AI Article Synopsis
Article Abstract
Transcriptional regulatory elements, including promoters and enhancers, play a key role in the cell-type specific regulation of the transcriptome. Application of rapidly evolving genetic tools, such as optogenetic/chemogenetic actuators and fluorescent reporters to elucidate the function of cell subtypes in vivo necessitates cell-type specific promoters or enhancers. In this context, methods for genome-wide functional screening of cis-regulatory elements, including enhancers, are of utmost importance. In this study, we describe a novel method for genome-wide functional screening of enhancer activity in vivo with minimal handling. Application of the method to cells from different brain structures and subsequent differential analysis allow identification of active enhancers in the target tissue or brain structures. To demonstrate proof of concept, we applied this method to samples from the dorsal raphe nucleus (DRN) and the medial prefrontal cortex of the mouse brain and successfully identified six enhancers with highly biased activity towards the dorsal raphe nucleus. Considering that these two structures consist of largely similar cell types whereas serotonin and dopamine neurons exist only in the DRN, our results confirm the validity of this method in identifying cell-type specific and brain-structure specific enhancers. Overall, this method will be helpful in identifying cis-regulatory elements suitable for cell-type specific manipulations.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1248/bpb.b22-00400 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Berberine Derivative B68 Promotes Tumor Immune Clearance by Dual-Targeting BMI1 for Senescence Induction and CSN5 for PD-L1 Degradation.
Adv Sci (Weinh)
December 2024
Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Promoting tumor cell senescence arrests the cell cycle of tumor cells and activates the immune system to eliminate these senescent cells, thereby suppressing tumor growth. Nevertheless, PD-L1 positive senescent tumor cells resist immune clearance and possess the ability to secret various cytokines and inflammatory factors that stimulate the growth of tumor cells. Consequently, drugs capable of both triggering senescence in tumor cells and concurrently diminishing the expression of PD-L1 to counteract immune evasion are urgently needed.
View Article and Find Full Text PDFThe GhANT-GoPGF module regulates pigment gland development in cotton leaves.
Cell Rep
December 2024
National Key Laboratory of Cotton Bio-breeding and Integrated Utilization, School of Life Science, Henan University, Kaifeng, Henan 475004, P.R. China. Electronic address:
Gossypium spp. pigment glands are a good model for studying plant secretory cavity structures. GoPGF (GOSSYPIUM PIGMENT GLAND FORMATION) is a well-characterized master transcription factor that controls gland formation in cotton; however, little is known about its transcriptional regulation.
View Article and Find Full Text PDFCell-type-specific auditory responses in the striatum are shaped by feedforward inhibition.
Cell Rep
December 2024
Department of Psychiatry and Neuroscience & Physiology, New York University Grossman School of Medicine, New York, NY 10016, USA. Electronic address:
The posterior "tail" region of the striatum receives dense innervation from sensory brain regions and is important for behaviors that require sensorimotor integration. The output neurons of the striatum, D1 and D2 striatal projection neurons (SPNs), which make up the direct and indirect pathways, are thought to play distinct functional roles, although it remains unclear if these neurons show cell-type-specific differences in their response to sensory stimuli. Here, we examine the strength of synaptic inputs onto D1 and D2 SPNs following the stimulation of upstream auditory pathways.
View Article and Find Full Text PDFItraconazole Reversing Acquired Resistance to Osimertinib in NSCLC by Inhibiting the SHH/DUSP13B/p-STAT3 Axis.
Adv Sci (Weinh)
December 2024
Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
There is an urgent necessity to devise efficient tactics to tackle the inevitable development of resistance to osimertinib, which is a third-generation epidermal growth factor receptor (EGFR) inhibitor used in treating EGFR-mutant nonsmall cell lung cancer (NSCLC). This study demonstrates that combining itraconazole with osimertinib synergistically reduces the proliferation and migration, enhances the apoptosis of osimertinib-resistant cells, and effectively inhibits the growth of osimertinib-resistant tumors. Mechanistically, itraconazole combined with osimertinib promotes the proteasomal degradation of sonic hedgehog (SHH), resulting in inactivation of the SHH/Dual-specificity phosphatase 13B (DUSP13B)/p-STAT3 and Hedgehog pathways, suppressing Myc proto-oncogene protein (c-Myc).
View Article and Find Full Text PDFLactylation of Histone H3k18 and Egr1 Promotes Endothelial Glycocalyx Degradation in Sepsis-Induced Acute Lung Injury.
Adv Sci (Weinh)
December 2024
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
Circulating lactate is a critical biomarker for sepsis-induced acute lung injury (S-ALI) and is strongly associated with poor prognosis. However, whether elevated lactate directly promotes S-ALI and the specific mechanism involved remain unclear. Here, this work shows that lactate causes pulmonary endothelial glycocalyx degradation and worsens ALI during sepsis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!