Publications by authors named "Nigel Michki"

Alveologenesis, the final stage in lung development, substantially remodels the distal lung, expanding the alveolar surface area for efficient gas exchange. Secondary crest myofibroblasts (SCMF) exist transiently in the neonatal distal lung and are crucial for alveologenesis. However, the pathways that regulate SCMF function, proliferation and temporal identity remain poorly understood.

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  • Hermansky-Pudlak syndrome (HPS) is a genetic disorder linked to pulmonary fibrosis, particularly in specific subtypes like HPS-1 and HPS-2, with studies showing mutant mice developing fibrosis as they age.
  • Research utilizing HPS mouse models and human lung tissue revealed dysfunction in alveolar epithelial type II (AT2) cells, including progressive loss and abnormal differentiation of these cells.
  • Transcriptomic analysis indicated that HPS AT2 cells have increased activation of genes related to abnormal differentiation and the p53 pathway, suggesting these pathways are crucial for understanding and potentially intervening in HPS-related pulmonary fibrosis.
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Introduction: Ataxia telangiectasia (A-T) is an autosomal recessive neurodegenerative disease with widespread systemic manifestations and marked variability in clinical phenotypes. In this study, we sought to determine whether transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) defines subsets of individuals with A-T beyond mild and classic phenotypes, enabling identification of novel features for disease classification and treatment response to therapy.

Methods: Participants with classic A-T (n = 77), mild A-T (n = 13), and unaffected controls (n = 15) were recruited from two outpatient clinics.

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  • Bacterial pneumonia can be more dangerous for newborns than for older kids, leading to serious health problems.
  • Researchers studied how the immune systems of baby mice and slightly older mice respond to pneumonia, measuring changes in their lungs over time.
  • They found that newborn mice had different immune cell responses compared to older mice, which helps explain why babies are more at risk for getting really sick from pneumonia.
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Bacterial pulmonary infections are a major cause of morbidity and mortality in neonates, with less severity in older children. Previous studies demonstrated that the DNA of CD4 T cells in the mouse lung, whose primary responsibility is to coordinate the immune response to foreign pathogens, is differentially methylated in neonates compared with juveniles. Nevertheless, the effect of this differential DNA methylation on CD4 T cell gene expression and response to infection remains unclear.

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There is a growing amount of data uncovering the cellular diversity of the pulmonary circulation and mechanisms governing vascular repair after injury. However, the molecular and cellular mechanisms contributing to the morphogenesis and growth of the pulmonary vasculature during embryonic development are less clear. Importantly, deficits in vascular development lead to significant pediatric lung diseases, indicating a need to uncover fetal programs promoting vascular growth.

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The study of neuron morphology requires robust and comprehensive methods to quantify the differences between neurons of different subtypes and animal species. Several software packages have been developed for the analysis of neuron tracing results stored in the standard SWC format. The packages, however, provide relatively simple quantifications and their non-extendable architecture prohibit their use for advanced data analysis and visualization.

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Identifying the cellular origins and mapping the dendritic and axonal arbors of neurons have been century old quests to understand the heterogeneity among these brain cells. Current Brainbow based transgenic animals take the advantage of multispectral labeling to differentiate neighboring cells or lineages, however, their applications are limited by the color capacity. To improve the analysis throughput, we designed Bitbow, a digital format of Brainbow which exponentially expands the color palette to provide tens of thousands of spectrally resolved unique labels.

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The Drosophila type II neuroblast lineages present an attractive model to investigate the neurogenesis and differentiation process as they adapt to a process similar to that in the human outer subventricular zone. We perform targeted single-cell mRNA sequencing in third instar larval brains to study this process of the type II NB lineage. Combining prior knowledge, in silico analyses, and in situ validation, our multi-informatic investigation describes the molecular landscape from a single developmental snapshot.

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Elucidating cell lineages provides crucial understanding of development. Recently developed sequencing-based techniques enhance the scale of lineage tracing but eliminate the spatial information offered by conventional approaches. Multi-spectral labeling techniques, such as Brainbow, have the potential to identify lineage-related cells in situ.

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