Publications by authors named "D S Garfield"
-regulatory elements (CREs), such as promoters and enhancers, are DNA sequences that regulate the expression of genes. The activity of a CRE is influenced by the order, composition, and spacing of sequence motifs that are bound by proteins called transcription factors (TFs). Synthetic CREs with specific properties are needed for biomanufacturing as well as for many therapeutic applications including cell and gene therapy.
View Article and Find Full Text PDFWound healing in response to acute injury is mediated by the coordinated and transient activation of parenchymal, stromal, and immune cells that resolves to homeostasis. Environmental, genetic, and epigenetic factors associated with inflammation and aging can lead to persistent activation of the microenvironment and fibrosis. Here, we identify opposing roles of interleukin-4 (IL-4) cytokine signaling in interstitial macrophages and type II alveolar epithelial cells (ATIIs).
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- Stem cells play a crucial role in maintaining rapidly renewing tissues like blood and intestines, and mutations affecting their proliferation and differentiation can lead to serious health issues.
- Researchers conducted studies by genetically targeting Rho-kinases Rock1 and Rock2 in adult mice, discovering these enzymes are essential for the health of hematopoietic (blood-forming) and gastrointestinal systems.
- Mice lacking Rho-kinases experienced cell cycle arrest in blood progenitors and impaired gut epithelial renewal, highlighting the importance of these kinases for stem cell function and overall organ integrity.
DNA accessibility of -regulatory elements (CREs) dictates transcriptional activity and drives cell differentiation during development. While many genes regulating embryonic development have been identified, the underlying CRE dynamics controlling their expression remain largely uncharacterized. To address this, we produced a multimodal resource and genomic regulatory map for the zebrafish community, which integrates single-cell combinatorial indexing assay for transposase-accessible chromatin with high-throughput sequencing (sci-ATAC-seq) with bulk histone PTMs and Hi-C data to achieve a genome-wide classification of the regulatory architecture determining transcriptional activity in the 24-h post-fertilization (hpf) embryo.
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- Cellular senescence and the senescence-associated secretory phenotype (SASP) are linked to aging and related diseases, negatively affecting tissue health through inflammation.
- The study uses intestinal organoids to demonstrate that SASP factors from senescent fibroblasts disrupt stem cell function, leading to impaired tissue regeneration.
- A specific protein, the secreted N-terminal domain of Ptk7, is identified as crucial in this process, activating signals that hinder stem cell differentiation and contribute to age-related tissue dysfunction.