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  • Springer Nature  (4)
  • 2015-2019  (4)
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  • 1
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    Attenuation of PKC{delta} enhances metabolic activity and promotes expansion of blood progenitors (2018)
    Springer Nature
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    Publication Date: 2018
    Description: 〈p〉A finely tuned balance of self-renewal, differentiation, proliferation, and survival governs the pool size and regenerative capacity of blood-forming hematopoietic stem and progenitor cells (HSPCs). Here, we report that protein kinase C delta (PKC) is a critical regulator of adult HSPC number and function that couples the proliferative and metabolic activities of HSPCs. PKC-deficient mice showed a pronounced increase in HSPC numbers, increased competence in reconstituting lethally irradiated recipients, enhanced long-term competitive advantage in serial transplantation studies, and an augmented HSPC recovery during stress. PKC-deficient HSPCs also showed accelerated proliferation and reduced apoptosis, but did not exhaust in serial transplant assays or induce leukemia. Using inducible knockout and transplantation models, we further found that PKC acts in a hematopoietic cell-intrinsic manner to restrict HSPC number and bone marrow regenerative function. Mechanistically, PKC regulates HSPC energy metabolism and coordinately governs multiple regulators within signaling pathways implicated in HSPC homeostasis. Together, these data identify PKC as a critical regulator of HSPC signaling and metabolism that acts to limit HSPC expansion in response to physiological and regenerative demands.〈/p〉
    Print ISSN: 0261-4189
    Electronic ISSN: 1460-2075
    Topics: Biology , Medicine
    Published by Springer Nature on behalf of The European Molecular Biology Organization (EMBO).
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  • 2
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    Developmental and functional heterogeneity of white adipocytes within a single fat depot (2019)
    Springer Nature
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    Publication Date: 2019
    Description: 〈p〉Recent studies suggest that, even within a single adipose depot, there may be distinct subpopulations of adipocytes. To investigate this cellular heterogeneity, we have developed multiple conditionally immortalized clonal preadipocyte lines from white adipose tissue of mice. Analysis of these clones reveals at least three white adipocyte subpopulations. These subpopulations have differences in metabolism and differentially respond to inflammatory cytokines, insulin, and growth hormones. These also have distinct gene expression profiles and can be tracked by differential expression of three marker genes: Wilms’ tumor 1, transgelin, and myxovirus 1. Lineage tracing analysis with dual-fluorescent reporter mice indicates that these adipocyte subpopulations have differences in gene expression and metabolism that mirror those observed in the clonal cell lines. Furthermore, preadipocytes and adipocytes from these subpopulations differ in their abundance in different fat depots. Thus, white adipose tissue, even in a single depot, is comprised of distinct subpopulations of white adipocytes with different physiological phenotypes. These differences in adipocyte composition may contribute to the differences in metabolic behavior and physiology of different fat depots.〈/p〉
    Print ISSN: 0261-4189
    Electronic ISSN: 1460-2075
    Topics: Biology , Medicine
    Published by Springer Nature on behalf of The European Molecular Biology Organization (EMBO).
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  • 3
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    Developmental and functional heterogeneity of white adipocytes within a single fat depot (2018)
    Springer Nature
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    Publication Date: 2018
    Description: 〈sec〉〈st〉Synopsis〈/st〉〈p〉〈textbox textbox-type="graphic"〉〈p〉〈inline-fig〉〈/inline-fig〉〈/p〉〈/textbox〉〈/p〉 〈p〉While differences between white, beige and brown adipose tissues are relatively well studied, heterogeneity within white adipocytes remains unclear. Here, combined profiling and lineage tracing analyses identify distinct subpopulations of white fat cells even in a single pad, possibly explaining discrepant metabolic behavior and physiology of different depots.〈/p〉 〈p〉 〈l type="unord"〉〈li〉〈p〉Immortalized mouse preadipocyte cell lines display three white adipocyte subpopulations with differential gene expression and markers.〈/p〉〈/li〉 〈li〉〈p〉Adipocyte subpopulations differ in energy metabolism and response to inflammatory cytokines, insulin, and growth hormones.〈/p〉〈/li〉 〈li〉〈p〉The adipocyte subpopulations can be distinguished by expression of Wilms’ tumor 1, transgelin, and myxovirus 1.〈/p〉〈/li〉 〈li〉〈p〉Preadipocytes and adipocytes from these subpopulations show varying abundance in different fat depots 〈i〉in vivo〈/i〉.〈/p〉〈/li〉〈/l〉 〈/p〉〈/sec〉
    Print ISSN: 0261-4189
    Electronic ISSN: 1460-2075
    Topics: Biology , Medicine
    Published by Springer Nature on behalf of The European Molecular Biology Organization (EMBO).
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  • 4
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    Attenuation of PKC{delta} enhances metabolic activity and promotes expansion of blood progenitors (2018)
    Springer Nature
    Details
    Publication Date: 2018
    Description: 〈sec〉〈st〉Synopsis〈/st〉〈p〉〈textbox textbox-type="graphic"〉〈p〉〈inline-fig〉〈/inline-fig〉〈/p〉〈/textbox〉〈/p〉 〈p〉Hematopoietic stem and progenitor cells (HSPC) exert critical roles in the cell expansion required during homeostasis and regeneration of the blood system. Here, the protein kinase C delta (PKC) is shown to limit mouse HSPC output by controlling energy metabolism and hematopoietic differentiation.〈/p〉 〈p〉 〈l type="unord"〉〈li〉〈p〉PKC restricts HSPC pool size by restraining cell cycle progression and regulating apoptosis.〈/p〉〈/li〉 〈li〉〈p〉PKC deletion enhances recovery of HSPCs in settings of BM transplant and myelosuppression.〈/p〉〈/li〉 〈li〉〈p〉PKC deletion enhances metabolic activity of HSPCs.〈/p〉〈/li〉 〈li〉〈p〉PKC sets a threshold for HSPC activation and coordinately regulates multiple targets within progenitor cell signaling.〈/p〉〈/li〉〈/l〉 〈/p〉〈/sec〉
    Print ISSN: 0261-4189
    Electronic ISSN: 1460-2075
    Topics: Biology , Medicine
    Published by Springer Nature on behalf of The European Molecular Biology Organization (EMBO).
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