Abstract
Interferon‐induced transmembrane protein 1 (IFITM1), a member of the IFITM protein family, is a component of a multimeric complex involved in the transduction of antiproliferation and cell adhesion signals. IFITM1 is thought to play a role in antiproliferation and immune surveillance, and has been shown to restrict infection by numerous viruses. It is highly expressed in human embryonic stem cells (hESCs) but its role in hESCs remains to be elucidated. In this study, knockout of IFITM1 mediated by CRISPR/Cas9 in hESCs did not affect self‐renewal, pluripotency, telomerase activity or telomeres. However expression of human endogenous retroviruses (HERVs) was higher than in wild‐type hESCs, and there was also a reduced level of trimethylation of histone H3 on lysine 9 at HERV loci. These data show that IFITM1 suppresses HERVs in hESCs by regulating epigenetic modifications.
Highlights
Interferon-induced transmembrane protein 1 (IFITM1), known as interferon-inducible protein 9–27, CD225 and Leu13, is a cell surface molecule that is important for antiproliferative and homotypic adhesion signal transduction in lymphocytes [1,2]
We conducted immunofluorescence staining for IFITM3 in IFITM1 KO and WT human embryonic stem cell (hESC) to test the specificity of the sgRNAs used in the CRISPR/ Cas9 method
IFITM3 was found in both IFITM1 KO and WT hESCs by immunofluorescence (Fig. 1F), and there was no difference of IFITM3 levels between IFITM1 KO and WT hESCs shown by western blot (Fig. S1), further supporting that the designed sgRNAs were specific to IFITM1, consistent with the gene sequencing data
Summary
Interferon-induced transmembrane protein 1 (IFITM1), known as interferon-inducible protein 9–27, CD225 and Leu, is a cell surface molecule that is important for antiproliferative and homotypic adhesion signal transduction in lymphocytes [1,2]. IFITM1 could be highly induced by interferon-a and -c in response to infection by pathogens, and demonstrated antiviral activities, such as inhibition of influenza A replication and enveloped virus infection [3]. IFITM1 is up-regulated in human colorectal cancer (CRC) and has been. Abbreviations ChIP, chromatin immunoprecipitation; CRC, colorectal cancer; ERV, endogenous retrovirus; H3K9me, trimethylation of histone H3 on lysine 9; HEF, human embryonic fibroblast; HERV, human endogenous retrovirus; hESC, human embryonic stem cell; IFITM1, interferon-induced transmembrane protein 1; LTR, long terminal repeat; PGC, primordial germ cell; qRT-PCR, quantitative real-time PCR; TERT, telomerase reverse transcriptase; TRF, terminal restriction fragment. IFITM1 suppresses HERV expression in hESCs identified as a molecular marker in human colorectal tumors [13]. IFITM1 was found to be highly expressed in metastatic CRC cell lines as well as colorectal patient-derived tumor samples, and its high expression is associated with a poor prognosis of the disease [14,15], or a more advanced clinical stage [16]
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