Microscopic examination of spatial transcriptome using Seq-Scope

Cell, Journal Year: 2021, Volume and Issue: 184(13), P. 3559 - 3572.e22

Published: June 1, 2021

Language: Английский

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A long-term study of AAV gene therapy in dogs with hemophilia A identifies clonal expansions of transduced liver cells

Nature Biotechnology, Journal Year: 2020, Volume and Issue: 39(1), P. 47 - 55

Published: Nov. 16, 2020

Language: Английский

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Aneuploidy as a promoter and suppressor of malignant growth

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(2), P. 89 - 103

Published: Jan. 11, 2021

Language: Английский

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Polygenic enrichment distinguishes disease associations of individual cells in single-cell RNA-seq data

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(10), P. 1572 - 1580

Published: Sept. 1, 2022

Language: Английский

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Understanding Nanomaterial–Liver Interactions to Facilitate the Development of Safer Nanoapplications

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(11)

Published: Jan. 14, 2022

Nanomaterials (NMs) are widely used in commercial and medical products, such as cosmetics, vaccines, drug carriers. Exposure to NMs via various routes dermal, inhalation, ingestion has been shown gain access the systemic circulation, resulting accumulation of liver. The unique organ structures blood flow features facilitate liver sequestration NMs, which may cause adverse effects Currently, most vivo studies focused on at level evaluation gross changes structure functions, however, cell-type-specific uptake responses, well molecular mechanisms cellular levels leading lagging. Herein, authors systematically review diverse interactions with liver, specifically major cell types including Kupffer cells (KCs), sinusoidal endothelial (LSECs), hepatic stellate (HSCs), hepatocytes detailed involved. In addition, knowledge gained nano-liver that can development safer nanoproducts nanomedicine is also reviewed.

Language: Английский

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Proliferative polyploid cells give rise to tumors via ploidy reduction

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Jan. 28, 2021

Abstract Polyploidy is a hallmark of cancer, and closely related to chromosomal instability involved in cancer progression. Importantly, polyploid cells also exist some normal tissues. Polyploid hepatocytes proliferate dynamically reduce their ploidy during liver regeneration. This raises the question whether proliferating polyploids are prone via chromosome missegregation mitosis and/or reduction. Conversely could be resistant tumor development due redundant genomes. Therefore, tumor-initiation risk physiologic polyploidy reduction still unclear. Using vivo lineage tracing we here show that readily form tumors frequent give rise regenerative nodules with aberrations, which enhanced by Although should theoretically prevent suppressor loss, high frequency negates this protection. undergo multiple rounds cell division become predominantly mononucleated Our results suggest an early step initiation carcinogenesis from hepatocytes.

Language: Английский

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Single-nucleus RNA-seq2 reveals functional crosstalk between liver zonation and ploidy

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: July 12, 2021

Abstract Single-cell RNA-seq reveals the role of pathogenic cell populations in development and progression chronic diseases. In order to expand our knowledge on cellular heterogeneity, we have developed a single-nucleus RNA-seq2 method tailored for comprehensive analysis nuclear transcriptome from frozen tissues, allowing dissection all types present liver, regardless size or fragility. We use this approach characterize transcriptional profile individual hepatocytes with different levels ploidy, discovered that ploidy states are associated metabolic potential, gene expression tetraploid mononucleated is conditioned by their position within hepatic lobule. Our work remarkable crosstalk between dosage spatial distribution hepatocytes.

Language: Английский

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Polyploidy as a Fundamental Phenomenon in Evolution, Development, Adaptation and Diseases

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3542 - 3542

Published: March 24, 2022

DNA replication during cell proliferation is ‘vertical’ copying, which reproduces an initial amount of genetic information. Polyploidy, results from whole-genome duplication, a fundamental complement to vertical copying. Both organismal and polyploidy can emerge via premature cycle exit or cell-cell fusion, the latter giving rise polyploid hybrid organisms epigenetic hybrids somatic cells. Polyploidy-related increase in biological plasticity, adaptation, stress resistance manifests evolution, development, regeneration, aging, oncogenesis, cardiovascular diseases. Despite prevalence nature importance for medicine, agri- aquaculture, processes mechanisms underlying these features largely remain unknown. The evolutionarily conserved include activation transcription, response stress, damage hypoxia, induction programs morphogenesis, unicellularity, longevity, suggesting that common confer adaptive viability, cells organisms. By increasing polyploidization provide survival under stressful conditions where diploid cannot survive. However, it occurs at expense specific function, thus promoting developmental programming adult diseases risk cancer. Notably, genes arising evolutionary are heavily involved cancer other Ploidy-related changes gene expression presumably originate chromatin modifications derepression bivalent genes. provided evidence elucidates role carcinogenesis, may contribute development new strategies regeneration preventing

Language: Английский

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Diploid hepatocytes drive physiological liver renewal in adult humans

Cell Systems, Journal Year: 2022, Volume and Issue: 13(6), P. 499 - 507.e12

Published: May 31, 2022

Physiological liver cell replacement is central to maintaining the organ's high metabolic activity, although its characteristics are difficult study in humans. Using retrospective radiocarbon (14C) birth dating of cells, we report that human hepatocytes show continuous and lifelong turnover, allowing remain a young organ (average age <3 years). Hepatocyte renewal highly dependent on ploidy level. Diploid more than 7-fold higher annual rates polyploid hepatocytes. These observations support view physiological humans mainly diploid hepatocytes, whereas cells compromised their ability divide. Moreover, cellular transitions between limited under homeostatic conditions. With these findings, present an integrated model generation provides fundamental insights into turnover dynamics.

Language: Английский

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Polyploid tubular cells: a shortcut to stress adaptation

Kidney International, Journal Year: 2024, Volume and Issue: 105(4), P. 709 - 716

Published: Jan. 9, 2024

Tubular epithelial cells (TC) compose the majority of kidney parenchyma and play fundamental roles in maintaining homeostasis. Like other tissues, mostly immature TC with progenitor capabilities are able to replace lost during injury via clonal expansion differentiation. In contrast, differentiated lack this capacity. However, as is frequently exposed toxic injuries, evolution positively selected a response program that endows maintain residual function injury. Recently, we others have described polyploidization TC, mechanism augment remnant after an by rapid hypertrophy. Polyploidy condition characterized more than two complete sets chromosomes. Polyploid often display increased functional capacity generally resilient stress evidenced being conserved across many plants eukaryote species from flies mammals. Here, discuss occurrence polyploidy different contexts conditions how integrates into existing concepts cell responses Collectively, aim at stimulating acquisition novel knowledge field well accelerating translation basic clinical sphere.

Language: Английский

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