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Expression of Piwi protein MIWI2 defines a distinct population of multiciliated cells

ABSTRACT: We find that MIWI2 protein is expressed in a discrete population of multiciliated airway epithelial cells of the lung. The isolation and the next generation sequencing of the MIWI2-positive multiciliated cells revealed that they are phenotypically distinct from neighboring MIWI2-negative multiciliated cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE101806 | GEO | 2017/09/19

SECONDARY ACCESSION(S): PRJNA395563

REPOSITORIES: GEO

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Expression of Piwi protein MIWI2 defines a distinct population of multiciliated cells.

Project description: Not available

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RNAseq profiling of multiciliated cells

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MIWI2 and MILI have differential effects on piRNA biogenesis and DNA methylation

2015-07-11 | GSE70731 | GEO

RNAseq and ChIPseq profiling of Foxn4 and Foxj1 in multiciliated cells

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Exonuclease domain-containing 1 enhances MIWI2 piRNA biogenesis via its interaction with TDRD12

Project description:PIWI proteins and their associated small RNAs called PIWI-interacting RNAs (piRNAs) restrict transposon activity in animal gonads to ensure fertility. Distinct biogenesis pathways load piRNAs into the PIWI proteins MILI and MIWI2 in the mouse male embryonic germline. While most of MILI piRNAs derive via a slicer-independent pathway, a MILI slicer endonuclease-initiated pathway loads nuclear MIWI2 with a series of phased piRNAs. Tudor domain-containing 12 (TDRD12) and its interaction partner Exonuclease domain-containing 1 (EXD1) are required for loading MIWI2, but only Tdrd12 is essential for fertility, leaving us with no explanation for the physiological role of Exd1. Using an artificial piRNA precursor, we demonstrate that MILI-triggered piRNA biogenesis is greatly reduced in the Exd1 mutant. The situation deteriorates in the sensitized Exd1 mutant (Exd1-/-; Tdrd12+/-), where diminished MIWI2 piRNA levels de-repress LINE1 retrotransposons, causing infertility. Thus, EXD1 enhances slicing-triggered MIWI2 piRNA biogenesis via a functional interaction with TDRD12.

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Expression data of kidney multiciliated cells from zebrafish embryos

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MIWI2 and MILI have differential effects on piRNA biogenesis and DNA methylation

Project description:In developing male germ cells, prospermatogonia, two Piwi proteins, MILI and MIWI2, use piRNA guides to repress transposable element (TE) expression and ensure genome stability and proper gametogenesis. In addition to their roles in post-transcriptional TE repression, both proteins are required for DNA methylation of TE sequences. Here we analyzed the effect of Miwi2 deficiency on piRNA biogenesis and transposon repression. Miwi2-deficiency had only a minor impact on piRNA biogenesis; however, the piRNA profile of Miwi2-knockout mice indicated overexpression of several LINE1 TE families that led to activation of the ping-pong piRNA cycle. Furthermore, we found that MILI and MIWI2 have distinct functions in TE repression in the nucleus. MILI is responsible for DNA methylation of a larger subset of TE families than MIWI2 suggesting that the proteins have independent roles in establishing DNA methylation patterns. Small RNA profiles (19-30 nt range) of embryonic (E16.5) and post-natal (P10) testis of Miwi2 mutant mice and matched heterozygote controls. mRNA profiles of embryonic testis (E16.5) of heterozygote control mice and of postnatal testis (P10) of Miwi2 and Mili mutants and heterozygote controls. CpG methylation BS-seq profile of postnatal (P10) spermatocytes of Miwi2 mutant mice and matched heterozygote controls.

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TEX15 is an essential executor of MIWI2-directed transposon DNA methylation and silencing.

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Project description:Allergic inflammation affects the epithelial cell populations resulting in goblet cell hyperplasia and decreased ciliated cells. In this study, we aimed to investigate the effect of allergic inflammation in nasal epithelial cell transcriptomes at the single-cell level. We performed scRNAseq in cultured primary human nasal epithelial (HNE) cells and in vivo nasal epithelium. The transcriptomic features and epithelial cell subtypes were determined under IL-4 stimulation, and cell-specific marker genes and proteins were identified. We confirmed that cultured HNE cells were similar to in vivo epithelial cells through scRNAseq. Cell-specific marker genes were utilized to cluster the cell subtypes, and FOXJ1+ -ciliated cells were sub-classified into multiciliated and deuterosomal cells. PLK4 and CDC20B were specific for deuterosomal cells, and SNTN, CPASL, and GSTA2 were specific for multiciliated cells. IL-4 altered the proportions of cell subtypes, resulting in a decrease in multiciliated cells and loss of deuterosomal cells. The trajectory analysis revealed deuterosomal cells as precursor cells of multiciliated cells and deuterosomal cells function as a bridge between club and multiciliated cells. A decrease in deuterosomal cell marker genes was observed in nasal tissue samples with type 2 inflammation.The effects of IL-4 appear to be mediated through the loss of the deuterosomal population, resulting in the reduction in multiciliated cells. This study also newly suggests cell-specific markers that might be pivotal for investigating respiratory inflammatory diseases.

2023-11-21 | GSE245392 | GEO

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