Adipose tissue at single-cell resolution.

Adipose tissue exhibits remarkable plasticity with capacity to change in size and cellular composition under physiological and pathophysiological conditions. The emergence of single-cell transcriptomics has rapidly transformed our understanding of the diverse array of cell types and cell states residing in adipose tissues and has provided insight into how transcriptional changes in individual cell types contribute to tissue plasticity. Here, we present a comprehensive overview of the cellular atlas of adipose tissues focusing on the biological insight gained from single-cell and single-nuclei transcriptomics of murine and human adipose tissues. We also offer our perspective on the exciting opportunities for mapping cellular transitions and crosstalk, which have been made possible by single-cell technologies.

Cellular mechanisms underlying adult tissue plasticity in Drosophila.

Adult tissues in Metazoa dynamically remodel their structures in response to environmental challenges including sudden injury, pathogen infection, and nutritional fluctuation, while maintaining quiescence under homoeostatic conditions. This characteristic, hereafter referred to as adult tissue plasticity, can prevent tissue dysfunction and improve the fitness of organisms in continuous and/or severe change of environments. With its relatively simple tissue structures and genetic tools, studies using the fruit fly Drosophila melanogaster have provided insights into molecular mechanisms that control cellular responses, particularly during regeneration and nutrient adaptation. In this review, we present the current understanding of cellular mechanisms, stem cell proliferation, polyploidization, and cell fate plasticity, all of which enable adult tissue plasticity in various Drosophila adult organs including the midgut, the brain, and the gonad, and discuss the organismal strategy in response to environmental changes and future directions of the research.

A Physiological behavior and tolerance of Lactuca sativa to lead nitrate and silver nitrate heavy metals / Comportamento fisiológico e tolerância de Lactuca sativa aos metais pesados nitrato de chumbo e nitrato de prata

This study goal to evaluate the effects of different concentrations of lead (Pb) and silver (Ag) on germination, initial growth and anatomical alterations of Lactuca sativa L. Plants use various mechanisms to reduce the impacts caused by anthropic action, such as xenobiotic elements of soils and water contaminated by heavy metals. These metals were supplied as lead nitrate and silver nitrate and the following treatments were established: control for both metals, maximum dose of heavy metals, for arable soils, allowed by the National Council of the Environment (Ag = 25 mg. Kg-¹, Pb = 180 mg. Kg-¹), double (Ag = 50 mg. Kg-¹, Pb = 360 mg. Kg-¹) and triple (Ag = 75 mg. Kg-¹, Pb = 540 mg. Kg-¹) of this dosage. Vigor and germination tests of the seeds and possible anatomical changes in the leaves and roots of lettuce plants were performed. The species showed a high capacity to germinate under Pb and Ag stress, and the germination was never completely inhibited; however, the germination decreased with increasing Pb concentrations, but not under Ag stress. The use of increasing doses of metals reduced seed vigor and increased chlorophyll content. An increase in biomass was also observed in plants from treatments submitted to Pb. The phytotoxic effects of metals were more pronounced at 15 days after sowing. Anatomically, L. sativa was influenced by metal concentrations, and had a reduction of up to 79.9% in root epidermis thickness at the highest Pb concentration, although some structures did not suffer significant changes. The results suggest that L. sativa presents tolerance to high concentrations of heavy metals, showing possible mechanisms to overcome the stress caused by these metals. In this research lettuce possibly used the mechanism of exclusion of metals retaining Pb and Ag in the roots preserving the photosynthetic apparatus in the aerial part of the plants. In general, the chemical element Pb was more toxic than Ag, in these experimental conditions.

Este estudo teve como objetivo avaliar os efeitos de diferentes concentrações de chumbo (Pb) e prata (Ag) na germinação, crescimento inicial e alterações anatômicas de Lactuca sativa L. As plantas utilizam vários mecanismos para reduzir os impactos causados pela ação antrópica, como elementos xenobióticos de solos e água contaminada por metais pesados. Esses metais foram fornecidos como nitrato de chumbo e nitrato de prata e foram estabelecidos os seguintes tratamentos:controle para ambos os metais, dose máxima de metais pesados, para solos cultiváveis, permitida pelo Conselho Nacional do Meio Ambiente (Ag = 25mg.Kg-¹, Pb = 180mg.Kg-¹), dobro (Ag = 50mg.Kg-¹, Pb = 360mg.Kg-¹) e triplo (Ag = 75mg.Kg-¹, Pb = 540 mg.Kg-¹) desta dosagem. Foram realizados testes de vigor e germinação das sementes e possíveis alterações anatômicas nas folhas e raízes das plantas de alface. A espécie apresentou alta capacidade de germinar sob estresse de Ag e Pb, e a germinação nunca foi completamente inibida; entretanto, a germinação diminuiu com o aumento das concentrações de Pb, mas não sob estresse de Ag. O uso de doses crescentes dos metais, reduziu o vigor das sementes e aumentou o teor de clorofila. Também foi observado aumento da biomassa nas plantas a partir dos tratamentos submetidos ao Pb. Os efeitos fitotóxicos dos metais foram mais acentuados aos 15 dias após a semeadura. Anatomicamente, L. sativa foi influenciada pelas concentrações de metais, e teve uma redução de até 79,9% na espessura da epiderme radicular na maior concentração de Pb, embora algumas estruturas não tenham sofrido alterações significativas. Os resultados sugerem que L. sativa apresenta tolerância a altas concentrações de metais pesados, mostrando possíveis mecanismos para superar o estresse causado por esses metais. Nesta pesquisa a alface possivelmente utilizou o mecanismo de exclusão de metais retendo Pb e Ag nas raízes preservando o aparato [...].

A Physiological behavior and tolerance of Lactuca sativa to lead nitrate and silver nitrate heavy metals

Abstract This study goal to evaluate the effects of different concentrations of lead (Pb) and silver (Ag) on germination, initial growth and anatomical alterations of Lactuca sativa L. Plants use various mechanisms to reduce the impacts caused by anthropic action, such as xenobiotic elements of soils and water contaminated by heavy metals. These metals were supplied as lead nitrate and silver nitrate and the following treatments were established: control for both metals, maximum dose of heavy metals, for arable soils, allowed by the National Council of the Environment (Ag = 25 mg. Kg-1, Pb = 180 mg. Kg-1), double (Ag = 50 mg. Kg-1, Pb = 360 mg. Kg-1) and triple (Ag = 75 mg. Kg-1, Pb = 540 mg. Kg -1) of this dosage. Vigor and germination tests of the seeds and possible anatomical changes in the leaves and roots of lettuce plants were performed. The species showed a high capacity to germinate under Pb and Ag stress, and the germination was never completely inhibited; however, the germination decreased with increasing Pb concentrations, but not under Ag stress. The use of increasing doses of metals reduced seed vigor and increased chlorophyll content. An increase in biomass was also observed in plants from treatments submitted to Pb. The phytotoxic effects of metals were more pronounced at 15 days after sowing. Anatomically, L. sativa was influenced by metal concentrations, and had a reduction of up to 79.9% in root epidermis thickness at the highest Pb concentration, although some structures did not suffer significant changes. The results suggest that L. sativa presents tolerance to high concentrations of heavy metals, showing possible mechanisms to overcome the stress caused by these metals. In this research lettuce possibly used the mechanism of exclusion of metals retaining Pb and Ag in the roots preserving the photosynthetic apparatus in the aerial part of the plants. In general, the chemical element Pb was more toxic than Ag, in these experimental conditions.

Resumo Este estudo teve como objetivo avaliar os efeitos de diferentes concentrações de chumbo (Pb) e prata (Ag) na germinação, crescimento inicial e alterações anatômicas de Lactuca sativa L. As plantas utilizam vários mecanismos para reduzir os impactos causados pela ação antrópica, como elementos xenobióticos de solos e água contaminada por metais pesados. Esses metais foram fornecidos como nitrato de chumbo e nitrato de prata e foram estabelecidos os seguintes tratamentos: controle para ambos os metais, dose máxima de metais pesados, para solos cultiváveis, permitida pelo Conselho Nacional do Meio Ambiente (Ag = 25 mg.Kg-1, Pb = 180 mg.Kg-1), dobro (Ag = 50 mg.Kg-1, Pb = 360 mg.Kg-1) e triplo (Ag = 75 mg.Kg-1, Pb = 540 mg.Kg -1) desta dosagem. Foram realizados testes de vigor e germinação das sementes e possíveis alterações anatômicas nas folhas e raízes das plantas de alface. A espécie apresentou alta capacidade de germinar sob estresse de Ag e Pb, e a germinação nunca foi completamente inibida; entretanto, a germinação diminuiu com o aumento das concentrações de Pb, mas não sob estresse de Ag. O uso de doses crescentes dos metais, reduziu o vigor das sementes e aumentou o teor de clorofila. Também foi observado aumento da biomassa nas plantas a partir dos tratamentos submetidos ao Pb. Os efeitos fitotóxicos dos metais foram mais acentuados aos 15 dias após a semeadura. Anatomicamente, L. sativa foi influenciada pelas concentrações de metais, e teve uma redução de até 79,9% na espessura da epiderme radicular na maior concentração de Pb, embora algumas estruturas não tenham sofrido alterações significativas. Os resultados sugerem que L. sativa apresenta tolerância a altas concentrações de metais pesados, mostrando possíveis mecanismos para superar o estresse causado por esses metais. Nesta pesquisa a alface possivelmente utilizou o mecanismo de exclusão de metais retendo Pb e Ag nas raízes preservando o aparato fotossintético na parte aérea das plantas. De forma geral o elemento químico Pb se mostrou mais tóxico que Ag, nestas condições experimentais.

A Physiological behavior and tolerance of Lactuca sativa to lead nitrate and silver nitrate heavy metals / Comportamento fisiológico e tolerância de Lactuca sativa aos metais pesados nitrato de chumbo e nitrato de prata

This study goal to evaluate the effects of different concentrations of lead (Pb) and silver (Ag) on germination, initial growth and anatomical alterations of Lactuca sativa L. Plants use various mechanisms to reduce the impacts caused by anthropic action, such as xenobiotic elements of soils and water contaminated by heavy metals. These metals were supplied as lead nitrate and silver nitrate and the following treatments were established: control for both metals, maximum dose of heavy metals, for arable soils, allowed by the National Council of the Environment (Ag = 25 mg. Kg-1, Pb = 180 mg. Kg-1), double (Ag = 50 mg. Kg-1, Pb = 360 mg. Kg-1) and triple (Ag = 75 mg. Kg-1, Pb = 540 mg. Kg -1) of this dosage. Vigor and germination tests of the seeds and possible anatomical changes in the leaves and roots of lettuce plants were performed. The species showed a high capacity to germinate under Pb and Ag stress, and the germination was never completely inhibited; however, the germination decreased with increasing Pb concentrations, but not under Ag stress. The use of increasing doses of metals reduced seed vigor and increased chlorophyll content. An increase in biomass was also observed in plants from treatments submitted to Pb. The phytotoxic effects of metals were more pronounced at 15 days after sowing. Anatomically, L. sativa was influenced by metal concentrations, and had a reduction of up to 79.9% in root epidermis thickness at the highest Pb concentration, although some structures did not suffer significant changes. The results suggest that L. sativa presents tolerance to high concentrations of heavy metals, showing possible mechanisms to overcome the stress caused by these metals. In this research lettuce possibly used the mechanism of exclusion of metals retaining Pb and Ag in the roots preserving the photosynthetic apparatus in the aerial part of the plants. In general, the chemical element Pb was more toxic than Ag, in these experimental conditions.

Este estudo teve como objetivo avaliar os efeitos de diferentes concentrações de chumbo (Pb) e prata (Ag) na germinação, crescimento inicial e alterações anatômicas de Lactuca sativa L. As plantas utilizam vários mecanismos para reduzir os impactos causados pela ação antrópica, como elementos xenobióticos de solos e água contaminada por metais pesados. Esses metais foram fornecidos como nitrato de chumbo e nitrato de prata e foram estabelecidos os seguintes tratamentos: controle para ambos os metais, dose máxima de metais pesados, para solos cultiváveis, permitida pelo Conselho Nacional do Meio Ambiente (Ag = 25mg.Kg-1, Pb = 180mg.Kg-1), dobro (Ag = 50mg.Kg-1, Pb = 360mg.Kg-1) e triplo (Ag = 75mg.Kg-1, Pb = 540 mg.Kg -1) desta dosagem. Foram realizados testes de vigor e germinação das sementes e possíveis alterações anatômicas nas folhas e raízes das plantas de alface. A espécie apresentou alta capacidade de germinar sob estresse de Ag e Pb, e a germinação nunca foi completamente inibida; entretanto, a germinação diminuiu com o aumento das concentrações de Pb, mas não sob estresse de Ag. O uso de doses crescentes dos metais, reduziu o vigor das sementes e aumentou o teor de clorofila. Também foi observado aumento da biomassa nas plantas a partir dos tratamentos submetidos ao Pb. Os efeitos fitotóxicos dos metais foram mais acentuados aos 15 dias após a semeadura. Anatomicamente, L. sativa foi influenciada pelas concentrações de metais, e teve uma redução de até 79,9% na espessura da epiderme radicular na maior concentração de Pb, embora algumas estruturas não tenham sofrido alterações significativas. Os resultados sugerem que L. sativa apresenta tolerância a altas concentrações de metais pesados, mostrando possíveis mecanismos para superar o estresse causado por esses metais. Nesta pesquisa a alface possivelmente utilizou o mecanismo de exclusão de metais retendo Pb e Ag nas raízes preservando o aparato fotossintético na parte aérea das plantas. De forma geral o elemento químico Pb se mostrou mais tóxico que Ag, nestas condições experimentais.

A New Procedure in Bone Engineering Using Induced Adipose Tissue.

Background: Osteoporosis is associated with a metabolic imbalance between adipogenesis and osteogenesis. We hypothesized that implanting a carrier for differentiated stem cells and signaling molecules inside adipose tissues could be used to enable transdifferentiation between cells, upregulate osteogenesis, and support bone formation, which may regain the balance between osteogenesis and adipogenesis. Methodology: A CL1 human mesenchymal stem cell line was grown in an osteogenic medium to differentiate into osteoblasts, and the differentiated cells were then exposed to an adipogenic medium to stimulate differentiation into adipocytes. Osteogenic and adipogenic differentiation were confirmed by the following assays: alkaline phosphatase staining, Nile red Staining, and quantitative real-time polymerase chain reaction (qPCR). The ratio of adipocytes to osteocytes for both cases was calculated. To evaluate bone induction in vivo, a calcium sulfate/hydroxyapatite cement was prepared in a syringe and then seeded with 106 cells/mL of rat bone marrow stromal cells (rMSCs) and covered with 1 mL of tissue culture media containing 0.1 mg of bone morphogenetic protein 7 (BMP-7). The construct was injected into the abdominal fat tissue of 10 male Sprague-Dawley rats. Results: The conversion of osteocytes to adipocytes was 20-fold greater than the reverse conversion, and the area of bone regeneration was 15.7 ± 3.7%, the area of adipose tissue was 65.8 ± 13.1%, and the area of fibrous tissue was 18.3 ± 7.8%. Conclusion: Adipogenic interconversion and associated bone formation demonstrate the potential of a new therapy for balancing osteogenesis and adipogenesis.

FGF15/19 is required for adipose tissue plasticity in response to thermogenic adaptations.

OBJECTIVE: To determine the role of enterokine FGF15/19 in adipose tissue thermogenic adaptations. METHODS: Circulating FGF19 and gene expression (qRT-PCR) levels were assessed in subcutaneous adipose tissue from obese human patients. Effects of experimentally increased FGF15 and FGF19 levels in vivo were determined in mice using adenoviral and adeno-associated vectors. Adipose tissues were characterized in FGF15-null mice under distinct cold-related thermogenic challenges. The analyses spanned metabolic profiling, tissue characterization, histology, gene expression, and immunoblot assays. RESULTS: In humans, FGF19 levels are directly associated with UCP1 gene expression in subcutaneous adipose tissue. Experimental increases in FGF15 or FGF19 induced white fat browning in mice as demonstrated by the appearance of multilocular beige cells and markers indicative of a beige phenotype, including increased UCP1 protein levels. Mice lacking FGF15 showed markedly impaired white adipose tissue browning and a mild reduction in parameters indicative of BAT activity in response to cold-induced environmental thermogenic challenges. This was concomitant with signs of altered systemic metabolism, such as reduced glucose tolerance and impaired cold-induced insulin sensitization. CONCLUSIONS: Enterokine FGF15/19 is a key factor required for adipose tissue plasticity in response to thermogenic adaptations.

Plasticity of Epididymal Adipose Tissue in Response to Diet-Induced Obesity at Single-Nucleus Resolution.

Adipose tissues display a remarkable ability to adapt to the dietary status. Here, we have applied single-nucleus RNA-seq to map the plasticity of mouse epididymal white adipose tissue at single-nucleus resolution in response to high-fat-diet-induced obesity. The single-nucleus approach allowed us to recover all major cell types and to reveal distinct transcriptional stages along the entire adipogenic trajectory from preadipocyte commitment to mature adipocytes. We demonstrate the existence of different adipocyte subpopulations and show that obesity leads to disappearance of the lipogenic subpopulation and increased abundance of the stressed lipid-scavenging subpopulation. Moreover, obesity is associated with major changes in the abundance and gene expression of other cell populations, including a dramatic increase in lipid-handling genes in macrophages at the expense of macrophage-specific genes. The data provide a powerful resource for future hypothesis-driven investigations of the mechanisms of adipocyte differentiation and adipose tissue plasticity.

Can a Peritoneal Conduit Become an Artery?

OBJECTIVE: Current vascular grafts all have limitations. This study examined peritoneum as a potential graft material and the in vivo transfer of peritoneum into a functional artery like conduit after end to end anastomosis into the common carotid artery of sheep. The aim was to investigate whether implantation of a peritoneal tube into the arterial tree results in a structure with function, histological findings, and gene expression like an artery, and whether such arterialisation occurs through a conversion of the phenotype of peritoneal cells or from host cell migration into the implant. METHODS: Peritoneum with adherent rectus aponeurosis from sheep was used to form tubular vascular grafts that were implanted into the common carotid artery of six sheep, then removed after five months. Two sheep received allogenic peritoneal grafts and four sheep received autologous peritoneal grafts. RESULTS: One sheep died shortly after implantation, so five of the six sheep were followed. Five months after implantation, four of the five remaining grafts were patent. Three of four patent grafts were aneurysmal. The four patent grafts had developed an endothelial layer indistinguishable from that of the adjacent normal artery, and a medial layer with smooth muscle cells with a surrounding adventitia. The new conduit displayed vasomotor function not present at the time of implantation. DNA genotyping showed that the media in the new conduit consisted of recipient smooth muscle cells. Little difference in mRNA expression was demonstrated between the post-implantation conduit and normal artery. CONCLUSION: During a five month implantation period in the arterial system, peritoneum converted into a tissue that histologically and functionally resembled a normal artery, with a functional genetic expression that resembled that of an artery. Single nucleotide polymorphism analysis indicated that this conversion occurs through host cell migration into the graft.

White and beige adipocytes: are they metabolically distinct?

The white adipose tissue (WAT) exhibits great plasticity and can undergo "browning" and acquire features of the brown adipose tissue (BAT), which takes place following cold exposure, chronic endurance exercise or ß3-adrenergic stimulation. WAT that underwent browning is characterized by the presence of "beige" adipocytes, which are morphologically similar to brown adipocytes, express uncoupling protein 1 (UCP1) and are considered thermogenically competent. Thus, inducing a BAT-like phenotype in the WAT could promote energy dissipation within this depot, reducing the availability of substrate that would otherwise be stored in the WAT. Importantly, BAT in humans only represents a small proportion of total body mass, which limits the thermogenic capacity of this tissue. Therefore, browning of the WAT could significantly expand the energy-dissipating capacity of the organism and be of therapeutic value in the treatment of metabolic diseases. However, the question remains as to whether WAT indeed changes its metabolic profile from an essentially fat storage/release compartment to an energy dissipating compartment that functions much like BAT. Here, we discuss the differences with respect to thermogenic capacity and metabolic characteristics between white and beige adipocytes to determine whether the latter cells indeed significantly enhance their capacity to dissipate energy through UCP1-mediated mitochondrial uncoupling or by the activation of alternative UCP1-independent futile cycles.

A model for one-dimensional morphoelasticity and its application to fibroblast-populated collagen lattices.

The mechanical behaviour of solid biological tissues has long been described using models based on classical continuum mechanics. However, the classical continuum theories of elasticity and viscoelasticity cannot easily capture the continual remodelling and associated structural changes in biological tissues. Furthermore, models drawn from plasticity theory are difficult to apply and interpret in this context, where there is no equivalent of a yield stress or flow rule. In this work, we describe a novel one-dimensional mathematical model of tissue remodelling based on the multiplicative decomposition of the deformation gradient. We express the mechanical effects of remodelling as an evolution equation for the effective strain, a measure of the difference between the current state and a hypothetical mechanically relaxed state of the tissue. This morphoelastic model combines the simplicity and interpretability of classical viscoelastic models with the versatility of plasticity theory. A novel feature of our model is that while most models describe growth as a continuous quantity, here we begin with discrete cells and develop a continuum representation of lattice remodelling based on an appropriate limit of the behaviour of discrete cells. To demonstrate the utility of our approach, we use this framework to capture qualitative aspects of the continual remodelling observed in fibroblast-populated collagen lattices, in particular its contraction and its subsequent sudden re-expansion when remodelling is interrupted.

A New Role for Browning as a Redox and Stress Adaptive Mechanism?

The worldwide epidemic of obesity and metabolic disorders is focusing the attention of the scientific community on white adipose tissue (WAT) and its biology. This tissue is characterized not only by its capability to change in size and shape but also by its heterogeneity and versatility. WAT can be converted into brown fat-like tissue according to different physiological and pathophysiological situations. The expression of uncoupling protein-1 in brown-like adipocytes changes their function from energy storage to energy dissipation. This plasticity, named browning, was recently rediscovered and convergent recent accounts, including in humans, have revived the idea of using these oxidative cells to fight against metabolic diseases. Furthermore, recent reports suggest that, beside the increased energy dissipation and thermogenesis that may have adverse effects in situations such as cancer-associated cachexia and massive burns, browning could be also considered as an adaptive stress response to high redox pressure and to major stress that could help to maintain tissue homeostasis and integrity. The aim of this review is to summarize the current knowledge concerning brown adipocytes and the browning process and also to explore unexpected putative role(s) for these cells. While it is important to find new browning inducers to limit energy stores and metabolic diseases, it also appears crucial to develop new browning inhibitors to limit adverse energy dissipation in wasting-associated syndromes.

Complement-triggered pathways orchestrate regenerative responses throughout phylogenesis.

Adult tissue plasticity, cell reprogramming, and organ regeneration are major challenges in the field of modern regenerative medicine. Devising strategies to increase the regenerative capacity of tissues holds great promise for dealing with donor organ shortages and low transplantation outcomes and also provides essential impetus to tissue bioengineering approaches for organ repair and replacement. The inherent ability of cells to reprogram their fate by switching into an embryonic-like, pluripotent progenitor state is an evolutionary vestige that in mammals has been retained mostly in fetal tissues and persists only in a few organs of the adult body. Tissue regeneration reflects the capacity of terminally differentiated cells to re-enter the cell cycle and proliferate in response to acute injury or environmental stress signals. In lower vertebrates, this regenerative capacity extends to several organs and remarkably culminates in precise tissue patterning, through cellular transdifferentiation and complex morphogenetic processes that can faithfully reconstruct entire body parts. Many lessons have been learned from robust regeneration models in amphibians such as the newt and axolotl. However, the dynamic interactions between the regenerating tissue, the surrounding stroma, and the host immune response, as it adapts to the actively proliferating tissue, remain ill-defined. The regenerating zone, through a sequence of distinct molecular events, adopts phenotypic plasticity and undergoes rigorous tissue remodeling that, in turn, evokes a significant inflammatory response. Complement is a primordial sentinel of the innate immune response that engages in multiple inflammatory cascades as it becomes activated during tissue injury and remodeling. In this respect, complement proteins have been implicated in tissue and organ regeneration in both urodeles and mammals. Distinct complement-triggered pathways have been shown to modulate critical responses that promote tissue reprogramming, pattern formation, and regeneration across phylogenesis. This article will discuss the mechanistic insights underlying the crosstalk of complement with cytokine and growth factor signaling pathways that drive tissue regeneration and will provide a unified conceptual framework for considering complement modulation as a novel target for regenerative therapeutics.

Seeking the source of adipocytes in adult white adipose tissues.

Adipocyte progenitors are thought to play a fundamental role in white adipose tissue (WAT) plasticity, which enables dynamic modulation of WAT metabolic and cellular characteristics in response to various stimuli. In general, two main strategies have been used to identify adipocyte progenitor cells: fluorescence-activated cell sorting (FACS)-based prospective analysis and lineage tracing. Although FACS-isolation is highly useful in defining multipotential stem cell populations for in vitro analysis and transplantation, lineage tracing is essential to identify endogenous progenitors that do, in fact, differentiate into adipocytes in vivo. Our recent lineage tracing studies have shown that cells expressing the surface marker platelet-derived growth factor receptor α (PDGFRα) give rise to white and brown adipocytes in adult WAT, depending on inductive cues. PDGFRα+ cells are a subpopulation of those expressing CD34 and Sca1, and have unique morphology whereby long dendritic processes contact numerous cell types in the microenvironment. The significant contribution of PDGFRα+ cells to browning and hyperplastic expansion of WAT leads us to propose that PDGFRα+ cells are remodeling stem cells in adult WAT. Application of advanced imaging technology and genetic tools to this progenitor population will allow greater understanding of cellular plasticity in adipose tissue.

An elasto-plastic model of avian gastrulation.

The motions observed during avian gastrulation may be simply interpreted in terms of elasto-plastic flow of sheets. Such a model allows one to calculate the flow map inside the blastodisc, hence the evolution of its shape. In addition, the model predicts that there exists a region of high stress oriented radially from the caudal pole towards the center of the blastodisc, with a tensile component oriented orthoradially. If the stress generated by cellular motion is enough to provoke a crack in the extra cellular matrix, then mesoderm ingression proceeds through a "streak" (the primitive streak) oriented from the caudal pole inwards, which relieves the stress while it creates the three germ layers. The model predicts that crack opening is next followed by crack retreat (primitive streak retreat), as mesoderm ingression continues. As mesoderm ingression proceeds around the area pellucida, similar phenomena in the anterior pole may contribute to formation of the embryo. This gives a mechanical description of avian gastrulation which complements the biochemical approach. In addition, the model provides a simple explanation to the shape of the embryo at very early stages, and possibly an explanation of the entry point of the vitteline arteries into the mesoderm.