Parallel Lineage-Tracing Studies Establish Fibroblasts as the Prevailing In Vivo Adipocyte Progenitor

Cattaneo, Paola; Mukherjee, Debanjan; Spinozzi, Simone; Zhang, Lunfeng; Larcher, Veronica; Stallcup, William B.; Kataoka, Hiroshi; Chen, Ju; Dimmeler, Stefanie; Evans, Sylvia M.; Guimarães-Camboa, Nuno

doi:10.1016/j.celrep.2019.12.046

Cited by 56 publications

(53 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the results are strikingly different. For example, a more recent study using Pdgfra-MerCreMer lineage traced animals found that PDGFRα+ fibroblasts gave rise to brown, beige, and white adipocytes during adult homeostasis ( Cattaneo et al, 2020 ). Another study suggests that PDGFRα+ cells are bi-potential to produce both beige and HFD-induced white adipocytes ( Lee et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, multiple genetic fate-mapping and lineage-marking studies have been conducted to understand when and where adipose progenitor cells (APCs), which are capable to proliferate and differentiate into new adipocytes, are specified ( Cattaneo et al, 2020 ; Jiang et al, 2014 ; Lee et al, 2013 ; Sanchez-Gurmaches and Guertin, 2014 ; Sanchez-Gurmaches et al, 2015 ; Sebo et al, 2018 ; Tang et al, 2008 ; Tran et al, 2012 ; Vishvanath et al, 2016 ; Wang et al, 2013 ). For example, it was reported that adult adipocytes, but not developmental adipocytes, are differentiated from perivascular smooth muscle actin (SMA, encoded by Acta2 gene) mural cell source to reside along the blood vessel walls within WAT ( Jiang et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

“…Platelet-derived growth factor receptor alpha (PDGFRα) is a membrane-bound tyrosine kinase receptor expressed in perivascular stromal cells within a variety of tissues. PDGFRα has been commonly used as a cell surface marker for adipose progenitor identification, and multiple studies have reported that PDGFRα+ cells generate adipocytes in response to adipogenic stimuli ( Berry and Rodeheffer, 2013 ; Cattaneo et al, 2020 ; Joe et al, 2010 ; Lee et al, 2012 ; Lee et al, 2012 ; Rivera-Gonzalez et al, 2016 ). For example, using Pdgfra Cre ; Rosa26R mT/mG mice, PDGFRα marks adipocytes ( Berry and Rodeheffer, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dynamic control of adipose tissue development and adult tissue homeostasis by platelet-derived growth factor receptor alpha

Shin

Pang

Park

et al. 2020

eLife

View full text Add to dashboard Cite

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 and Pdgfra gene itself are differentially required for WAT development and adult WAT homeostasis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dynamic control of adipose tissue development and adult tissue homeostasis by platelet-derived growth factor receptor alpha

Shin

Pang

Park

et al. 2020

eLife

View full text Add to dashboard Cite

show abstract

“…However, in vitro differentiation may include artificial parameters and significantly differs from MSC differentiation in vivo. Thus, in contrast to in vitro studies, previous studies have demonstrated in vivo that platelet-derived growth factor receptor alpha-expressing adventitial or capsular fibroblasts rather than MSC represent the predominant adipocyte precursor population which contributes to brown, beige, and white adipocyte differentiation [27].…”

Section: Discussionmentioning

confidence: 75%

Reversible Growth-Arrest of a Spontaneously-Derived Human MSC-Like Cell Line

Melzer

Jacobs

Dittmar

et al. 2020

IJMS

View full text Add to dashboard Cite

Life cycle limitation hampers the production of high amounts of primary human mesenchymal stroma-/stem-like cells (MSC) and limits cell source reproducibility for clinical applications. The characterization of permanently growing MSC544 revealed some differentiation capacity and the simultaneous presence of known MSC markers CD73, CD90, and CD105 even after continuous long-term culture for more than one year and 32 passages. The expression of CD13, CD29, CD44, and CD166 were identified as further surface proteins, all of which were also simultaneously detectable in various other types of primary MSC populations derived from the umbilical cord, bone marrow, and placenta suggesting MSC-like properties in the cell line. Proliferating steady state MSC544 exhibited immune-modulatory activity similar to a subpopulation of long-term growth-inhibited MSC544 after 189d of continuous culture in confluency. This confluent connective cell layer with fibroblast-like morphology can spontaneously contract and the generated space is subsequently occupied by new cells with regained proliferative capacity. Accordingly, the confluent and senescence-associated beta-galactosidase-positive MSC544 culture with about 95% G0/G1 growth-arrest resumed re-entry into the proliferative cell cycle within 3d after sub-confluent culture. The MSC544 cells remained viable during confluency and throughout this transition which was accompanied by marked changes in the release of proteins. Thus, expression of proliferation-associated genes was down-modulated in confluent MSC544 and re-expressed following sub-confluent conditions whilst telomerase (hTERT) transcripts remained detectable at similar levels in both, confluent growth-arrested and proliferating MSC544. Together with the capability of connective cell layer formation for potential therapeutic approaches, MSC544 provide a long term reproducible human cell source with constant properties.

show abstract

“…Lineage-tracing studies revealed that during development, BAT uncoupling protein 1 (UCP1)-expressing adipocytes derived from Myf5 + and Pax7 + cells, while WAT adipocyte developed from PDGFRα- and PDGFRβ-expressing cells ( Ikeda et al, 2018 ). Although cultured stromal vascular fraction (SVF) pericytes displayed multilineage differentiation capacity in vitro and in vivo ( Lin et al, 2008 ; Rodeheffer et al, 2008 ), lineage-tracing experiments investigating WAT and BAT of mice showed that pericytes did not behave as APs in vivo ( Guimarães-Camboa et al, 2017 ), while fibroblast progenitors undergoing adipogenesis acquired a beige phenotype before their differentiation into mature WAT cells ( Cattaneo et al, 2020 ). In addition to the lower number of APs found in VAT ( Tchkonia et al, 2005 ), a study utilizing the transplantation approach demonstrated that the proliferation and the differentiation of mouse APs (Lin – CD29 + CD34 + ) are influenced by the depot and their context-specific microenvironment, suggesting that APs represent functionally plastic cells ( Jeffery et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Adipogenesis in Different Body Depots and Tumor Development

Trivanović¹,

Petrinović

Djordjević

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Adipose tissue (AT) forms depots at different anatomical locations throughout the body, being in subcutaneous and visceral regions, as well as the bone marrow. These ATs differ in the adipocyte functional profile, their insulin sensitivity, adipokines' production, lipolysis, and response to pathologic conditions. Despite the recent advances in lineage tracing, which have demonstrated that individual adipose depots are composed of adipocytes derived from distinct progenitor populations, the cellular and molecular dissection of the adipose clonogenic stem cell niche is still a great challenge. Additional complexity in AT regulation is associated with tumor-induced changes that affect adipocyte phenotype. As an integrative unit of cell differentiation, AT microenvironment regulates various phenotype outcomes of differentiating adipogenic lineages, which consequently may contribute to the neoplastic phenotype manifestations. Particularly interesting is the capacity of AT to impose and support the aberrant potency of stem cells that accompanies tumor development. In this review, we summarize the current findings on the communication between adipocytes and their progenitors with tumor cells, pointing out to the coexistence of healthy and neoplastic stem cell niches developed during tumor evolution. We also discuss tumor-induced adaptations in mature adipocytes and the involvement of alternative differentiation programs.

show abstract

Parallel Lineage-Tracing Studies Establish Fibroblasts as the Prevailing In Vivo Adipocyte Progenitor

Cited by 56 publications

References 40 publications

Dynamic control of adipose tissue development and adult tissue homeostasis by platelet-derived growth factor receptor alpha

Dynamic control of adipose tissue development and adult tissue homeostasis by platelet-derived growth factor receptor alpha

Reversible Growth-Arrest of a Spontaneously-Derived Human MSC-Like Cell Line

Adipogenesis in Different Body Depots and Tumor Development

Contact Info

Product

Resources

About