Transplantation of mature adipocyte-derived dedifferentiated fat cells promotes locomotor functional recovery by remyelination and glial scar reduction after spinal cord injury in mice

Yamada, Hiromi; Ito, Daisuke; Oki, Yoshinao; Kitagawa, Masato; Matsumoto, Tarô; Watari, Tosihiro; Kano, Koichiro

doi:10.1016/j.bbrc.2014.10.082

Cited by 15 publications

(6 citation statements)

References 20 publications

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“…In general, the phenomenon is manifested by a change in the shape, gene expression pattern, protein expression pattern, and function (Yao & Wang, 2020). The process of dedifferentiation has been described in various cell types, including chondrocytes (Bianchi et al, 2019), adipocytes (Yamada et al, 2014), cardiomyocytes (Porrello et al, 2013), and Schwann cells (Carr & Johnston, 2017; Norrmén et al, 2018). Regarding the CNS, recent studies suggested that astrocytes can dedifferentiate upon injury and may re‐acquire neural stem cell potential (Buffo et al, 2008; Gabel et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Transmembrane protein 119 is neither a specific nor a reliable marker for microglia

Vankriekelsvenne

Chrzanowski

Manzhula

et al. 2022

Glia

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Microglia are the resident innate immune cells of the central nervous system (CNS) parenchyma. To determine the impact of microglia on disease development and progression in neurodegenerative and neuroinflammatory diseases, it is essential to distinguish microglia from peripheral macrophages/monocytes, which are eventually equally recruited. It has been suggested that transmembrane protein 119 (TMEM119) serves as a reliable microglia marker that discriminates resident microglia from blood‐derived macrophages in the human and murine brain. Here, we investigated the validity of TMEM119 as a microglia marker in four in vivo models (cuprizone intoxication, experimental autoimmune encephalomyelitis (EAE), permanent filament middle cerebral artery occlusion (fMCAo), and intracerebral 6‐hydroxydopamine (6‐OHDA) injections) as well as post mortem multiple sclerosis (MS) brain tissues. In all applied animal models and post mortem MS tissues, we found increased densities of ionized calcium‐binding adapter molecule 1+ (IBA1+) cells, paralleled by a significant decrease in TMEM119 expression. In addition, other cell types in peripheral tissues (i.e., follicular dendritic cells and brown adipose tissue) were also found to express TMEM119. In summary, this study demonstrates that TMEM119 is not exclusively expressed by microglia nor does it label all microglia, especially under cellular stress conditions. Since novel transgenic lines have been developed to label microglia using the TMEM119 promotor, downregulation of TMEM119 expression might interfere with the results and should, thus, be considered when working with these transgenic mouse models.

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Section: Discussionmentioning

confidence: 99%

Transmembrane protein 119 is neither a specific nor a reliable marker for microglia

Vankriekelsvenne

Chrzanowski

Manzhula

et al. 2022

Glia

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“…Dedifferentiation of cells is a reversal of the developmental process, such as in cases of differentiated mature cells with specialized functions that produce undifferentiated progenitor cells [1][2][3] or they undergo a self-repair mechanism [4,5] under certain physiological and/or pathological conditions. Spalding et al reported that approximately 10% of adipocytes in human white adipose tissue are renewed annually during adult age [1].…”

Section: Introductionmentioning

confidence: 99%

Insulin negatively regulates dedifferentiation of mouse adipocytes in vitro

et al. 2020

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Insulin plays an important role during adipogenic differentiation of animal preadipocytes and the maintenance of mature phenotypes. However, its role and mechanism in dedifferentiation of adipocyte remains unclear. This study investigated the effects of insulin on dedifferentiation of mice adipocytes, and the potential mechanisms. The preadipocytes were isolated from the subcutaneous white adipose tissue of wild type (WT), TNFα gene mutant (TNFα-/-), leptin gene spontaneous point mutant (db/db) and TNFα-/-/db/db mice and were then induced for differentiation. Interestingly, dedifferentiation of these adipocytes occurred once removing exogenous insulin from the adipogenic medium. As characteristics of dedifferentiation of the adipocytes, downregulation of adipogenic markers, upregulation of stemness markers and loss of intracellular lipids were observed from the four genotypes. Notably, dedifferentiation was occurring earlier if the insulin signal was blocked. These dedifferentiated cells regained the potentials of the stem cell-like characteristics. There is no significant difference in the characteristics of the dedifferentiation between the adipocytes. Overall, the study provided evidence that insulin plays a negative regulatory role in the dedifferentiation of adipocytes. We also confirmed that both dedifferentiation of mouse adipocytes, and effect of the insulin on this process were independent of the cell genotypes, while it is a widespread phenomenon in the adipocytes.

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“…This newly established cell line, called dedifferentiated fat (DFAT) cells, then exhibits characteristics comparable to those of adipose‐derived stem cells (ASCs), found in the stromal vascular fraction of adipose tissue (Matsumoto et al., 2008). DFAT cells exhibit adipogenic, osteogenic, chondrogenic, cardiomyogenic, angiogenic, myogenic and neurogenic potentials under proper conditions both in vitro and in vivo (Kazama et al., 2008; Matsumoto et al., 2008; Nobusue et al., 2008; Oki et al., 2008; Yamada et al., 2014). Thus, compared to ASCs, DFAT cells have unique advantages in terms of their abundance, ease of isolation and homogeneity.…”

Section: Introductionmentioning

confidence: 99%

Generation of metabolically functional hepatocyte‐like cells from dedifferentiated fat cells by Foxa2, Hnf4a and Sall1 transduction

et al. 2020

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Transplantation of mature adipocyte-derived dedifferentiated fat cells promotes locomotor functional recovery by remyelination and glial scar reduction after spinal cord injury in mice

Cited by 15 publications

References 20 publications

Transmembrane protein 119 is neither a specific nor a reliable marker for microglia

Transmembrane protein 119 is neither a specific nor a reliable marker for microglia

Insulin negatively regulates dedifferentiation of mouse adipocytes in vitro

Generation of metabolically functional hepatocyte‐like cells from dedifferentiated fat cells by Foxa2, Hnf4a and Sall1 transduction

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