Amplification of Adipogenic Commitment by VSTM2A

Secco, Blandine; Camiré, Étienne; Brière, Marc Antoine; Caron, Alexandre; Billong, Armande; Gélinas, Yves; Lemay, Anne Marie; Tharp, Kevin M.; Lee, Peter L.; Gobeil, Stéphane; Guimond, Jean; Patey, Natacha; Guertin, David A.; Stahl, Andreas; Haddad, Élie; Marsolais, David; Bossé, Yohan; Birsoy, Kıvanç; Laplante, Mathieu

doi:10.1016/j.celrep.2016.12.015

Cited by 21 publications

(14 citation statements)

References 45 publications

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“…Markers for brown (MYF5, PAX5, MYOD1 [ 22 ]) or beige/bright (MYF11 [ 23 ]) adipocyte progenitors were absent in our data set. A few cells expressed low levels of CD24 [ 8 ] while no cells expressed VSTM2A [ 9 ], suggesting that neither of these markers label ASCs in humans.…”

Section: Discussionmentioning

confidence: 99%

“…ASCs are the most abundant cell type in the stroma vascular fraction (SVF) of WAT, and murine studies have suggested the presence of several ASC populations displaying different capacities to undergo adipogenesis [ 8 , 9 ]. Some markers that enrich for ASCs with marked differentiation capacity have also been identified in humans, including CD34 [ 10 ] and CD36 [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Single cell transcriptomics suggest that human adipocyte progenitor cells constitute a homogeneous cell population

et al. 2017

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Regulation of adipose tissue stem cells (ASCs) and adipogenesis impact the development of excess body fat-related metabolic complications. Animal studies have suggested the presence of distinct subtypes of ASCs with different differentiation properties. In addition, ASCs are becoming the biggest source of mesenchymal stem cells used in therapies, which requires deep characterization. Using unbiased single cell transcriptomics we aimed to characterize ASC populations in human subcutaneous white adipose tissue (scWAT). The transcriptomes of 574 single cells from the WAT total stroma vascular fraction (SVF) of four healthy women were analyzed by clustering and t-distributed stochastic neighbor embedding visualization. The identified cell populations were then mapped to cell types present in WAT using data from gene expression microarray profiling of flow cytometry-sorted SVF. Cells clustered into four distinct populations: three adipose tissue-resident macrophage subtypes and one large, homogeneous population of ASCs. While pseudotemporal ordering analysis indicated that the ASCs were in slightly different differentiation stages, the differences in gene expression were small and could not distinguish distinct ASC subtypes. Altogether, in healthy individuals, ASCs seem to constitute a single homogeneous cell population that cannot be subdivided by single cell transcriptomics, suggesting a common origin for human adipocytes in scWAT.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0701-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Single cell transcriptomics suggest that human adipocyte progenitor cells constitute a homogeneous cell population

et al. 2017

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“…VSTM2A protein composes of 240 amino acid (aa), containing a potential 25-aa N-terminal signal peptide, two putative glycosylation sites, and a single immunoglobulin V-set domain. Previous study suggested a role of VSTM2A in the regulation of the preadipocyte cell differentiation 6. VSTM2A was markedly reduced in colorectal adenoma compared with the normal mucosa in a transcriptome profiling of 32 patients 7.…”

Section: Introductionmentioning

confidence: 82%

VSTM2A suppresses colorectal cancer and antagonizes Wnt signaling receptor LRP6

Dong

Zhang

Kang³

et al. 2019

Theranostics

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Hyperactivation of Wnt/β-catenin signaling pathway is a critical step in colorectal tumorigenesis. In this study, we identified that V-set and transmembrane domain containing 2A (VSTM2A) was a top-downregulated secreted protein that negatively regulated Wnt singling pathways in colorectal cancer (CRC). We investigated the functional mechanisms and clinical implication of VSTM2A in CRC.Methods: Function of VSTM2A was investigated in vitro and in vivo. VSTM2A binding partner was identified by mass spectrometry, immunoprecipitation and Western blot. The clinical impact of VSTM2A was assessed in 355 CRC patients and TCGA cohort.Results: VSTM2A protein was prominently silenced in CRC tumor tissues and cell lines mediated by its promoter hypermethylation. VSTM2A DNA promoter hypermethylation and VSTM2A protein downregulation was associated with poor survival of CRC patients. Ectopic expression of VSTM2A inhibited colon cancer cell lines and organoid growth, induced CRC cells apoptosis, inhibited cell migration and invasion, and suppressed growth of xenograft tumors in nude mice. VSTM2A was released from CRC cells through a canonical secretion pathway. Secreted VSTM2A significantly suppressed Wnt signaling pathway in colon cancer cells. Wnt signaling co-receptor LDL receptor related protein 6 (LRP6) was identified as a cell membrane binding partner of VSTM2A. Using deletion/mutation and immunoprecipitation, we demonstrated that VSTM2A bound to LRP6 E1-4 domain with its IgV domain. VSTM2A suppressed LRP6 phosphorylation in a time and dose dependent manner, and induced LRP6 endocytosis and lysosome-mediated degradation, which collectively contributing to the inactivation of Wnt signaling.Conclusions: VSTM2A is a novel antagonist of canonical Wnt signaling by directly binding to LRP6 and induces LRP6 endocytosis and degradation. VSTM2A is a potential prognostic biomarker for the outcome of CRC patients.

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“…LOXL2 [42,43], LIMS1 [44], NINJ2 [41], HVCN1 [45,46], TMEM79 [47], VSTM2A [48], FNDC4 [49] Interestingly, especially among antigens recognized by INSIP patient sera, there are many extracellular or membrane proteins, which are accessible by antibodies even under normal conditions. This suggests that the antigen-antibody interactions may be implicated in the pathogenesis or clinical course of disease.…”

Section: Intracellular Antigens Extracellular or Membrane Antigensmentioning

confidence: 99%

“…In addition to these three proteins, we identified other extracellular or membrane proteins including transmembrane protein 254 (TMEM254), prokineticin 1 (PROK1) [39], and CGRP receptor component (CRCP) [40], as targets of IPF natural autoantibodies. We also identified extracellular or membrane proteins including NINJ2 [41], transmembrane protein 79 (TMEM79) [47], V-Set and transmembrane domain containing 2A (VSTM2A) [48], and fibronectin type III domain containing 4 (FNDC4) [49], as targets of INSIP natural autoantibodies (Table 1).…”

Section: Intracellular Antigens Extracellular or Membrane Antigensmentioning

confidence: 99%

Natural Autoantibodies in Chronic Pulmonary Diseases

Fukushima

Tsujino

Futami

et al. 2020

IJMS

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In autoantibody-mediated autoimmune diseases, pathogenic autoantibodies generated by a failure of central or peripheral tolerance, have different effects mediated by a variety of mechanisms. Interestingly, even non-autoimmune chronic diseases have a set of disease-specific natural autoantibodies that are maintained for a long time. Because most of these natural autoantibodies target intracellular proteins or long non-coding RNAs, they are speculated to be non-pathological and have some important as yet unrecognized physiological functions such as debris clearance. Recently, we revealed a set of disease-specific natural autoantibodies of chronic pulmonary diseases with unknown etiology by protein arrays that enable detection of specific autoantibodies against >8000 targets. Surprisingly, some of the targeted antigens of disease-specific autoantibodies were subsequently reported by other laboratories as strongly associated with the disease, suggesting that these antigens reflect the pathology of each disease. Furthermore, some of these autoantibodies that target extracellular antigens might modify the original course of each disease. Here, we review the disease-specific natural autoantibodies of chronic pulmonary diseases, including chronic fibrosing idiopathic interstitial pneumonias, sarcoidosis, and autoimmune pulmonary alveolar proteinosis, and discuss their utility and effects.

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Amplification of Adipogenic Commitment by VSTM2A

Cited by 21 publications

References 45 publications

Single cell transcriptomics suggest that human adipocyte progenitor cells constitute a homogeneous cell population

Single cell transcriptomics suggest that human adipocyte progenitor cells constitute a homogeneous cell population

VSTM2A suppresses colorectal cancer and antagonizes Wnt signaling receptor LRP6

Natural Autoantibodies in Chronic Pulmonary Diseases

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