Dataset Information

Activin a plays a critical role in proliferation and differentiation of human adipose progenitors.

ABSTRACT:

Objective

Growth of white adipose tissue takes place in normal development and in obesity. A pool of adipose progenitors is responsible for the formation of new adipocytes and for the potential of this tissue to expand in response to chronic energy overload. However, factors controlling self-renewal of human adipose progenitors are largely unknown. We investigated the expression profile and the role of activin A in this process.

Research design and methods

Expression of INHBA/activin A was investigated in three types of human adipose progenitors. We then analyzed at the molecular level the function of activin A during human adipogenesis. We finally investigated the status of activin A in adipose tissues of lean and obese subjects and analyzed macrophage-induced regulation of its expression.

Results

INHBA/activin A is expressed by adipose progenitors from various fat depots, and its expression dramatically decreases as progenitors differentiate into adipocytes. Activin A regulates the number of undifferentiated progenitors. Sustained activation or inhibition of the activin A pathway impairs or promotes, respectively, adipocyte differentiation via the C/EBP?-LAP and Smad2 pathway in an autocrine/paracrine manner. Activin A is expressed at higher levels in adipose tissue of obese patients compared with the expression levels in lean subjects. Indeed, activin A levels in adipose progenitors are dramatically increased by factors secreted by macrophages derived from obese adipose tissue.

Conclusions

Altogether, our data show that activin A plays a significant role in human adipogenesis. We propose a model in which macrophages that are located in adipose tissue regulate adipose progenitor self-renewal through activin A.

SUBMITTER: Zaragosi LE

PROVIDER: S-EPMC3279533 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Publications

Activin a plays a critical role in proliferation and differentiation of human adipose progenitors.

Zaragosi Laure-Emmanuelle LE Wdziekonski Brigitte B Villageois Phi P Keophiphath Mayoura M Maumus Marie M Tchkonia Tamara T Bourlier Virginie V Mohsen-Kanson Tala T Ladoux Annie A Elabd Christian C Scheideler Marcel M Trajanoski Zlatko Z Takashima Yasuhiro Y Amri Ez-Zoubir EZ Lacasa Daniele D Sengenes Coralie C Ailhaud Gérard G Clément Karine K Bouloumie Anne A Kirkland James L JL Dani Christian C

Diabetes 20100608 10

<h4>Objective</h4>Growth of white adipose tissue takes place in normal development and in obesity. A pool of adipose progenitors is responsible for the formation of new adipocytes and for the potential of this tissue to expand in response to chronic energy overload. However, factors controlling self-renewal of human adipose progenitors are largely unknown. We investigated the expression profile and the role of activin A in this process.<h4>Research design and methods</h4>Expression of INHBA/acti ...[more]

PMID: 20530742

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Project description:BackgroundNonsense mediated mRNA decay (NMD) is an RNA surveillance mechanism that controls RNA stability and ensures the speedy degradation of erroneous and unnecessary transcripts. This mechanism depends on several core factors in the exon junction complex (EJC), eIF4A3, RBM8a, Magoh, and BTZ, as well as peripheral factors to distinguish premature stop codons (PTCs) from normal stop codons in transcripts. Recently, emerging evidence has indicated that NMD factors are associated with neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID). However, the mechanism in which these factors control embryonic brain development is not clear.ResultWe found that RBM8a is critical for proliferation and differentiation in cortical neural progenitor cells (NPCs). RBM8a is highly expressed in the subventricular zone (SVZ) of the early embryonic cortex, suggesting that RBM8a may play a role in regulating NPCs. RBM8a overexpression stimulates embryonic NPC proliferation and suppresses neuronal differentiation. Conversely, knockdown of RBM8a in the neocortex reduces NPC proliferation and promotes premature neuronal differentiation. Moreover, overexpression of RBM8a suppresses cell cycle exit and keeps cortical NPCs in a proliferative state. To uncover the underlying mechanisms of this phenotype, genome-wide RNAseq was used to identify potential downstream genes of RBM8a in the brain, which have been implicated in autism and neurodevelopmental disorders. Interestingly, autism and schizophrenia risk genes are highly represented in downstream transcripts of RBM8a. In addition, RBM8a regulates multiple alternative splicing genes and NMD targets that are implicated in ASD. Taken together, this data suggests a novel role of RBM8a in the regulation of neurodevelopment.ConclusionsOur studies provide some insight into causes of mental illnesses and will facilitate the development of new therapeutic strategies for neurodevelopmental illnesses.

Dataset Information

Activin a plays a critical role in proliferation and differentiation of human adipose progenitors.

Objective

Research design and methods

Results

Conclusions

Publications

Activin a plays a critical role in proliferation and differentiation of human adipose progenitors.

Similar Datasets

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