Project description:Intestinal stem cells are required for proliferation, differentiation, and regeneration of the intestinal epithelium. Krüppel-like factor 5 regulates intestinal stem cells in both physiologic and pathological conditions and may be a treatment target in certain diseases of the intestine.
Project description:Under conditions of hormonal adjuvant treatment the estrogen receptor apoprotein supports breast cancer cell cycling through the retinoic acid receptor α1 apoprotein. Basal proliferation persisted in estrogen-sensitive breast cancer cells grown in hormone depleted conditioned media without or with 4-hydroxytamoxifen (OH-Tam). Downregulating ER using siRNA inhibited basal proliferation by promoting cell cycle arrest. The basal expression of RARα1, the only RARα isoform that was expressed in breast cancer cell lines and in most breast tumors, was supported by apo-ER but was unaffected by OH-Tam. The overlapping tamoxifen-insensitive gene regulation by apo-ER and apo-RARα1 comprised activation of mainly genes promoting cell cycle and mitosis and suppression of genes involved in growth inhibition.
Project description:The small intestine has a robust regenerative capacity, and various cell types serve as “cells-of-origin” in the epithelial regeneration process after injury. However, how much each population contributes to regeneration remains unclear. Using lineage tracing, we found that Lgr5-expressing cells’ derivatives contained radioresistant ISCs crucial for epithelial regeneration in the damaged intestine after radiation. Single-cell RNA sequencing analysis of Lgr5-derivatives identified primary source of epithelial regeneration in the irradiation damaged intetsine.
Project description:Under conditions of hormonal adjuvant treatment the estrogen receptor apoprotein supports breast cancer cell cycling through the retinoic acid receptor M-NM-11 apoprotein. Basal proliferation persisted in estrogen-sensitive breast cancer cells grown in hormone depleted conditioned media without or with 4-hydroxytamoxifen (OH-Tam). Downregulating ER using siRNA inhibited basal proliferation by promoting cell cycle arrest. The basal expression of RARM-NM-11, the only RARM-NM-1 isoform that was expressed in breast cancer cell lines and in most breast tumors, was supported by apo-ER but was unaffected by OH-Tam. The overlapping tamoxifen-insensitive gene regulation by apo-ER and apo-RARM-NM-11 comprised activation of mainly genes promoting cell cycle and mitosis and suppression of genes involved in growth inhibition. Cells were plated at 20% confluence in low glucose phenol red free medium supplemented with 5% charcoal stripped FBS and glutamine 24h-48h prior to transfection. Treatment with vehicle, OH-Tam (100nM), or OH-Tam (500nM) was begun an additional 24h later. Cells were transfected with control siRNA, ERM-NM-1 siRNA or RARM-NM-1 siRNA.
Project description:Lp(a) and its distinguishing apolipoprotein constituent apo(a) have been shown to elicit proinflammatory responses from monocytes and macrophages. To obtain a global picture of the effect of Lp(a) and apo(a) on the transcriptome of these cells, we treated THP-1 macrophages with 250 nM Lp(a) or apo(a) for 6 hours, harvested RNA from the cells, and then performed RNA-seq using an Illumina NextSeq instrument. Analysis of the data using GO and KEGG strategies revealed a series of proinflammatory genes upregulated by apo(a) and even more dramatically by Lp(a).
Project description:TMT-Based quantitative proteomic analysis reveals the key role of metabolic process, cell proliferation and apoptosis in intestine regeneration of Apostichopus japonicus
Project description:We aimed to evaluate changes in expression in control and th1/th1 mice treated with PBS and apo-transferrin to understand the effect(s) of exogenous apo-transferrin on normal and ineffective erythropoiesis
Project description:The cellular origin of intestinal epithelial regeneration has been a subject of continued debate, with recent models challenging the primacy of WNT-dependent LGR5⁺ crypt base columnar (CBC) cells as the central regenerative population. Here, we revisit this question through quantitative integration of single-cell transcriptomic, chromatin accessibility, spatial, and lineage-tracing analyses across the proximal-to-distal axis of the small intestinal epithelium. Our data show that under homeostatic conditions, LGR5⁺ cells exclusively sustain epithelial self-renewal in nearly all crypt–villus units along the entire length of the small intestine. Following irradiation or chemotoxic injury, surviving LGR5⁺ CBC cells and their immediate progeny undergo transcriptional and epigenetic reprogramming into transient fetal-like cell states that initiate epithelial repair. Crucially, successful regeneration depends on the reactivation of canonical WNT/β-catenin signaling, as evidenced by increased TCF motif accessibility and upregulation of WNT target genes, including Lgr5. Accordingly, pharmacological inhibition of WNT signaling blocks the reconstitution of LGR5⁺ cells and crypt regeneration, leading to epithelial collapse. These findings reconcile prior controversies by demonstrating that epithelial regeneration throughout the small intestine, even following injury, is ultimately driven by LGR5⁺ CBC cells in a WNT-dependent manner.
