Project description:Expression profiling of Prdm1 mutant E18.5 small intestine was performed using Illumina whole genome V2 arrays. The hypothesis tested in the present study was that Blimp1 regulates the transcription of key genes involved in enterocyte differentiation and survival. Results identify substantial and premature activation of key components of the adult enterocyte biochemical signature. Villin-Cre and Prdm1BEH/+ animals were intercrossed to generate heterozygous Villin-Cre, Prdm1BEH males that were then mated with homozygous Prdm1 CA/CA females carrying the R26R allele to generate Prdm1+/+ (Prdm1CA/+) or Prdm1-/- (Villin-Cre, Prdm1CA/BEH) offspring. Total RNA obtained from 11 Prdm1+/+ and 10 Prdm1-/- E18.5 small intestine samples was hybridized to Illumina WG6_V2 beadchips.
Project description:Expression profiling of wild-type and Prdm1 null mouse trophoblast giant cell cultures using Illumina whole genome mouse V2 arrays. The hypothesis tested was that Prdm1/Blimp1 regulates expression of genes required for spiral artery trophoblast giant cell function. Prdm1 null and littermate control wild-type trophoblast stem cell clones were generated from blastocyst outgrowths. Total RNA was obtained from multiple replicates of four wild-type TS cell clones and four Prdm1 null TS cell clones differenitated for zero, two, four and six days by growth factor withdrawal and hybridized to Illumina WG6_V2 arrays
Project description:We reports the transcript landscape of PR Domain Containing 1, with ZNF domain (PRDM1) in RKO colon cancer cells. We show that PRDM1 alpha and PRDM1 beta transcript isoforms repress and activate a largely overlapping suite of genes, many of which belong to the embryonic stem cell core transcript program.
Project description:Interleukin-21 (IL-21) is a pleiotropic cytokine that induces expression of transcription factor BLIMP1 (encoded by Prdm1), which regulates plasma cell differentiation and T cell homeostasis. We identified an IL-21 response element downstream of Prdm1 that binds the transcription factors STAT3 and IRF4, which are required for optimal Prdm1 expression. Genome-wide ChIP-Seq mapping of STAT3- and IRF4-binding sites showed that most regions with IL-21-induced STAT3 binding also bound IRF4 in vivo, and furthermore, revealed that the noncanonical TTCnnnTAA GAS motif critical in Prdm1 was broadly used for STAT3 binding. Comparing genome-wide expression array data to binding sites revealed that most IL-21-regulated genes were associated with combined STAT3-IRF4 sites rather than pure STAT3 sites. Correspondingly, ChIP-Seq analysis of Irf4_/_ T cells showed greatly diminished STAT3 binding after IL-21 treatment, and Irf4_/_ mice showed impaired IL- 21-induced Tfh cell differentiation in vivo. These results reveal broad cooperative gene regulation by STAT3 and IRF4. Affymetrix expression data: Prepare CD4+ T cells from spleen. CD4+ T cells were preactivated, rested, and treated with IL-21 for 1, 6, and 24 hours. ChIP-seq data: Profiling of IRF4 and Stat3 binding with and without IL-21 stimulation in wild type and IRF4 KO mice.
Project description:Our goal was to transcriptionally profile Prdm1+ cell lineages of maternal and embryonic origin in mid-gestation mouse placenta in order to study vascular mimicry and additional processes in the placenta. Profiling of 61 single cells and 17 clusters of 2 or 3 cells chosen based on expression of Prdm1, a paternally inherited Prdm1-Venus fluorescent reporter, progenitor trophoblast marker Gjb3 and spiral artery trophoblast giant cell marker Prl7b1.
Project description:Expression profiling of wild-type and Prdm1 null mouse trophoblast giant cell cultures using Illumina whole genome mouse V2 arrays. The hypothesis tested was that Prdm1/Blimp1 regulates expression of genes required for spiral artery trophoblast giant cell function.
Project description:Dysregulation of genetic pathways during germ cell development leads to infertility and tumorigenesis. Here, we used high throughput analyses in bona fide human primordial germ cells (hPGCs) to probe the genetics of human germ cell specification and differentiation and uncover redistribution of OCT4 protein occupancy relative to human embryonic stem cells (hESCs). We demonstrate that the developmental programs from pluripotent stem cell to germ cell formation and differentiation are driven by switching partners with OCT4 protein from SOX2 to PAX5 and PRDM1. Genetic gain- and loss-of-function studies reveal that PAX5 encodes a novel and critical regulator of human germ cell development. Moreover, analysis of epistasis indicates that PAX5 acts upstream, binding to enhancers of OCT4 and PRDM1, to regulate expression during differentiation. The PAX5-OCT4-PRDM1 proteins form a core transcriptional network that activates germline and represses somatic genetic programs. Broadly, these findings also illustrate the power of combined human gene editing, cell differentiation and engraftment for directly probing the genetics of human developmental stages that have historically been difficult to study.
Project description:The mechanisms of transcriptional regulation underlying human primordial germ cell differentiation are largely unknown. Transcriptional repressor Prdm1/Blimp1 is known to play a critical role in controlling germ cell specification in mice. We show that ectopic expression of PRDM1 in hESCs promotes the generation of cells exhibiting transcriptomic features of early primordial germ cells.
Project description:Persistence of infused antitumor T cells is one of the essential factors for durable therapeutic response. T cells undergo genome-wide alterations in epigenetic architecture upon repeated antigen encounter, which is inevitably accompanied by progressive T cell differentiation and loss of longevity. In this study, we explored key epigenetic factors associated with terminal T cell differentiation using CRISPR/Cas9-mediated knockout of epigenetic genes in chimeric antigen receptor (CAR)-engineered human T cells and identified PRDM1 as one of the key epigenetic genes regulating T cell differentiation. We compared epigenetic profiles of control and PRDM1-knockout CAR-T cells by ATAC-sequencing analysis.
Project description:Prdm1 encodes the transcriptional repressor PRDM1/BLIMP1 and Prdm1 mutant mice are one of the rare mutant strains that do not develop whisker hair follicles while still displaying a pelage. We demonstrate that Lef1, a key mediator of the Wnt/Beta Catenin pathway, acts upstream of Prdm1 and identify a primate specific deletion of a Lef1 enhancer, Leaf. This loss may have been significant in the evolutionary process, leading to the progressive defunctionalization and disappearance of vibrissae in primates.