ZBTB38 is dispensable for antibody responses

Wong, Rachel; Bhattacharya, Deepta

doi:10.1371/journal.pone.0235183

Cited by 5 publications

(6 citation statements)

References 48 publications

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“…Pairwise comparisons revealed significantly increased expression of 33 genes in cluster 16 and 282 genes in cluster 33 relative to every other B-cell cluster (Table 4). Compared to other porcine B-cell clusters, cluster 16 had significantly greater expression of several genes associated with B-cell activation (such as BHL, ITGB7, JCHAIN, ZBTB38) (Castro and Flajnik, 2014;Kreslavsky et al, 2017;Delecluse et al, 2019;Wong and Bhattacharya, 2020), while many genes with significantly increased expression in cluster 33 were associated with cellular replication and/or division, such as HIST1H2AB, FIGURE 6 | Integration of porcine and human scRNA-seq datasets to further annotate porcine cells. (A) Mapping scores calculated to determine how well porcine cells were represented by the human dataset.…”

Section: Integration Of Porcine and Human Scrna-seq Datasets To Further Annotate Porcine Cellsmentioning

confidence: 99%

Reference Transcriptomes of Porcine Peripheral Immune Cells Created Through Bulk and Single-Cell RNA Sequencing

et al. 2021

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Pigs are a valuable human biomedical model and an important protein source supporting global food security. The transcriptomes of peripheral blood immune cells in pigs were defined at the bulk cell-type and single cell levels. First, eight cell types were isolated in bulk from peripheral blood mononuclear cells (PBMCs) by cell sorting, representing Myeloid, NK cells and specific populations of T and B-cells. Transcriptomes for each bulk population of cells were generated by RNA-seq with 10,974 expressed genes detected. Pairwise comparisons between cell types revealed specific expression, while enrichment analysis identified 1,885 to 3,591 significantly enriched genes across all 8 cell types. Gene Ontology analysis for the top 25% of significantly enriched genes (SEG) showed high enrichment of biological processes related to the nature of each cell type. Comparison of gene expression indicated highly significant correlations between pig cells and corresponding human PBMC bulk RNA-seq data available in Haemopedia. Second, higher resolution of distinct cell populations was obtained by single-cell RNA-sequencing (scRNA-seq) of PBMC. Seven PBMC samples were partitioned and sequenced that produced 28,810 single cell transcriptomes distributed across 36 clusters and classified into 13 general cell types including plasmacytoid dendritic cells (DC), conventional DCs, monocytes, B-cell, conventional CD4 and CD8 αβ T-cells, NK cells, and γδ T-cells. Signature gene sets from the human Haemopedia data were assessed for relative enrichment in genes expressed in pig cells and integration of pig scRNA-seq with a public human scRNA-seq dataset provided further validation for similarity between human and pig data. The sorted porcine bulk RNAseq dataset informed classification of scRNA-seq PBMC populations; specifically, an integration of the datasets showed that the pig bulk RNAseq data helped define the CD4CD8 double-positive T-cell populations in the scRNA-seq data. Overall, the data provides deep and well-validated transcriptomic data from sorted PBMC populations and the first single-cell transcriptomic data for porcine PBMCs. This resource will be invaluable for annotation of pig genes controlling immunogenetic traits as part of the porcine Functional Annotation of Animal Genomes (FAANG) project, as well as further study of, and development of new reagents for, porcine immunology.

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Section: Integration Of Porcine and Human Scrna-seq Datasets To Further Annotate Porcine Cellsmentioning

confidence: 99%

Reference Transcriptomes of Porcine Peripheral Immune Cells Created Through Bulk and Single-Cell RNA Sequencing

et al. 2021

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“…Wong et al generated Zbtb38 −/− mice using CRISPR/Cas9 technology in a C57BL/6 background. 50 The Zbtb38 fl/fl mice were crossed with CMV‐Cre mice expressing Cre recombinase ubiquitously under the control of a human cytomegalovirus promoter to obtain germline Zbtb38 deletion. Unexpectedly, Zbtb38 −/− mice were born, developed normally, and were fertile, with no detectable abnormalities of massive gene expression.…”

Section: Discussionmentioning

confidence: 99%

“…Wong et al generated Zbtb38 −/− mice using CRISPR/Cas9 technology in a C57BL/6 background 50 . The Zbtb38 fl/fl mice were crossed with CMV‐Cre mice expressing Cre recombinase ubiquitously under the control of a human cytomegalovirus promoter to obtain germline Zbtb38 deletion.…”

Section: Discussionmentioning

confidence: 99%

“…In support of this notion, loss of Zbtb38 altered the expression of genes critical for pluripotency, proliferation, differentiation and apoptosis. Our findings provide new insights for the understanding of a very low percentage of heterozygous embryonic lethality.Wong et al generated Zbtb38 À/À mice using CRISPR/Cas9 technology in a C57BL/6 background 50. The Zbtb38 fl/fl mice were crossed with CMV-Cre expressing Cre recombinase ubiquitously under the control of a human cytomegalovirus promoter to obtain germline Zbtb38 deletion.…”

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Heterozygous loss of Zbtb38 leads to early embryonic lethality via the suppression of Nanog and Sox2 expression

et al. 2022

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Objectives Mammalian DNA methyltransferases are essential to re‐establish global DNA methylation patterns during implantation, which is critical for transmitting epigenetic information to the next generation. In contrast, the significance of methyl‐CpG binding proteins (MBPs) that bind methylated CpG remains almost unknown at this stage. We previously demonstrated that Zbtb38 (also known as CIBZ)—a zinc finger type of MBP—is required for mouse embryonic stem (ES) cell proliferation by positively regulating Nanog expression. However, the physiological function of Zbtb38 in vivo remains unclear. Materials and Methods This study used the Cre‐loxP system to generate conditional Zbtb38 knockout mice. Cell proliferation and apoptosis were studied by immunofluorescence staining. Quantitative real‐time PCR, immunoblotting and immunofluorescence were performed to investigate the molecular mechanisms. Results Germline loss of the Zbtb38 single allele resulted in decreased epiblast cell proliferation and increased apoptosis shortly after implantation, leading to early embryonic lethality. Heterozygous loss of Zbtb38 reduced the expression of Nanog , Sox2 , and the genes responsible for epiblast proliferation, differentiation, and cell viability. Although this early lethal phenotype, Zbtb38 is dispensable for ES cell establishment and identity. Conclusions These findings indicate that Zbtb38 is essential for early embryonic development via the suppression of Nanog and Sox2 expression.

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“…Wong et al generated ZBTB38 -/- mice using CRISPR/Cas9 technology in a C57BL/6 background (Wong & Bhattacharya, 2020). The ZBTB38 fl/fl mice were crossed with CMV-Cre mice expressing Cre recombinase ubiquitously under the control of a human cytomegalovirus promoter to obtain germline ZBTB38 deletion.…”

Section: Discussionmentioning

confidence: 99%

Heterozygous loss of ZBTB38 leads to early embryonic lethality in mice via suppressing Nanog and Sox2

Matsuda

Nishio

Matsuura

et al. 2021

Preprint

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Mammalian DNA methylation is an epigenetic modification which is involved in various biological processes, including gene expression regulation. In mice, methyltransferases are responsible for DNA methylation, which are critical for early embryogenesis. However, the significance of methyl-CpG binding proteins (MBPs) that bind methylated CpG remains largely unknown. We previously demonstrated that ZBTB38/CIBZ-a zinc finger type of MBP-is required for ES cell proliferation by positively regulating Nanog expression. However, the physiological function of ZBTB38 remains unclear. In this study, we generated conditional ZBTB38 knockout mice using Cre-loxP technology. Unexpectedly, our results showed that germline loss of the ZBTB38 single allele resulted in decreased epiblast cell proliferation and increased apoptosis shortly after implantation, leading to early embryonic lethality. We found that heterozygous loss of ZBTB38 reduced the expression of Nanog, Sox2, and the genes responsible for epiblast proliferation, differentiation, and cell viability. Despite this lethal phenotype, ZBTB38 is dispensable for ES cell establishment and identity. Together, these findings indicate that ZBTB38 is essential for early embryonic development, providing new insights into the roles of MBP in implantation.

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ZBTB38 is dispensable for antibody responses

Cited by 5 publications

References 48 publications

Reference Transcriptomes of Porcine Peripheral Immune Cells Created Through Bulk and Single-Cell RNA Sequencing

Reference Transcriptomes of Porcine Peripheral Immune Cells Created Through Bulk and Single-Cell RNA Sequencing

Heterozygous loss of Zbtb38 leads to early embryonic lethality via the suppression of Nanog and Sox2 expression

Heterozygous loss of ZBTB38 leads to early embryonic lethality in mice via suppressing Nanog and Sox2

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