141 5 General Discussion clustering, I identified two groups: cluster 1, consisted of macrophages from the pancreas, lung, kidney, ovary, liver, and testis and derived from peripheral blood mononuclear cells (PBMC) as being more similar than macrophages from the other 13 tissues that were analyzed, belonging to cluster 2. The tissues belonging to cluster 1 are characterized by a high expression of genes involved in the electron transport chain, the TCA cycle, as well as in fatty acid oxidation. Even though we could group the tissues based on similarities, it is clear that the expression of metabolic genes greatly differs among different types of tissue-resident macrophages, even within one cluster. Therefore, their metabolic state appears to be very tissue-specific. Macrophages in cluster 1 all derive from fetal liver monocytes [10] except for PBMC. However, it is difficult to find commonalities for all the tissues belonging to this cluster. The liver and the pancreas have common endocrine and digestive functions. Both the liver and pancreas play a role in the regulation of blood sugar levels. In fact, the pancreas produces insulin and glucagon, which help to regulate blood sugar levels, while the liver stores glucose and converts it to glycogen, which can be released as needed to maintain blood sugar levels. The liver produces bile, which helps to break down fats in the small intestine, while the pancreas produces enzymes that help to break down carbohydrates, proteins, and fats. Other organs that are part of the cluster play a key role in detoxification, are the kidneys, as they help to remove waste products and excess fluid from the body. The lungs also have a detoxifying function as they help remove waste gases such as carbon dioxide from the body. Moreover, tissues can communicate through circulating proteins, like cytokines and hormones, in order to maintain tissue and organ homeostasis. The levels of these signaling molecules change according to an individual’s metabolic status which is altered under pathological conditions, altering therefore also the metabolic status of tissue-resident macrophages [11]. Even though I acknowledge that organs are much more than their tissue-resident macrophages, I hypothesized that macrophages from organs with similar functions might have commonalities in terms of their metabolism, as evidence pointed out that tissue-associated signature transcription factors also regulate metabolism [12,13]. However, although similarities can be found between some of these organs, there is something about the specific tissue niche that is important for macrophage metabolism that we still do not understand.
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