Ornithine decarboxylase 1 (ODC1 gene) has been linked through gain-of-function variants to a rare disease featuring developmental delay, alopecia, macrocephaly, and structural brain anomalies. ODC1 has been linked to additional diseases like cancer, with growing evidence for neurological contributions to schizophrenia, mood disorders, anxiety, epilepsy, learning, and suicidal behavior. The evidence of ODC1 connection to neural disorders highlights the need for a systematic analysis of ODC1 genotype-to-phenotype associations. An analysis of variants from ClinVar, Geno2MP, TOPMed, gnomAD, and COSMIC revealed an intellectual disability and seizure connected loss-of-function variant, ODC G84R (rs138359527, NC_000002.12:g.10444500C > T). The missense variant is found in ~1% of South Asian individuals and results in 2.5-fold decrease in enzyme function. Expression quantitative trait loci (eQTLs) reveal multiple functionally annotated, non-coding variants regulating ODC1 that associate with psychiatric/neurological phenotypes. Further dissection of RNA-Seq during fetal brain development and within cerebral organoids showed an association of ODC1 expression with cell proliferation of neural progenitor cells, suggesting gain-of-function variants with neural over-proliferation and loss-of-function variants with neural depletion. The linkage from the expression data of ODC1 in early neural progenitor proliferation to phenotypes of neurodevelopmental delay and to the connection of polyamine metabolites in brain function establish ODC1 as a bona fide neurodevelopmental disorder gene.

Idiopathic pulmonary fibrosis (IPF) is a pathological condition wherein lung injury precipitates the deposition of scar tissue, ultimately leading to a decline in pulmonary function. Existing research indicates a notable exacerbation in the clinical prognosis of IPF patients following infection with COVID-19. This investigation employed bulk RNA-sequencing methodologies to describe the transcriptomic profiles of small airway cell cultures derived from IPF and post-COVID fibrosis patients. Differential gene expression analysis unveiled heightened activation of pathways associated with microtubule assembly and interferon signaling in IPF cell cultures. Conversely, post-COVID fibrosis cell cultures exhibited distinctive characteristics, including the upregulation of pathways linked to extracellular matrix remodeling, immune system response, and TGF-β1 signaling. Notably, BMP signaling levels were elevated in cell cultures derived from IPF patients compared to non-IPF control and post-COVID fibrosis samples. These findings underscore the molecular distinctions between IPF and post-COVID fibrosis, particularly in the context of signaling pathways associated with each condition. A better understanding of the underlying molecular mechanisms holds the promise of identifying potential therapeutic targets for future interventions in these diseases.

Pulmonary fibrosis (PF) is a progressive and chronic lung disease characterized by repeated alveolar epithelial injury that leads to excessive extracellular matrix deposition, resulting in tissue thickening, scarring, and impaired gas exchange, leading to respiratory dysfunction. In the United States, around 50,000 new cases are reported annually, with patients facing serious complications such as pneumothorax, pulmonary hypertension, respiratory failure, and an increased risk of lung cancer. Current therapeutic options are limited in efficacy and primarily aim to slow disease progression. Cell therapy has emerged as a promising intervention, offering the potential to regenerate damaged lung tissue, modulate inflammation, and improve pulmonary function. However, the effectiveness of these therapies depends significantly on the ability to monitor the distribution, survival, and integration of transplanted cells within the host lungs. Magnetic Particle Imaging (MPI) is a novel, non-invasive, preclinical imaging modality that utilizes superparamagnetic iron oxide nanoparticles (SPIONs) as tracers. MPI offers high sensitivity, specificity, and no background signal, allowing for real-time and quantitative tracking of labeled cells in vivo. In this study, we investigated the use of MPI for monitoring human distal lung epithelial progenitor cells transplanted into the lungs of immunocompromised mice. Cells were labeled with varying SPION concentrations to optimize the signal, confirmed by immunostaining and iron quantification. After intratracheal instillation, 2D MPI scans were acquired to track the spatial distribution of transplanted cells. Longitudinal imaging over 2 weeks enabled visualization of cell integration and retention within lung tissue. Successful instillation exhibited MPI signals in both left and right lungs, which decreased (~65%) over time. Mice were subsequently sacrificed for histological validation. This study demonstrates the utility of MPI for noninvasive, longitudinal tracking of cell therapy in pulmonary fibrosis, and pivots around the intricate techniques utilized during the procedures.

Pulmonary fibrosis (PF) is a progressive and chronic lung disease characterized by repeated alveolar epithelial injury that leads to excessive extracellular matrix deposition, resulting in tissue thickening, scarring, and impaired gas exchange, leading to respiratory dysfunction. In the United States, around 50,000 new cases are reported annually, with patients facing serious complications such as pneumothorax, pulmonary hypertension, respiratory failure, and an increased risk of lung cancer. Current therapeutic options are limited in efficacy and primarily aim to slow disease progression. Cell therapy has emerged as a promising intervention, offering the potential to regenerate damaged lung tissue, modulate inflammation, and improve pulmonary function. However, the effectiveness of these therapies depends significantly on the ability to monitor the distribution, survival, and integration of transplanted cells within the host lungs. Magnetic Particle Imaging (MPI) is a novel, non-invasive, preclinical imaging modality that utilizes superparamagnetic iron oxide nanoparticles (SPIONs) as tracers. MPI offers high sensitivity, specificity, and no background signal, allowing for real-time and quantitative tracking of labeled cells in vivo. In this study, we investigated the use of MPI for monitoring human distal lung epithelial progenitor cells transplanted into the lungs of immunocompromised mice. Cells were labeled with varying SPION concentrations to optimize the signal, confirmed by immunostaining and iron quantification. After intratracheal instillation, 2D MPI scans were acquired to track the spatial distribution of transplanted cells. Longitudinal imaging over 2 weeks enabled visualization of cell integration and retention within lung tissue. Successful instillation exhibited MPI signals in both left and right lungs, which decreased (~65%) over time. Mice were subsequently sacrificed for histological validation. This study demonstrates the utility of MPI for noninvasive, longitudinal tracking of cell therapy in pulmonary fibrosis, and pivots around the intricate techniques utilized during the procedures.