Partial beta cell loss induces transient compensatory proliferation I
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PROVIDER: PRJNA1079817 | ENA |
REPOSITORIES: ENA
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Project description:Partial beta cell loss induces transient compensatory proliferation II
| PRJNA1079820 | ENA
Project description:Loss of functional β-cells is a pivotal event in the dysregulation of glucose homeostasis observed in diabetes. While the plasticity of β-cells in response to increased metabolic demand has been extensively studied, the common drivers of β-cell proliferation and the molecular mechanisms governing regeneration in humans remain elusive. Here, we investigated the proliferative response following targeted chemical ablation of β-cells using diphtheria toxin (DT) and streptozotocin (STZ) in mice. Hemizygous expression of the RIP-DTR transgene enabled efficient partial ablation of β-cells, leading to close to 50% β-cell loss five days post ablation, stabilizing at this level up to 10 weeks post ablation. Transcriptomic analysis revealed a dynamic molecular landscape following ablation, with early activation of tissue remodeling and clearance of dead cells, followed by transient activation of regenerative signaling pathways. Furthermore, we observed a distinct proliferative boost in the immediate aftermath of ablation, characterized by upregulation of cell cycle progression markers. Interestingly, long-term follow-up revealed compound stress from partial β-cell loss and high-fat diet feeding induced a robust proliferative response, albeit with a negative impact on β-cell signature. Additionally, single low-dose STZ injections induced partial β-cell loss and compensatory proliferation, with the regulatory landscape deregulated by STZ injection in the long term. The compound stress of high-fat diet and STZ ablation further altered the islet transcriptional landscape, particularly affecting metabolic pathways. Overall, our study provides insights into the dynamic response of β-cells to partial ablation and highlights the impact of compound stressors on islet function and metabolism, shedding light on potential strategies for promoting β-cell regeneration in diabetes. Loss of functional β-cells is a pivotal event in the dysregulation of glucose homeostasis observed in diabetes. While the plasticity of β-cells in response to increased metabolic demand has been extensively studied, the common drivers of β-cell proliferation and the molecular mechanisms governing regeneration in humans remain elusive. Here, we investigated the proliferative response following targeted chemical ablation of β-cells using diphtheria toxin (DT) and streptozotocin (STZ) in mice. Hemizygous expression of the RIP-DTR transgene enabled efficient partial ablation of β-cells, leading to close to 50% β-cell loss five days post ablation, stabilizing at this level up to 10 weeks post ablation. Transcriptomic analysis revealed a dynamic molecular landscape following ablation, with early activation of tissue remodeling and clearance of dead cells, followed by transient activation of regenerative signaling pathways. Furthermore, we observed a distinct proliferative boost in the immediate aftermath of ablation, characterized by upregulation of cell cycle progression markers. Interestingly, long-term follow-up revealed compound stress from partial β-cell loss and high-fat diet feeding induced a robust proliferative response, albeit with a negative impact on β-cell signature. Additionally, single low-dose STZ injections induced partial β-cell loss and compensatory proliferation, with the regulatory landscape deregulated by STZ injection in the long term. The compound stress of high-fat diet and STZ ablation further altered the islet transcriptional landscape, particularly affecting metabolic pathways. Overall, our study provides insights into the dynamic response of β-cells to partial ablation and highlights the impact of compound stressors on islet function and metabolism, shedding light on potential strategies for promoting β-cell regeneration in diabetes. Loss of functional β-cells is a pivotal event in the dysregulation of glucose homeostasis observed in diabetes. While the plasticity of β-cells in response to increased metabolic demand has been extensively studied, the common drivers of β-cell proliferation and the molecular mechanisms governing regeneration in humans remain elusive. Here, we investigated the proliferative response following targeted chemical ablation of β-cells using diphtheria toxin (DT) and streptozotocin (STZ) in mice. Hemizygous expression of the RIP-DTR transgene enabled efficient partial ablation of β-cells, leading to close to 50% β-cell loss five days post ablation, stabilizing at this level up to 10 weeks post ablation. Transcriptomic analysis revealed a dynamic molecular landscape following ablation, with early activation of tissue remodeling and clearance of dead cells, followed by transient activation of regenerative signaling pathways. Furthermore, we observed a distinct proliferative boost in the immediate aftermath of ablation, characterized by upregulation of cell cycle progression markers. Interestingly, long-term follow-up revealed compound stress from partial β-cell loss and high-fat diet feeding induced a robust proliferative response, albeit with a negative impact on β-cell signature. Additionally, single low-dose STZ injections induced partial β-cell loss and compensatory proliferation, with the regulatory landscape deregulated by STZ injection in the long term. The compound stress of high-fat diet and STZ ablation further altered the islet transcriptional landscape, particularly affecting metabolic pathways. Overall, our study provides insights into the dynamic response of β-cells to partial ablation and highlights the impact of compound stressors on islet function and metabolism, shedding light on potential strategies for promoting β-cell regeneration in diabetes.
2025-02-28 | GSE256518 | GEO
Project description:Loss of functional β-cells is a pivotal event in the dysregulation of glucose homeostasis observed in diabetes. While the plasticity of β-cells in response to increased metabolic demand has been extensively studied, the common drivers of β-cell proliferation and the molecular mechanisms governing regeneration in humans remain elusive. Here, we investigated the proliferative response following targeted chemical ablation of β-cells using diphtheria toxin (DT) and streptozotocin (STZ) in mice. Hemizygous expression of the RIP-DTR transgene enabled efficient partial ablation of β-cells, leading to close to 50% β-cell loss five days post ablation, stabilizing at this level up to 10 weeks post ablation. Transcriptomic analysis revealed a dynamic molecular landscape following ablation, with early activation of tissue remodeling and clearance of dead cells, followed by transient activation of regenerative signaling pathways. Furthermore, we observed a distinct proliferative boost in the immediate aftermath of ablation, characterized by upregulation of cell cycle progression markers. Interestingly, long-term follow-up revealed compound stress from partial β-cell loss and high-fat diet feeding induced a robust proliferative response, albeit with a negative impact on β-cell signature. Additionally, single low-dose STZ injections induced partial β-cell loss and compensatory proliferation, with the regulatory landscape deregulated by STZ injection in the long term. The compound stress of high-fat diet and STZ ablation further altered the islet transcriptional landscape, particularly affecting metabolic pathways. Overall, our study provides insights into the dynamic response of β-cells to partial ablation and highlights the impact of compound stressors on islet function and metabolism, shedding light on potential strategies for promoting β-cell regeneration in diabetes. Loss of functional β-cells is a pivotal event in the dysregulation of glucose homeostasis observed in diabetes. While the plasticity of β-cells in response to increased metabolic demand has been extensively studied, the common drivers of β-cell proliferation and the molecular mechanisms governing regeneration in humans remain elusive. Here, we investigated the proliferative response following targeted chemical ablation of β-cells using diphtheria toxin (DT) and streptozotocin (STZ) in mice. Hemizygous expression of the RIP-DTR transgene enabled efficient partial ablation of β-cells, leading to close to 50% β-cell loss five days post ablation, stabilizing at this level up to 10 weeks post ablation. Transcriptomic analysis revealed a dynamic molecular landscape following ablation, with early activation of tissue remodeling and clearance of dead cells, followed by transient activation of regenerative signaling pathways. Furthermore, we observed a distinct proliferative boost in the immediate aftermath of ablation, characterized by upregulation of cell cycle progression markers. Interestingly, long-term follow-up revealed compound stress from partial β-cell loss and high-fat diet feeding induced a robust proliferative response, albeit with a negative impact on β-cell signature. Additionally, single low-dose STZ injections induced partial β-cell loss and compensatory proliferation, with the regulatory landscape deregulated by STZ injection in the long term. The compound stress of high-fat diet and STZ ablation further altered the islet transcriptional landscape, particularly affecting metabolic pathways. Overall, our study provides insights into the dynamic response of β-cells to partial ablation and highlights the impact of compound stressors on islet function and metabolism, shedding light on potential strategies for promoting β-cell regeneration in diabetes. Loss of functional β-cells is a pivotal event in the dysregulation of glucose homeostasis observed in diabetes. While the plasticity of β-cells in response to increased metabolic demand has been extensively studied, the common drivers of β-cell proliferation and the molecular mechanisms governing regeneration in humans remain elusive. Here, we investigated the proliferative response following targeted chemical ablation of β-cells using diphtheria toxin (DT) and streptozotocin (STZ) in mice. Hemizygous expression of the RIP-DTR transgene enabled efficient partial ablation of β-cells, leading to close to 50% β-cell loss five days post ablation, stabilizing at this level up to 10 weeks post ablation. Transcriptomic analysis revealed a dynamic molecular landscape following ablation, with early activation of tissue remodeling and clearance of dead cells, followed by transient activation of regenerative signaling pathways. Furthermore, we observed a distinct proliferative boost in the immediate aftermath of ablation, characterized by upregulation of cell cycle progression markers. Interestingly, long-term follow-up revealed compound stress from partial β-cell loss and high-fat diet feeding induced a robust proliferative response, albeit with a negative impact on β-cell signature. Additionally, single low-dose STZ injections induced partial β-cell loss and compensatory proliferation, with the regulatory landscape deregulated by STZ injection in the long term. The compound stress of high-fat diet and STZ ablation further altered the islet transcriptional landscape, particularly affecting metabolic pathways. Overall, our study provides insights into the dynamic response of β-cells to partial ablation and highlights the impact of compound stressors on islet function and metabolism, shedding light on potential strategies for promoting β-cell regeneration in diabetes.
2025-02-28 | GSE256517 | GEO
Project description:TRIM21 knockout mouse livers show enhanced antioxidant capacity and decreased compensatory proliferation
| PRJNA690122 | ENA
Project description:Partial reprogramming restores youthful gene expression through transient suppression of cell identity
| PRJNA735380 | ENA
Project description:Liver regeneration is an well orchestrated compensatory process that regulated by multiple factors. We recently reported the importance of chromatin protein, a high-mobility group box 2 (HMGB2) in mouse liver regeneration, however, it’s molecular mechanism is not yet understood. In this study, we aimed to study how HMGB2 regulates hepatocyte proliferation during liver regeneration. Wild-type (WT) and HMGB2-knockout (KO) mice were 70% partial hepatectomized (PHx), and liver tissues were analyzed by microarray, immunohistochemistry, qPCR and western blotting. In vivo experimental findings were confirmed by in vitro experiments using HMGB2 gene knockdown in combination with de novo lipogenesis model. In WT mouse, HMGB2-positive hepatocytes were co-localized with cell proliferation markers, whereas, hepatocyte proliferation was significantly decreased in HMGB2-KO mice. Oil red-O staining detected the transient accumulation of lipid droplets at 12-24 h in WT mouse livers, however, decreased amount of lipid droplets were found in HMGB2-KO mouse livers, and it was prolonged until 36 h. Microarray, immunohistochemistry and qPCR results were demonstrated that lipid metabolism related genes were significantly decreased in HMGB2-KO mouse livers. In vitro experiments demonstrated that decreased lipid droplets in HMGB2-knockdown cells correlated with decreased cell proliferation activity. HMGB2 is involved in the regulation of liver regeneration through transient accumulation of lipid droplets in hepatocytes.
2023-10-14 | GSE244551 | GEO
Project description:A major question in developmental and regenerative biology is how organ size is controlled by progenitor cells. For example, while limb bones exhibit catch-up growth (recovery of a normal growth trajectory after transient developmental perturbation), it is unclear how this emerges from the behaviour of chondroprogenitors, the cells sustaining the cartilage anlagen that are progressively replaced by bone. Here we show that transient sparse cell death in the mouse foetal cartilage was repaired postnatally, via a two-step process. During injury, progression of chondroprogenitors towards more differentiated states was delayed, leading to altered cartilage cytoarchitecture and impaired bone growth. Then, once cell death was over, chondroprogenitor differentiation was accelerated and cartilage structure recovered, including partial rescue of bone growth. At the molecular level, ectopic activation of mTORC1 correlated with, and was necessary for, part of the recovery, revealing a specific candidate to be explored during normal growth and in future therapies.
2024-03-11 | GSE235779 | GEO
Project description:Transient loss of Polycomb components induces an epigenetic cancer fate
| PRJNA918577 | ENA
Project description:While the thyroid has the capacity to grow in response to a stimulus that perturbs the pituitary-thyroid axis, cells involved in this process have not been well characterized. In this study, partial thyroidectomy was used to produce regeneration. Histological and gene profiling analyses were carried out using normal mouse thyroid as well as those after partial thyroidectomy. In the central area of the right or left normal thyroid lobe, a proliferative center was found with the occasional presence of micro-follicles, where BrdU-positive and/or C cells were mainly localized. Two weeks after partial thyroidectomy, the number of BrdU-positive cells and cells with clear or faintly eosionphilic cytoplasm, markedly increased in the central area of the thyroid lobe and the overlapping area close to the cutting edge. Clear-looking cells had scant cytoplasmic components as determined by electron microscopy; some retained characteristic features of C cells such as the presence of neuroendocrine granules while others retained follicular cell specific features such as those directly facing a lumen with microvilli at the apical side of the cell. Some of the clear-looking cells were BrdU-positive and expressed FOXA2, the definitive endoderm lineage marker. Microarray analysis further revealed that partial thyroidectomy affected the expression pattern of genes involved in cellular and/or metabolic process and their regulation categorized as Endocrine System Disorders and Embryonic Development, by Pathway analysis. These results suggest that cells previously C cells and/or follicular cells may be altered after partial thyroidectomy to become immature cells that participate in the repair and/or regeneration of the thyroid, a process similar to embryonic thyroid development. Total RNAs used for microarray analysis were prepared from laser capture microdissected mouse thyroids of the central (C) and peripheral (P) areas before (N: normal) and after (D: dissected) partial thyroidectomy. The RNAs obtained were first amplified, which were then subjected to hybridization using 5 NC (central area of the right or left lobe of normal thyroid), 3 NP (peripheral area of the right or left lobe of normal thyroid), 5DC (central area of the right or left lobe of dissected thyroid), 5 DP (peripheral area of the right or left lobe of dissected thyroid), and universal mouse RNAs as a reference. The 4-way analysis was carried out: NC vs NP vs DC vs DP.
2012-04-01 | E-GEOD-25934 | biostudies-arrayexpress
Project description:Transient induction of pluripotent reprogramming factors has been reported to reverse some features of aging in mammalian cells and tissues. However, the impact of transient reprogramming on somatic cell identity programs and the necessity of individual pluripotency factors remain unknown. Here, we mapped trajectories of transient reprogramming in young and aged cells from multiple murine cell types using single cell transcriptomics to address these questions. We found that transient reprogramming restored youthful gene expression in adipogenic cells and mesenchymal stem cells but also temporarily suppressed somatic cell identity programs. We further screened Yamanaka Factor subsets and found that many combinations had an impact on aging gene expression and suppressed somatic identity, but that these effects were not tightly entangled. We also found that a transient reprogramming approach inspired by amphibian regeneration restored youthful gene expression in aged myogenic cells. Our results suggest that transient pluripotent reprogramming poses a neoplastic risk, but that restoration of youthful gene expression can be achieved with alternative strategies.
2022-06-10 | GSE176206 | GEO