Dormancy, a reversible quiescent cellular state characterized by greatly reduced metabolic activity, protects from genetic damage, prolongs survival and is crucial for tissue homeostasis and cellular response to injury or transplantation. Dormant cells have been characterized in many tissues, but their identification, isolation and characterization irrespective of tissue of origin remains elusive. Here, we develop a live cell ratiometric fluorescent Optical Stem Cell Activity Reporter (OSCAR) based on the observation that phosphorylation of RNA Polymerase II (RNApII), a hallmark of active mRNA transcription elongation, is largely absent in dormant stem cells from multiple lineages. Using the small intestinal crypt as a model, OSCAR reveals in real time the dynamics of dormancy induction and cellular differentiation in vitro, and allows the identification and isolation of several populations of transcriptionally diverse OSCAR and OSCAR intestinal epithelial cell states in vivo. In particular, this reporter is able to identify a dormant OSCAR cell population in the small intestine. OSCAR therefore provides a tool for a better understanding of dormant stem cell biology.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175728 | PMC |
http://dx.doi.org/10.1038/s41467-021-23580-4 | DOI Listing |
Prostate cancer (PCa) is mainly managed with androgen deprivation therapy (ADT), but this often leads to a dormant state and subsequent relapse as lethal castration-resistant prostate cancer (CRPC). Using our unique PCa patient-derived xenograft (PDX) dormancy models, we investigated this critical dormant phase and discovered a selective increase in B7-H4 expression during the dormancy period following mouse host castration. This finding is supported by observations in clinical specimens of PCa patients treated with ADT.
View Article and Find Full Text PDFBlood
January 2025
Children's Hospital of Philadelphia & University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States.
Philadelphia chromosome-like B-cell acute lymphoblastic leukemia (Ph-like ALL) is driven by genetic alterations that induce constitutive kinase signaling and is associated with chemoresistance and high relapse risk in children and adults. Preclinical studies in the most common CRLF2-rearranged/JAK pathway-activated Ph-like ALL subtype have shown variable responses to JAK inhibitor-based therapies, suggesting incomplete oncogene addiction and highlighting a need to elucidate alternative biologic dependencies and therapeutic vulnerabilities, while the ABL-class Ph-like ALL subtype appears preferentially sensitive to SRC/ABL- or PDGFRB-targeting inhibitors. Which patients may be responsive versus resistant to tyrosine kinase inhibitor (TKI)-based precision medicine approaches remains a critical knowledge gap.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Institute of Sericulture and Tea, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China.
Bud dormancy is a critical adaptive trait in woody plants, essential for enduring harsh winter conditions. The relationship between bud break timing and cold resistance is complex and has been a subject of debate. This study utilizes a Genome-Wide Association Study (GWAS) on 201 natural mulberry populations to identify the gene, which shows the strongest association with bud break timing.
View Article and Find Full Text PDFGenome Biol
January 2025
College of Life Sciences, Key Laboratory of Animal Reproduction and Biotechnology in Universities of Shandong, Qingdao Agricultural University, Qingdao, 266109, China.
Background: In humans and other mammals, the process of oogenesis initiates asynchronously in specific ovarian regions, leading to the localization of dormant and growing follicles in the cortex and medulla, respectively; however, the current understanding of this process remains insufficient.
Results: Here, we integrate single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to comprehend spatial-temporal gene expression profiles and explore the spatial organization of ovarian microenvironments during early oogenesis in pigs. Projection of the germ cell clusters at different stages of oogenesis into the spatial atlas unveils a "cortical to medullary (C-M)" distribution of germ cells in the developing porcine ovaries.
Poult Sci
December 2024
Guangdong Engineering Laboratory for Medicament of Zoonosis Prevention and Control, Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, National Avian Influenza Para-Reference Laboratory (Guangzhou), College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. Electronic address:
Avian Influenza Virus (AIV) has been prevalent worldwide in recent years, resulting in substantial economic losses in the poultry industry. More importantly, AIV is capable of cross-species transmission among mammals, posing a dormant yet considerable threat to human health and safety. In this study, two rapid detection methods for AIV based on the CRISPR-Cas13a were developed.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!