  - Pregnancy
MH  - Sequence Analysis, RNA
MH  - T-Cell Acute Lymphocytic Leukemia Protein 1/metabolism
MH  - Yolk Sac/cytology/metabolism
MH  - Zinc Fingers
PMC - PMC6048144
COIS- The authors declare no competing interests.
EDAT- 2018/07/18 06:00
MHDA- 2019/10/29 06:00
PMCR- 2018/07/16
CRDT- 2018/07/18 06:00
PHST- 2018/02/15 00:00 [received]
PHST- 2018/07/05 00:00 [accepted]
PHST- 2018/07/18 06:00 [entrez]
PHST- 2018/07/18 06:00 [pubmed]
PHST- 2019/10/29 06:00 [medline]
PHST- 2018/07/16 00:00 [pmc-release]
AID - 10.1038/s41598-018-29109-y [pii]
AID - 29109 [pii]
AID - 10.1038/s41598-018-29109-y [doi]
PST - epublish
SO  - Sci Rep. 2018 Jul 16;8(1):10703. doi: 10.1038/s41598-018-29109-y.