Characterization of age-related gene expression profiling in bone marrow and epididymal adipocytes

Liu, Lifen; Shen, Wen-Jun; Ueno, Masaki; Patel, Shushma; Kraemer, Fredric B.

doi:10.1186/1471-2164-12-212

Cited by 126 publications

(148 citation statements)

References 55 publications

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“…While neurotropin levels were not higher in WAT, expression was significantly lower in BAT in hibernating ground squirrels. The increase in bone marrow adipose could originate from differentiation of mesenchymal stromal cells into adipocytes instead of osteoblasts through adipogenesis (47). In humans and other nonhibernating mammals (82), bone marrow adipose increases with age and is not seasonally reversed as seen in the ground squirrel bone marrow sections in this study.…”

Section: Discussionmentioning

confidence: 53%

“…The accumulation of adipocytes could be for energy storage during hibernation or be negative regulators of hematopoiesis (62) and osteoblast activity (42). Bone marrow adipocytes in mice show differential gene expression compared with epididymal adipocytes (47,82). In examination of the 14 genes reported to increase in mouse bone marrow adipose, only one was higher during hibernation in squirrels (oncostatin M) with the remainder showing no change or decreasing during hibernation.…”

Section: Discussionmentioning

confidence: 99%

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Effects of hibernation on bone marrow transcriptome in thirteen-lined ground squirrels

Cooper

Sell

Fahrenkrog

et al. 2016

Physiological Genomics

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M. Effects of hibernation on bone marrow transcriptome in thirteen-lined ground squirrels. Physiol Genomics 48: 513-525, 2016. First published May 20, 2016 doi:10.1152/physiolgenomics.00120.2015.-Mammalian hibernators adapt to prolonged periods of immobility, hypometabolism, hypothermia, and oxidative stress, each capable of reducing bone marrow activity. In this study bone marrow transcriptomes were compared among thirteen-lined ground squirrels collected in July, winter torpor, and winter interbout arousal (IBA). The results were consistent with a suppression of acquired immune responses, and a shift to innate immune responses during hibernation through higher complement expression. Consistent with the increase in adipocytes found in bone marrow of hibernators, expression of genes associated with white adipose tissue are higher during hibernation. Genes that should strengthen the bone by increasing extracellular matrix were higher during hibernation, especially the collagen genes. Finally, expression of heat shock proteins were lower, and cold-response genes were higher, during hibernation. No differential expression of hematopoietic genes involved in erythrocyte or megakaryocyte production was observed. This global view of the changes in the bone marrow transcriptome over both short term (torpor vs. IBA) and long term (torpor vs. July) hypothermia can explain several observations made about circulating blood cells and the structure and strength of the bone during hibernation. erythrocyte; leukocyte; megakaryocyte; osteoblast; adipose BONE MARROW IS A COMPLEX ORGAN consisting of many different cell types and stem cell pools. These cells express both unique and common sets of genes and likely influence each other's activities. Hematopoietic stem cells can differentiate into lymphoid progenitor cells that produce natural killer cells and lymphocytes, or into myeloid progenitor cells that give rise to erythrocytes, the remaining leukocytes, and megakaryocytes. Megakaryocytes in turn shed anucleated platelets involved in blood clotting and inflammation. Bone marrow resident mesenchymal stem cells can differentiate to produce resident bone cells including osteoblasts, adipocytes, and chondrocytes (64). Osteoblasts can terminally differentiate into osteocytes and are involved in maintaining bone strength and extracellular matrix production. Bone marrow adipose composition is affected by age, diet, and disease states. Bone marrow may also contain skeletal muscle and hepatocyte stem cell pools. Because of the rapid rate of mitosis by multiple resident stem cell pools, bone marrow is sensitive to damage by radiation and chemotherapy, leaving patients immunocompromised and anemic (25). Bone mineral density and collagen are decreased by prolonged disuse such as bed rest or immobilization (45,86). Recent studies have also demonstrated an increase in neutrophils, natural killer cells, and lymphocytes and a decrease in monocytes in patients subjected to 60 days of bed rest (38). Finally, bone marrow adipocytes increase in ...

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Effects of hibernation on bone marrow transcriptome in thirteen-lined ground squirrels

Cooper

Sell

Fahrenkrog

et al. 2016

Physiological Genomics

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“…This is particularly intriguing since rMAT is defined, in part, by its increased lipid saturation relative to cMAT [5]. Regarding dysfunction, gene expression in isolated B6 mouse MAT adipocytes suggests potential for mitochondrial dysfunction and altered fatty acid synthesis with aging [82]. Similar analyses in whole tibiae from B6 mice reveal age-related decreases in BAT-marker genes Prdm16 , FoxC2 , Adrb3 , and Dio2 that may also indicate a shift in the nature of the MAT adipocyte [47].…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

“…This is based on gene expression in whole tibia bones showing that BAT markers Prdm16 , Dio2 , FoxC2 and Pgc1α (but not Ucp1 ) are highly elevated relative to epididymal WAT (eWAT) and expressed at comparable levels to whole BAT - when normalized to the reference gene Fabp4 / aP2 [47]. In a separate study, Fabp4 was expressed at only 2.4-4.3% of what is observed in eWAT [82]. Thus, its use as a normalization tool in a complex tissue such as the tibia may significantly elevate predicted gene expression.…”

Section: Figurementioning

confidence: 99%

Marrow Adipose Tissue: Trimming the Fat

Scheller

Cawthorn

Burr

et al. 2016

Trends in Endocrinology & Metabolism

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165

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Marrow adipose tissue (MAT) is a unique fat depot, located in the skeleton, that has the potential to contribute to both local and systemic metabolic processes. In this review we highlight several recent conceptual developments pertaining to the origin and function of MAT adipocytes; consider the relationship of MAT to beige, brown, and white adipose depots; explore MAT expansion and turnover in humans and rodents; and discuss future directions for MAT research in the context of endocrine function and metabolic disease. MAT has the potential to exert both local and systemic effects on metabolic homeostasis, skeletal remodeling, hematopoiesis, and development of bone metastases. The diversity of these functions highlights the breadth of MAT’s potential impact on health and disease.

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“…The vascular niche may also play a role, and we identified a trend for increased interstitial edema and fibrohistiocytic proliferation in the short term (day 21) in RIC patients, suggesting that evaluation of vascular factors should be a potential consideration. Older age is an independent factor associated with increasing bone marrow adiposity and reduced hematopoietic cellularity [23,33]. RIC HCT is used for older patients or those with significant co-morbidities and thus we attempted to minimize this confounding factor by studying patients between the ages of 45-55.…”

Section: Discussionmentioning

confidence: 99%

Marrow damage and hematopoietic recovery following allogeneic bone marrow transplantation for acute leukemias: Effect of radiation dose and conditioning regimen

Wilke

Holtan

Sharkey

et al. 2016

Radiotherapy and Oncology

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Background and Purpose Total body irradiation (TBI) is a common component of hematopoietic cell transplantation (HCT) conditioning regimens. Preclinical studies suggest prolonged bone marrow (BM) injury after TBI could contribute to impaired engraftment and poor hematopoietic function. Materials and Methods We studied the longitudinal changes in the marrow environment in patients receiving allogeneic HCT with myeloablative (MA, n=42) and reduced intensity (RIC, n=56) doses of TBI from 2003-2013, including BM cellularity, histologic features of injury and repair, hematologic and immunologic recovery. Results Following MA conditioning, a 30% decrease in the marrow cellularity persisted at 1 year post-transplant (p=0.03). RIC HCT marrow cellularity transiently decreased but returned to baseline by 6 months even though the RIC group received mostly umbilical cord blood (UCB) grafts (82%, vs. 17% in the MA cohort, p<0.01). There was no evidence of persistent marrow vascular damage or inflammation. Recipients of more intensive conditioning did not show more persistent cytopenias with the exception of a tendency for minimal thrombocytopenia. Immune recovery was similar between MA and RIC. Conclusions These findings suggest that TBI associated with MA conditioning leads to prolonged reductions in marrow cellularity, but does not show additional histological evidence of long-term injury, which is further supported by similar peripheral counts and immunologic recovery.

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Characterization of age-related gene expression profiling in bone marrow and epididymal adipocytes

Cited by 126 publications

References 55 publications

Effects of hibernation on bone marrow transcriptome in thirteen-lined ground squirrels

Effects of hibernation on bone marrow transcriptome in thirteen-lined ground squirrels

Marrow Adipose Tissue: Trimming the Fat

Marrow damage and hematopoietic recovery following allogeneic bone marrow transplantation for acute leukemias: Effect of radiation dose and conditioning regimen

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