yuwei jiang - Academia.edu (original) (raw)

Papers by yuwei jiang

Bioscience Reports, 2020

Adipose tissue, the storage of excessive energy in the body, secretes various proteins called adi... more Adipose tissue, the storage of excessive energy in the body, secretes various proteins called adipokines, which connect the body’s nutritional status to the regulation of energy balance. Obesity triggers alterations of quantity and quality of various types of cells that reside in adipose tissue, including adipose stem cells (ASCs; referred to as adipose-derived stem/stromal cells in vitro). These alterations in the functionalities and properties of ASCs impair adipose tissue remodeling and adipose tissue function, which induces low-grade systemic inflammation, progressive insulin resistance, and other metabolic disorders. In contrast, the ability of ASCs to recruit new adipocytes when faced with caloric excess leads to healthy adipose tissue expansion, associated with lower amounts of inflammation, fibrosis, and insulin resistance. This review focuses on recent advances in our understanding of the identity of ASCs and their roles in adipose tissue development, homeostasis, expansion...

SummaryBeneficial effects of resistance exercise on metabolic health and particularly muscle hype... more SummaryBeneficial effects of resistance exercise on metabolic health and particularly muscle hypertrophy and fat loss are well established, but the underlying chemical and physiological mechanisms are not fully understood. Here we identified a myometabolite-mediated metabolic pathway that is essential for the beneficial metabolic effects of resistance exercisein vivo. We showed that substantial accumulation of the tricarboxylic acid cycle intermediate α-ketoglutaric acid (AKG) is a metabolic signature of resistance exercise performance. Interestingly, human plasma AKG level is also negatively correlated with BMI. Pharmacological elevation of circulating AKG induces muscle hypertrophy, brown adipose tissue (BAT) thermogenesis, and white adipose tissue (WAT) lipolysisin vivo. We further found that AKG stimulates the adrenal release of adrenaline through 2-oxoglutarate receptor 1 (OXGR1) expressed in adrenal glands. Finally, by using both loss-of-function and gain-of-function mouse mod...

Genes & Development, 2019

Fat storage in adult mammals is a highly regulated process that involves the mobilization of adip... more Fat storage in adult mammals is a highly regulated process that involves the mobilization of adipocyte progenitor cells (APCs) that differentiate to produce new adipocytes. Here we report a role for the broadly conserved miR-26 family of microRNAs (miR-26a-1, miR-26a-2, and miR-26b) as major regulators of APC differentiation and adipose tissue mass. Deletion of all miR-26-encoding loci in mice resulted in a dramatic expansion of adipose tissue in adult animals fed normal chow. Conversely, transgenic overexpression of miR-26a protected mice from high-fat diet-induced obesity. These effects were attributable to a cell-autonomous function of miR-26 as a potent inhibitor of APC differentiation. miR-26 blocks adipogenesis, at least in part, by repressing expression of Fbxl19, a conserved miR-26 target without a previously known role in adipocyte biology that encodes a component of SCF-type E3 ubiquitin ligase complexes. These findings have therefore revealed a novel pathway that plays a ...

Cell reports, Jan 6, 2014

Adipose tissues have striking plasticity, highlighted by childhood and adult obesity. Using adipo... more Adipose tissues have striking plasticity, highlighted by childhood and adult obesity. Using adipose lineage analyses, smooth muscle actin (SMA)-mural cell-fate mapping, and conditional PPARγ deletion to block adipocyte differentiation, we find two phases of adipocyte generation that emanate from two independent adipose progenitor compartments: developmental and adult. These two compartments are sequentially required for organ formation and maintenance. Although both developmental and adult progenitors are specified during the developmental period and express PPARγ, they have distinct microanatomical, functional, morphogenetic, and molecular profiles. Furthermore, the two compartments derive from different lineages; whereas adult adipose progenitors fate-map from an SMA+ mural lineage, developmental progenitors do not. Remarkably, the adult progenitor compartment appears to be specified earlier than the developmental cells and then enters the already developmentally formed adipose de...

Developmental Biology, 2013

optix, the Drosophila ortholog of the SIX3/6 gene family in vertebrate, encodes a homeodomain pro... more optix, the Drosophila ortholog of the SIX3/6 gene family in vertebrate, encodes a homeodomain protein with a SIX protein-protein interaction domain. In vertebrates, Six3/6 genes are required for normal eye as well as brain development. However, the normal function of optix in Drosophila remains unknown due to lack of loss-of-function mutation. Previous studies suggest that optix is likely to play an important role as part of the retinal determination (RD) network. To elucidate normal optix function during retinal development, multiple null alleles for optix have been generated. Loss-of-function mutations in optix result in lethality at the pupae stage. Surprisingly, close examination of its function during eye development reveals that, unlike other members of the RD network, optix is required only for morphogenetic furrow (MF) progression, but not initiation. The mechanisms by which optix regulates MF progression is likely through regulation of signaling molecules in the furrow. Specifically, although unaffected during MF initiation, expression of dpp in the MF is dramatically reduced in optix mutant clones. In parallel, we find that optix is regulated by sine oculis and eyes absent, key members of the RD network. Furthermore, positive feedback between optix and sine oculis and eyes absent is observed, which is likely mediated through dpp signaling pathway. Together with the observation that optix expression does not depend on hh or dpp, we propose that optix functions together with hh to regulate dpp in the MF, serving as a link between the RD network and the patterning pathways controlling normal retinal development.

Cell metabolism, Jan 21, 2016

Cold temperatures induce progenitor cells within white adipose tissue to form beige adipocytes th... more Cold temperatures induce progenitor cells within white adipose tissue to form beige adipocytes that burn energy and generate heat; this is a potential anti-diabesity therapy. However, the potential to form cold-induced beige adipocytes declines with age. This creates a clinical roadblock to potential therapeutic use in older individuals, who constitute a large percentage of the obesity epidemic. Here we show that aging murine and human beige progenitor cells display a cellular aging, senescence-like phenotype that accounts for their age-dependent failure. Activating the senescence pathway, either genetically or pharmacologically, in young beige progenitors induces premature cellular senescence and blocks their potential to form cold-induced beige adipocytes. Conversely, genetically or pharmacologically reversing cellular aging by targeting the p38/MAPK-p16(Ink4a) pathway in aged mouse or human beige progenitor cells rejuvenates cold-induced beiging. This in turn increases glucose se...

eLife, 2020

Adipocytes arise from distinct progenitor populations during developmental and adult stages but l... more Adipocytes arise from distinct progenitor populations during developmental and adult stages but little is known about how developmental progenitors differ from adult progenitors. Here, we investigate the role of platelet-derived growth factor receptor alpha (PDGFRα) in the divergent regulation of the two different adipose progenitor cells (APCs). Using in vivo adipose lineage tracking and deletion mouse models, we found that developmental PDGFRα+ cells are adipogenic and differentiated into mature adipocytes, and the deletion of Pdgfra in developmental adipose lineage disrupted white adipose tissue (WAT) formation. Interestingly, adult PDGFRα+ cells do not significantly contribute to adult adipogenesis, and deleting Pdgfra in adult adipose lineage did not affect WAT homeostasis. Mechanistically, embryonic APCs require PDGFRα for fate maintenance, and without PDGFRα, they underwent fate change from adipogenic to fibrotic lineage. Collectively, our findings indicate that PDGFRα+ cells...

Nature communications, Jan 26, 2017

Adipose progenitor cells (APCs) reside in a vascular niche, located within the perivascular compa... more Adipose progenitor cells (APCs) reside in a vascular niche, located within the perivascular compartment of adipose tissue blood vessels. Yet, the signals and mechanisms that govern adipose vascular niche formation and APC niche interaction are unknown. Here we show that the assembly and maintenance of the adipose vascular niche is controlled by PPARγ acting within APCs. PPARγ triggers a molecular hierarchy that induces vascular sprouting, APC vessel niche affinity and APC vessel occupancy. Mechanistically, PPARγ transcriptionally activates PDGFRβ and VEGF. APC expression and activation of PDGFRβ promotes the recruitment and retention of APCs to the niche. Pharmacologically, targeting PDGFRβ disrupts APC niche contact thus blocking adipose tissue expansion. Moreover, enhanced APC expression of VEGF stimulates endothelial cell proliferation and expands the adipose niche. Consequently, APC niche communication and retention are boosted by VEGF thereby impairing adipogenesis. Our data in...

Nature Communications, 2016

Cold temperatures induce formation of beige adipocytes, which convert glucose and fatty acids to ... more Cold temperatures induce formation of beige adipocytes, which convert glucose and fatty acids to heat, and may increase energy expenditure, reduce adiposity and lower blood glucose. This therapeutic potential is unrealized, hindered by a dearth of genetic tools to fate map, track and manipulate beige progenitors and 'beiging'. Here we examined 12 Cre/inducible Cre mouse strains that mark adipocyte, muscle and mural lineages, three proposed beige origins. Among these mouse strains, only those that marked perivascular mural cells tracked the cold-induced beige lineage. Two SMA-based strains, SMA-Cre ERT2 and SMA-rtTA, fate mapped into the majority of cold-induced beige adipocytes and SMA-marked progenitors appeared essential for beiging. Disruption of the potential of the SMA-tracked progenitors to form beige adipocytes was accompanied by an inability to maintain body temperature and by hyperglycaemia. Thus, SMA-engineered mice may be useful to track and manipulate beige progenitors, beige adipocyte formation and function.

PLoS Genetics, 2013

Organ development is directed by selector gene networks. Eye development in the fruit fly Drosoph... more Organ development is directed by selector gene networks. Eye development in the fruit fly Drosophila melanogaster is driven by the highly conserved selector gene network referred to as the ''retinal determination gene network,'' composed of approximately 20 factors, whose core comprises twin of eyeless (toy), eyeless (ey), sine oculis (so), dachshund (dac), and eyes absent (eya). These genes encode transcriptional regulators that are each necessary for normal eye development, and sufficient to direct ectopic eye development when misexpressed. While it is well documented that the downstream genes so, eya, and dac are necessary not only during early growth and determination stages but also during the differentiation phase of retinal development, it remains unknown how the retinal determination gene network terminates its functions in determination and begins to promote differentiation. Here, we identify a switch in the regulation of ey by the downstream retinal determination genes, which is essential for the transition from determination to differentiation. We found that central to the transition is a switch from positive regulation of ey transcription to negative regulation and that both types of regulation require so. Our results suggest a model in which the retinal determination gene network is rewired to end the growth and determination stage of eye development and trigger terminal differentiation. We conclude that changes in the regulatory relationships among members of the retinal determination gene network are a driving force for key transitions in retinal development.

Cell, 2012

Adipose stem cells, which reside in a vascular niche, are essential to the development and mainte... more Adipose stem cells, which reside in a vascular niche, are essential to the development and maintenance of adipose tissue. Data from humans and rodents show that maintenance of adult adipose tissue is a dynamic process. Adipocyte turnover in young adult mice is estimated to be greater than 10% per month. The adipose stem cell niche is just as active, generating new adipocytes and replenishing the niche. This cycle occurs throughout life and responds to myriad environmental stimuli, including diet, pharmacological agents, and tissue injury. Adipose tissue deficiency (lipodystrophy) or excess (obesity) cause disease and serious secondary conditions, including diabetes, hypertension, hyperlipidemia, and even cancer. It is therefore critical to understand the life cycle of adipose tissue and how it is regulated. In this SnapShot, we integrate a variety of studies-cell culture, animal model, human retrospective, and clinical trials-to summarize what is currently known about the molecular basis of adipose tissue formation, its stem cell niche, and the pathogenesis of obesity. Adipocyte Formation and Expansion: Key Events and Molecules Adipose depot and adipocyte formation are multistep processes, involving stem cell commitment, quiescence, and proliferation, as well as early (recruitment) and late (lipid filling) differentiation. These highly orchestrated processes involve many cell types in adipose tissue, including mature adipocytes and stromal-vascular cells (SVCs). The SVCs include fibroblasts, smooth muscle cells, pericytes, endothelial cells, and adipogenic stem/progenitor cells. The perivascular location of the stem cells places them in an appropriate position to help coordinate these interactions as well as respond to blood-borne signals, such as nutrients and drugs. Adipose Stem Cell Proliferation Stem cells are poised in a delicate balance between quiescence and division. Cell division may create additional stem cells or cells that are destined to differentiate. To maintain the appropriate balance of stem cells and various progeny, decisions are tightly regulated by an assortment of inhibitory and stimulatory factors, which can be subdivided into at least three groups (1): cell-cycle regulators (e.g., p21, Cyclin D1, Rb, and E2Fs), hormones (e.g., thyroid and growth hormones), and angiogenic factors (e.g., VEGF and HGF). Significant progress has been made toward identifying the origin, location, and niche of adipose stem cells, as well as their molecular signature. The expression of PPARγ marks the adipose stem compartment. Lineage-tracing studies based on the expression of PPARγ indicate a perivascular location of adipose stem cells and highlight the vasculature as a critical stem cell niche (Tang et al., 2008). Stem cells reside in this niche as mural cells (those which physically surround the endothelial cells to provide structural support to blood vessels and are essential for normal vascular development). These PPARγ-positive mural cells fulfill the standard stem criteria: they are quiescent cells that retain label, and they proliferate and lineage trace into adipocytes. Recent data indicate that a subset of the stem cell compartment may derive from endothelial cells, which are proposed to undergo an epithelial to mesenchymal transition, thus changing fate from endothelial to mural (