S100A6 is a critical regulator of hematopoietic stem cells

Grahn, Tan Hooi Min; Niroula, Abhishek; Végvári, Ákos; Oburoglu, Leal; Pertesi, Maroulio; Warsi, Sarah; Safi, Fatemeh; Miharada, Natsumi; Garcia, Sandra Capellera; Siva, Kavitha; Liu, Yang; Rörby, Emma; Nilsson, Björn; Zubarev, Roman A.; Karlsson, Stefán

doi:10.1038/s41375-020-0901-2

Cited by 21 publications

(15 citation statements)

References 54 publications

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“…In addition, the S100 family of proteins are associated with inflammatory pathways in the brain connected to aging-related diseases such as Alzheimer's disease 27 . A recent study discovered an S100 protein to be a critical regulator of hematopoietic stem cell renewal through mitochondrial metabolic regulation and function 42 . In rats, recombinant S100A4 demonstrates an anti-apoptotic function in response to oxidative stress injury 43 .…”

Section: Discussionmentioning

confidence: 99%

Multi-modal profiling of peripheral blood cells across the human lifespan reveals distinct immune cell signatures of aging and longevity

Karagiannis

Dowrey

Villacorta‐Martin

et al. 2022

Preprint

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Age-related changes in immune cell composition and functionality are associated with multimorbidity and mortality. However, many centenarians delay the onset of aging-related disease suggesting the presence of elite immunity that remains highly functional at extreme old age. To identify immune-specific patterns of aging and extreme human longevity, we analyzed novel single cell profiles from the peripheral blood mononuclear cells (PBMCs) of 7 centenarians (mean age 106) and publicly available single cell RNA-sequencing (scRNA-seq) datasets that included an additional 7 centenarians as well as 52 people at younger ages (20-89 years). The analysis confirmed known shifts in the ratio of lymphocytes to myeloid cells, and noncytotoxic to cytotoxic cell distributions with aging, but also identified significant shifts from CD4+ T cell to B cell populations in centenarians suggesting a history of exposure to natural and environmental immunogens. Our transcriptional analysis identified cell type signatures specific to exceptional longevity that included genes with age-related changes (e.g., increased expression of STK17A, a gene known to be involved in DNA damage response) as well as genes expressed uniquely in centenarians PBMCs (e.g., S100A4, part of the S100 protein family studied in age-related disease and connected to longevity and metabolic regulation). Collectively, these data suggest that centenarians harbor unique, highly functional immune systems that have successfully adapted to a history of insults allowing for the achievement of exceptional longevity.

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Section: Discussionmentioning

confidence: 99%

Multi-modal profiling of peripheral blood cells across the human lifespan reveals distinct immune cell signatures of aging and longevity

Karagiannis

Dowrey

Villacorta‐Martin

et al. 2022

Preprint

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“… 80 Further, Nrf2-regulated S100a6, which is significantly increased in Txnrd1 -deficient β-cells, plays a role in stem cell renewal. 81 Additional studies are necessary to determine the mechanism utilized by Txnrd1 -knockout β-cells to establish and maintain mass.…”

Section: Discussionmentioning

confidence: 99%

Deletion of Thioredoxin Reductase Disrupts Redox Homeostasis and Impairs β-Cell Function

et al. 2022

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Reactive oxygen species (ROS) have been implicated as mediators of pancreatic β-cell damage. While β-cells are thought to be vulnerable to oxidative damage, we have shown, using inhibitors and acute depletions, that thioredoxin reductase, thioredoxin, and peroxiredoxins are the primary mediators of antioxidant defense in β-cells. However, the role of this antioxidant cycle in maintaining redox homeostasis and β-cell survival in vivo remains unclear. Here, we generated mice with a β-cell specific knockout of thioredoxin reductase 1 (Txnrd1fl/fl; Ins1Cre/+, βKO). Despite blunted glucose-stimulated insulin secretion, knockout mice maintain normal whole body glucose homeostasis. Unlike pancreatic islets with acute Txnrd1 inhibition, βKO islets do not demonstrate increased sensitivity to ROS. RNA-sequencing analysis revealed that Txnrd1-deficient β-cells have increased expression of Nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated genes, and altered expression of genes involved in heme and glutathione metabolism, suggesting an adaptive response. Txnrd1-deficient β-cells also have decreased expression of factors controlling β-cell function and identity which may explain the mild functional impairment. Together, these results suggest that Txnrd1-knockout β-cells compensate for loss of this essential antioxidant pathway by increasing expression of Nrf2-regulated antioxidant genes, allowing for protection from excess ROS at the expense of normal β-cell function and identity.

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“…In rule 7, which was used in distinguishing Class 5 (cholangiocyte), S100A6, GSTA1, and NOCA7 showed low expression levels, whereas QSOX1, BTG1 showed high expression levels. S100A6 plays a regulatory role in a variety of cell differentiation processes and has a low expression level in terminally differentiated cholangiocytes ( Grahn et al, 2020 ). Given that high BTG1 expression inhibits cell proliferation and differentiation, cholangiocytes were presumed to have reached a stable state.…”

Section: Discussionmentioning

confidence: 99%

Identifying In Vitro Cultured Human Hepatocytes Markers with Machine Learning Methods Based on Single-Cell RNA-Seq Data

Huang²,

Chen³

et al. 2022

Front. Bioeng. Biotechnol.

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Cell transplantation is an effective method for compensating for the loss of liver function and improve patient survival. However, given that hepatocytes cultivated in vitro have diverse developmental processes and physiological features, obtaining hepatocytes that can properly function in vivo is difficult. In the present study, we present an advanced computational analysis on single-cell transcriptional profiling to resolve the heterogeneity of the hepatocyte differentiation process in vitro and to mine biomarkers at different periods of differentiation. We obtained a batch of compressed and effective classification features with the Boruta method and ranked them using the Max-Relevance and Min-Redundancy method. Some key genes were identified during the in vitro culture of hepatocytes, including CD147, which not only regulates terminally differentiated cells in the liver but also affects cell differentiation. PPIA, which encodes a CD147 ligand, also appeared in the identified gene list, and the combination of the two proteins mediated multiple biological pathways. Other genes, such as TMSB10, TMEM176B, and CD63, which are involved in the maturation and differentiation of hepatocytes and assist different hepatic cell types in performing their roles were also identified. Then, several classifiers were trained and evaluated to obtain optimal classifiers and optimal feature subsets, using three classification algorithms (random forest, k-nearest neighbor, and decision tree) and the incremental feature selection method. The best random forest classifier with a 0.940 Matthews correlation coefficient was constructed to distinguish different hepatic cell types. Finally, classification rules were created for quantitatively describing hepatic cell types. In summary, This study provided potential targets for cell transplantation associated liver disease treatment strategies by elucidating the process and mechanism of hepatocyte development at both qualitative and quantitative levels.

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S100A6 is a critical regulator of hematopoietic stem cells

Cited by 21 publications

References 54 publications

Multi-modal profiling of peripheral blood cells across the human lifespan reveals distinct immune cell signatures of aging and longevity

Multi-modal profiling of peripheral blood cells across the human lifespan reveals distinct immune cell signatures of aging and longevity

Deletion of Thioredoxin Reductase Disrupts Redox Homeostasis and Impairs β-Cell Function

Identifying In Vitro Cultured Human Hepatocytes Markers with Machine Learning Methods Based on Single-Cell RNA-Seq Data

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