Multilayer omics analysis reveals a non-classical retinoic acid signaling axis that regulates hematopoietic stem cell identity

Schönberger, Katharina; Obier, Nadine; Romero-Mulero, Mari Carmen; Cauchy, Pierre; Mess, Julian; Pavlovich, Polina V.; Zhang, Yu Wei; Mitterer, Michael; Rettkowski, Jasmin; Lalioti, Maria‐Eleni; Jäcklein, Karin; Curtis, Jonathan D.; Féret, Betty; Sommerkamp, Pia; Morganti, Claudia; Ito, Keisuke; Ghyselinck, Norbert B.; Trompouki, Eirini; Buescher, Joerg M.; Pearce, Erika L.; Cabezas-Wallscheid, Nina

doi:10.1016/j.stem.2021.10.002

Cited by 57 publications

(52 citation statements)

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“…The endogenous agonist, RA, is metabolized to 4-oxo-RA and 4-OH-RA by the cytochrome P450 enzymes Cyp26a1 and Cyp26b1; 4-oxo- and 4-OH-RA have biological activity, but data show that these retinoids are generally further metabolized in a catabolic pathway that inactivates these ligands [ 38 , 39 , 40 , 41 ]. However, production of 4-oxo-RA by Cyp26b1 was recently shown to be required to maintain hematopoietic stem cells’ identity, and depletion of dietary vitamin A in animals resulted in a dysfunctional stemness phenotype in hematopoietic stem cells [ 42 ]. Notably, we showed that embryonic stem cells (ESCs) that lack Cyp26a1 differentiate poorly when compared to wild-type (wt) embryonic stem cells, even though the Cyp26a1 null ESCs contain much higher intracellular RA levels and express higher levels of one of the early, RAR-primary target genes, Hoxa1 [ 43 , 44 ].…”

Section: Introduction To Retinoids Vitamin a And Retinoic Acid Receptorsmentioning

confidence: 99%

Retinoids in the Pathogenesis and Treatment of Liver Diseases

et al. 2022

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Vitamin A (VA), all-trans-retinol (ROL), and its analogs are collectively called retinoids. Acting through the retinoic acid receptors RARα, RARβ, and RARγ, all-trans-retinoic acid, an active metabolite of VA, is a potent regulator of numerous biological pathways, including embryonic and somatic cellular differentiation, immune functions, and energy metabolism. The liver is the primary organ for retinoid storage and metabolism in humans. For reasons that remain incompletely understood, a body of evidence shows that reductions in liver retinoids, aberrant retinoid metabolism, and reductions in RAR signaling are implicated in numerous diseases of the liver, including hepatocellular carcinoma, non-alcohol-associated fatty liver diseases, and alcohol-associated liver diseases. Conversely, restoration of retinoid signaling, pharmacological treatments with natural and synthetic retinoids, and newer agonists for specific RARs show promising benefits for treatment of a number of these liver diseases. Here we provide a comprehensive review of the literature demonstrating a role for retinoids in limiting the pathogenesis of these diseases and in the treatment of liver diseases.

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Section: Introduction To Retinoids Vitamin a And Retinoic Acid Receptorsmentioning

confidence: 99%

Retinoids in the Pathogenesis and Treatment of Liver Diseases

et al. 2022

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“…While the key roles of reactive oxygen species (ROS) or hypoxia in HSC fate have been studied in detail (Suda et al , 2011), the interplay between metabolism and epigenetic HSC regulation is comparatively less explored. A recent study has identified retinoic acid and its metabolite 4‐oxo‐retinoic acid as master regulators of metabolic hubs involved in epigenetic regulation of transcriptional networks controlling HSC fate (Schönberger et al , 2022). All in all, an important conclusion of these studies is that the balance between HSC self‐renewal and differentiation cannot be thought of as a simple binary switch.…”

Section: Figure Model Of Metabolic and Epigenetic Crosstalk During Re...mentioning

confidence: 99%

Stem cells “aclymatise” to regenerate the blood system

Lisi‐Vega

Méndez‐Ferrer

2022

The EMBO Journal

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How blood stem cells balance fate decisions between quiescence maintenance and differentiation during recovery from cancer treatment remains poorly understood. A recent study by Umemoto et al (2022) uncovers an unexpected linkage between metabolic and epigenetic regulation of haematopoiesis, suggesting new targets in haematopoietic regeneration, with possible implications in leukaemogenesis and therapy resistance.

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“…One protocol covers signaling lipids and retinoids, while the second detects tricarboxylic acid cycle metabolites and amino acids. For complete details on the use and execution of this protocol, please refer to Schönberger et al. (2022) .…”

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confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to Schönberger et al. (2022) .…”

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confidence: 99%