Human induced pluripotent stem cells: A new source for brown and white adipocytes

Hafner, Anne-Laure; Dani, Christian

doi:10.4252/wjsc.v6.i4.467

Cited by 24 publications

(15 citation statements)

References 37 publications

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“…Interestingly, the low adipogenic differentiation potential is not restricted to hiPSC-derived cells as cells derived from human hESCs display the same feature, thus ruling out the possibility that the low hiPSC-adipogenic capacity could be due to incomplete reprogramming. The low adipogenic potential of adipose progenitors is also not dependent on the methods used to derive them from PSCs (31). Overall, these observations indicated that appropriate culture conditions had to be set up to unlock hPSC-BAP adipogenesis.…”

Section: Critical Role Of the Tgfβ Pathway In Hipsc-ba Progenitor Difmentioning

confidence: 90%

Human Pluripotent Stem Cells: A Relevant Model to Identify Pathways Governing Thermogenic Adipocyte Generation

Yao¹,

Dani²,

Dani³

2020

Front. Endocrinol.

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Brown and brown-like adipocytes (BAs) are promising cell targets to counteract obesity thanks to their potential to drain and oxidize circulating glucose and triglycerides. However, the scarcity of BAs in human adults is a major limitation for energy expenditure based therapies. Enhanced characterization of BA progenitor cells (BAPs) and identification of critical pathways regulating their generation and differentiation into mature BAs would be an effective way to increase the BA mass. The identification of molecular mechanisms involved in the generation of thermogenic adipocytes is progressing substantially in mice. Much less is known in humans, thus highlighting the need for an in vitro model of human adipocyte development. Pluripotent stem cells (PSCs), i.e., embryonic stem cells and induced pluripotent stem cells, help gain insight into the different phases in the development of multiple cell types. We will discuss the capacity of human PSCs to differentiate into BAs in this review. Several groups, including ours, have reported low spontaneous adipocyte generation from PSCs. However, factors governing the differentiation of induced pluripotent stem cell-derived BA progenitors cells were recently identified, and the TGFβ signaling pathway has a pivotal role. The development of new relevant methods, such as the differentiation of hPSC-BAPs into 3D adipospheres to better mimick the lobular structure of human adipose tissue, will also be discussed. Differentiation of human PSCs into thermogenic adipocytes at high frequency provides an opportunity to characterize new targets for anti-obesity therapy.

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Section: Critical Role Of the Tgfβ Pathway In Hipsc-ba Progenitor Difmentioning

confidence: 90%

Human Pluripotent Stem Cells: A Relevant Model to Identify Pathways Governing Thermogenic Adipocyte Generation

Yao¹,

Dani²,

Dani³

2020

Front. Endocrinol.

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“…Most of the current protocols for in vitro adipocyte differentiation of hiPSCs are based on generation of embryoid bodies and/or derivation of mesenchymal stem cells prior to adipose differentiation [ 124 ]. A strategy involving overexpression of adipogenic transcription factors has also been proposed [ 125 ], but this results in a bypass of developmental pathways and therefore hampers pathophysiological studies.…”

Section: New Cellular Tools To Study Adipocyte Development mentioning

confidence: 99%

Lipodystrophic syndromes due toLMNAmutations: recent developments on biomolecular aspects, pathophysiological hypotheses and therapeutic perspectives

Vigouroux

Guénantin

Vatier

et al. 2018

Nucleus

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Mutations in LMNA, encoding A-type lamins, are responsible for laminopathies including muscular dystrophies, lipodystrophies, and premature ageing syndromes. LMNA mutations have been shown to alter nuclear structure and stiffness, binding to partners at the nuclear envelope or within the nucleoplasm, gene expression and/or prelamin A maturation. LMNA-associated lipodystrophic features, combining generalized or partial fat atrophy and metabolic alterations associated with insulin resistance, could result from altered adipocyte differentiation or from altered fat structure.Recent studies shed some light on how pathogenic A-type lamin variants could trigger lipodystrophy, metabolic complications, and precocious cardiovascular events. Alterations in adipose tissue extracellular matrix and TGF-beta signaling could initiate metabolic inflexibility. Premature senescence of vascular cells could contribute to cardiovascular complications. In affected families, metabolic alterations occur at an earlier age across generations, which could result from epigenetic deregulation induced by LMNA mutations. Novel cellular models recapitulating adipogenic developmental pathways provide scalable tools for disease modeling and therapeutic screening.

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“…PSCs represent a promising new source for white and brown adipogenesis (Elefanty and Stanley, 2012; Hafner, 2014). Adipogenic differentiation of hiPSCs has been accomplished similarly to ESCs by firstly allowing cells to form EBs and then exposing them to RA.…”

Section: Brown Adipogenesis Of Stem Cellsmentioning

confidence: 99%

Opportunities and challenges in three-dimensional brown adipogenesis of stem cells

Unser

Tian

Xie

2015

Biotechnology Advances

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The formation of brown adipose tissue (BAT) via brown adipogenesis has become a notable process due to its ability to expend energy as heat with implications in the treatment of metabolic disorders and obesity. With the advent of complexity within white adipose tissue (WAT) along with inducible brown adipocytes (also known as brite and beige), there has been a surge in deciphering adipocyte biology as well as in vivo adipogenic microenvironments. A therapeutic outcome would benefit from understanding early events in brown adipogenesis, which can be accomplished by studying cellular differentiation. Pluripotent stem cells are an efficient model for differentiation and have been directed towards both white adipogenic and brown adipogenic lineages. The stem cell microenvironment greatly contributes to terminal cell fate and as such, has been mimicked extensively by various polymers including those that can form 3D hydrogel constructs capable of biochemical and/or mechanical modifications and modulations. Using bioengineering approaches towards the creation of 3D cell culture arrangements is more beneficial than traditional 2D culture in that it better recapitulates the native tissue biochemically and biomechanically. In addition, such an approach could potentially protect the tissue formed from necrosis and allow for more efficient implantation. In this review, we highlight the promise of brown adipocytes with a focus on brown adipogenic differentiation of stem cells using bioengineering approaches, along with potential challenges and opportunities that arise when considering the energy expenditure of BAT for prospective therapeutics.

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Human induced pluripotent stem cells: A new source for brown and white adipocytes

Cited by 24 publications

References 37 publications

Human Pluripotent Stem Cells: A Relevant Model to Identify Pathways Governing Thermogenic Adipocyte Generation

Human Pluripotent Stem Cells: A Relevant Model to Identify Pathways Governing Thermogenic Adipocyte Generation

Lipodystrophic syndromes due toLMNAmutations: recent developments on biomolecular aspects, pathophysiological hypotheses and therapeutic perspectives

Opportunities and challenges in three-dimensional brown adipogenesis of stem cells

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