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Purpose Of Review: Single-cell genomic approaches have uncovered cell fate biases and heterogeneity within hematopoietic subpopulations. However, standard single-cell transcriptomics suffers from high sampling noise, which particularly skews the distribution of lowly expressed genes, such as transcription factors (TFs). This might preclude the identification of rare transcripts that define cell identity and demarcate cell fate biases. Moreover, these studies need to go hand in hand with relevant functional assays to ensure that observed gene expression changes represent biologically meaningful alterations.
Recent Findings: Single-cell lineage tracing and functional validation studies have uncovered cell fate bias within transcriptionally distinct hematopoietic stem and progenitor subpopulations. Novel markers identified using these strategies have been proposed to prospectively isolate functionally distinct subpopulations, including long-term hematopoietic stem cells for ex vivo applications. Furthermore, the continuous nature of hematopoiesis has prompted the study of the relationship between stochastic transcriptional noise in hematopoietic TFs and cell fate determination.
Summary: An understanding of the limitations of single-cell genomic approaches and follow-up functional assays is critical to discern the technical and biological contribution of noise in hematopoietic heterogeneity, to identify rare gene expression states, and to uncover functionally distinct subpopulations within hematopoiesis.
Supplementary Video: http://links.lww.com/COH/A23.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169609 | PMC |
http://dx.doi.org/10.1097/MOH.0000000000000657 | DOI Listing |
Cell Mol Life Sci
December 2024
Department of Stem Cell Therapy Science, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
Macrophages are versatile myeloid leukocytes with flexible cellular states to perform diverse tissue functions beyond immunity. This plasticity is however often hijacked by diseases to promote pathology. Scanning kinetics of macrophage states by single-cell transcriptomics and flow cytometry, we observed atopic dermatitis drastically exhausted a resident subtype S1.
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January 2025
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA.
Investigating the molecular, cellular, and tissue-level changes caused by disease, and the effects of pharmacological treatments across these biological scales, necessitates the use of multiscale computational modeling in combination with experimentation. Many diseases dynamically alter the tissue microenvironment in ways that trigger microvascular network remodeling, which leads to the expansion or regression of microvessel networks. When microvessels undergo remodeling in idiopathic pulmonary fibrosis (IPF), functional gas exchange is impaired and lung function declines.
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November 2024
Department of Biology, Trivedi School of Biosciences, Ashoka University, No. 2 Rajiv Gandhi Educational City, Sonipat, Haryana 131029, India.
Biochemical signaling arising from mechanical force-induced physical changes in biological macromolecules is a critical determinant of key physiological processes across all biological lengths and time scales. Recent studies have deepened our understanding of how mechano-transduction regulates somatic tissues such as those in alveolar, gastrointestinal, embryonic, and skeleto-muscular systems. The germline of an organism has a heterogeneous composition - of germ cells at different stages of maturation and mature gametes, often supported and influenced by their accessory somatic tissues.
View Article and Find Full Text PDFDev Biol
December 2024
Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742 USA. Electronic address:
The trigeminal ganglion is a critical structure in the peripheral nervous system, responsible for transmitting sensations of touch, pain, and temperature from craniofacial regions to the brain. Trigeminal ganglion development depends upon intrinsic cellular programming as well as extrinsic signals exchanged by diverse cell populations. With its complex anatomy and dual cellular origin from cranial placodes and neural crest cells, the trigeminal ganglion offers a rich context for examining diverse biological processes, including cell migration, fate determination, adhesion, and axon guidance.
View Article and Find Full Text PDFAutoimmun Rev
December 2024
APC Microbiome Ireland, University College Cork, Ireland; College of Medicine and Health, University College Cork, Ireland.
T helper (Th) 17 and regulatory T (Treg) cells are highly plastic CD4 Th cell subsets, being able not only to actively adapt to their microenvironment, but also to interconvert, acquiring mixed identity markers. These phenotypic changes are underpinned by transcriptional control mechanisms, chromatin reorganization events and epigenetic modifications, that can be hereditable and stable over time. The Ikaros family of transcription factors have a predominant role in T cell subset specification through mechanisms of transcriptional program regulation that enable phenotypical diversification.
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