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Transcriptome analyses of intestine-specific Slc39a8-KO mice

ABSTRACT: Transcriptome analyses of intestine-specific Slc39a8-KO mice

PROVIDER: PRJNA792728 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17345054_1.fastq.gz	Fastqsanger.gz
	SRR17345054_2.fastq.gz	Fastqsanger.gz
	SRR17345055_1.fastq.gz	Fastqsanger.gz
	SRR17345055_2.fastq.gz	Fastqsanger.gz
	SRR17345056_1.fastq.gz	Fastqsanger.gz

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Transcriptome analyses of intestine-specific Slc39a8-KO mice

Project description:Purpose: To identify genes whose expression was altered in the intestinal epithelial cells (IECs) of Slc39a8-KO mice. Methods: Poly(A) RNA-seq Results: We identified four genes that showed changes in their expression in the Slc39a8-KO IECs.

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Neuronal SLC39A8 deficiency impairs cerebellar development and function by dysregulating brain Mn homeostasis

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Project description:Tumorigenesis in different segments of the intestinal tract involves tissue-specific oncogenic drivers. In the colon, complement component 3 (C3) activation is a major contributor to inflammation and malignancies. By contrast, tumorigenesis in the small intestine involves fatty acid-binding protein 1 (FABP1). However, little is known of the upstream mechanisms driving their expressions in different segments of the intestinal tract. Here, we report that an RNA binding protein DDX5 augments C3 and FABP1 expressions post-transcriptionally to promote tumorigenesis in the colon and small intestine, respectively. Mice with epithelial-specific knockout of DDX5 are protected from intestine tumorigenesis. The identification of DDX5 as the common upstream regulator of tissue-specific oncogenic molecules provides a new therapeutic target for intestine cancers.

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Project description:The human ZRT/IRT-like protein 8 (ZIP8), encoded by the solute carrier family 39 member 8 gene SLC39A8, is a metal cation symporter located mainly on the cell membrane. ZIP8 is well-known for its role in transporting divalent metal ions into the cells – these ions include several essential micronutrients (e.g., iron [Fe], manganese [Mn], and zinc [Zn]) and non-essential toxic heavy metal cadmium (Cd). In the current project, ZIP8 gene in the human cervical cancer HeLa cell line was knockout (KO) using the CRISPR/Cas9 genome editing technology. Then, the proteomes of ZIP8-KO HeLa cell line and HeLa parental cell line (with wildtype ZIP8 gene sequence) were quantified using iTRAQ and LC-MS/MS.

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Project description: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.

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