Human resident liver macrophages protect against metabolic stress in obesity

Barreby, Emelie; Strunz, Benedikt; Azzimato, Valerio; Shen, Joanne X.; Naudet, Léa; Sönnerborg, Isabella; Sulen, André; Nock, Sebastian; Levi, Laura; Morgantini, Cecilia; Fardellas, Achilleas; Johansson, H; Nowak, Greg; Stål, Per; Ellis, Ewa; Näslund, Erik; Lauschke, Volker M.; Björkström, Niklas K.; Chen, Ping; Aouadi, Myriam

doi:10.1016/s0168-8278(22)01829-3

Cited by 2 publications

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“…[ 18,19 ] Furthermore, using liver spheroids we functionally dissected the crosstalk between hepatocytes and liver macrophages in MASLD [ 47,48 ] and could identify roles of subpopulations of myeloid in curbing hepatic metabolic stress in obesity. [ 49 ] However, comprehensive phenotypic profiling of this model at the proteome level had so far been limited due to the high cell numbers required for conventional proteomics. Importantly, we here found that protein extraction using repeated freeze‐thaw cycles was identified to outperform chemical lysis methods by over 40%.…”

Section: Discussionmentioning

confidence: 99%

Proteomic workflows for deep phenotypic profiling of 3D organotypic liver models

Koutsilieri,

Mickols,

Végvári

et al. 2024

Biotechnology Journal

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Organotypic human tissue models constitute promising systems to facilitate drug discovery and development. They allow to maintain native cellular phenotypes and functions, which enables long‐term pharmacokinetic and toxicity studies, as well as phenotypic screening. To trace relevant phenotypic changes back to specific targets or signaling pathways, comprehensive proteomic profiling is the gold‐standard. A multitude of proteomic workflows have been applied on 3D tissue models to quantify their molecular phenotypes; however, their impact on analytical results and biological conclusions in this context has not been evaluated. The performance of twelve mass spectrometry‐based global proteomic workflows that differed in the amount of cellular input, lysis protocols and quantification methods was compared for the analysis of primary human liver spheroids. Results differed majorly between protocols in the total number and subcellular compartment bias of identified proteins, which is particularly relevant for the reliable quantification of transporters and drug metabolizing enzymes. Using a model of metabolic dysfunction‐associated steatotic liver disease, we furthermore show that critical disease pathways are robustly identified using a standardized high throughput‐compatible workflow based on thermal lysis, even using only individual spheroids (1500 cells) as input. The results increase the applicability of proteomic profiling to phenotypic screens in organotypic microtissues and provide a scalable platform for deep phenotyping from limited biological material.

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Section: Discussionmentioning

confidence: 99%

Proteomic workflows for deep phenotypic profiling of 3D organotypic liver models

Koutsilieri,

Mickols,

Végvári

et al. 2024

Biotechnology Journal

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“…Human organs are populated by resident myeloid and lymphoid immune cells with a composition that differs between tissues, likely due to distinct anatomical factors and environmental cues (1)(2)(3). Compared to the dogma from murine parabiosis models where tissue residency is long-lasting (4), solid organ transplantation studies in humans have revealed an alternative picture with a greater degree of immune cell reconstitution over time (5)(6)(7)(8). However, the reconstitution rate appears to be organ and cell-type specific with more rapid reconstitution of liver myeloid and lymphoid cells (7,8) whilst intraepithelial T cells remain donor-derived for longer periods of time after lung and intestinal transplantation (5,6,9) as well as of host origin in skin after hematopoietic stem cell transplantation (HSCT) (10).…”

Section: Introductionmentioning

confidence: 99%

Reconstitution of the uterine immune milieu after transplantation

Strunz,

Ivarsson,

Sun

et al. 2024

Preprint

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Maintenance of tissue-specific immunity is important for immunological fitness, but its establishment have been difficult to assess in humans. Here, we investigated reconstitution of the human uterine immune system by studying women undergoing uterus solid organ transplantation (UTX) or hematopoietic stem cell transplantation (HSCT). Through single-cell identification based on SNPs and disparate HLA expression using single-cell RNA sequencing or high-parameter flow cytometry, donor vs recipient cell origin was determined, and features of these cells were studied. A full uterine immune cell reconstitution occurred after both UTX and HSCT, both at transcriptomic and phenotypic level. This occurred despite tacrolimus-induced calcineurin-mediated NFAT pathway inhibition, which affected de novo induction of tissue-residency features in vitro. Intriguingly, after HSCT, immune cells of male origin could reconstitute the uterine immune milieu. Collectively, our results proved insights into tissue immune system persistence and reconstitution capabilities in an organ undergoing continuous regeneration.

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Human resident liver macrophages protect against metabolic stress in obesity

Cited by 2 publications

References 0 publications

Proteomic workflows for deep phenotypic profiling of 3D organotypic liver models

Proteomic workflows for deep phenotypic profiling of 3D organotypic liver models

Reconstitution of the uterine immune milieu after transplantation

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