Prdm12 is a key transcription factor in nociceptor neurogenesis. Mutations of Prdm12 cause congenital insensitivity to pain (CIP) from failure of nociceptor development. However, precisely how deletion of Prdm12 during development or adulthood affects nociception is unknown. Here, we employ tissue- and temporal-specific knockout mouse models to test the function of Prdm12 during development and in adulthood. We find that constitutive loss of Prdm12 causes deficiencies in proliferation during sensory neurogenesis. We also demonstrate that conditional knockout from dorsal root ganglia (DRGs) during embryogenesis causes defects in nociception. In contrast, we find that, in adult DRGs, Prdm12 is dispensable for most pain-sensation and injury-induced hypersensitivity. Using transcriptomic analysis, we find mostly unique changes in adult Prdm12 knockout DRGs compared with embryonic knockout and that PRDM12 is likely a transcriptional activator in the adult. Overall, we find that the function of PRDM12 changes over developmental time.
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http://dx.doi.org/10.1016/j.celrep.2021.108913 | DOI Listing |
Mol Ther Oncol
December 2024
Department of Clinical Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Immunotherapy has transformed the management of hepatocellular carcinoma (HCC), but effectiveness varies among patients. This study aimed to identify biomarkers and HCC subtypes responsive to immunotherapy. Patients were classified into Immunity-High (Immunity-H) and Immunity-Low (Immunity-L) subtypes using ssGSEA scores.
View Article and Find Full Text PDFUnited European Gastroenterol J
November 2024
Reproductive Medicine Center, The First Affiliated Hospital of Naval Medical University, Shanghai, China.
Background: Methylated stool DNA (sDNA) is a reliable noninvasive biomarker for early colorectal cancer (CRC) diagnosis. However, there are barely any diagnostic panels that can achieve both a sensitivity and specificity exceeding 90% simultaneously.
Objective: We aimed to identify a novel methylated sDNA panel and model for the early diagnosis of CRC.
BMC Bioinformatics
July 2024
Department of Health Data Science and Artificial Intelligence, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, 7000 Fannin Street, Houston, TX, USA.
Neural Dev
January 2024
ULB Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB), Gosselies, B- 6041, Belgium.
Prdm12 is an epigenetic regulator expressed in developing and mature nociceptive neurons, playing a key role in their specification during neurogenesis and modulating pain sensation at adulthood. In vitro studies suggested that Prdm12 recruits the methyltransferase G9a through its zinc finger domains to regulate target gene expression, but how Prdm12 interacts with G9a and whether G9a plays a role in Prdm12's functional properties in sensory ganglia remain unknown. Here we report that Prdm12-G9a interaction is likely direct and that it involves the SET domain of G9a.
View Article and Find Full Text PDFiScience
December 2023
Department of Molecular Biology, ULB Neuroscience Institute (UNI), Université libre de Bruxelles (ULB), B-6041 Gosselies, Belgium.
Prdm12 is a transcriptional regulator essential for the emergence of the somatic nociceptive lineage during sensory neurogenesis. The exact mechanisms by which Prdm12 promotes nociceptor development remain, however, poorly understood. Here, we report that the trigeminal and dorsal root ganglia hypoplasia induced by the loss of involves Bax-dependent apoptosis and that it is accompanied by the ectopic expression of the visceral sensory neuron determinants and , which is, however, not sufficient to impose a complete fate switch in surviving somatosensory neurons.
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