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In Lyl1^-/- mice, adipose stem cell vascular niche impairment leads to premature development of fat tissues.

ABSTRACT: Lyl1 encodes a hematopoietic- and endothelial-specific bHLH transcription factor. Lyl1-deficient mice are viable, but they display mild hematopoietic and vascular defects. Specifically, LYL1 is required for the maturation and stabilization of blood vessel endothelial adherens junctions. Here, we report that young adult Lyl1^-/- mice exhibit transient overweight associated with general expansion of adipose tissue, without signs of metabolic disorder and unrelated to food intake. The increased fat tissue development in Lyl1^-/- mice resulted from earlier differentiation of adipose stem cells (ASCs) into adipocytes through noncell autonomous mechanisms. Specifically, we found that in Lyl1^-/- mice, the adipose tissue vascular structures are immature, as indicated by their high permeability, reduced coverage by pericytes, lower recruitment of VE-cadherin and ZO1 at cell junctions, and more prone to angiogenesis. Together, our data show that in Lyl1^-/- mice, the impaired vascular compartment of the adipose niche promotes ASC differentiation, leading to early adipocyte expansion and premature ASC depletion. Our study highlights the major structural role of the adipose tissue vascular niche in coordinating stem cell self-renewal and differentiation into adipocytes.

SUBMITTER: Hussain A

PROVIDER: S-EPMC7821250 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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In Lyl1<sup>-/-</sup> mice, adipose stem cell vascular niche impairment leads to premature development of fat tissues.

Hussain Abid A Deleuze Virginie V El Kebriti Leila L Turali Hulya H Pirot Nelly N Glasson Yaël Y Mathieu Danièle D Pinet Valérie V

Stem cells (Dayton, Ohio) 20201013 1

Lyl1 encodes a hematopoietic- and endothelial-specific bHLH transcription factor. Lyl1-deficient mice are viable, but they display mild hematopoietic and vascular defects. Specifically, LYL1 is required for the maturation and stabilization of blood vessel endothelial adherens junctions. Here, we report that young adult Lyl1<sup>-/-</sup> mice exhibit transient overweight associated with general expansion of adipose tissue, without signs of metabolic disorder and unrelated to food intake. The inc ...[more]

PMID: 33022858

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Project description:BACKGROUND:The level of fat deposition in carcass is a crucial factor influencing meat quality. Guangling Large-Tailed (GLT) and Small-Tailed Han (STH) sheep are important local Chinese fat-tailed breeds that show distinct patterns of fat depots. To gain a better understanding of fat deposition, transcriptome profiles were determined by RNA-sequencing of perirenal, subcutaneous, and tail fat tissues from both the sheep breeds. The common highly expressed genes (co-genes) in all the six tissues, and the genes that were differentially expressed (DE genes) between these two breeds in the corresponding tissues were analyzed. RESULTS:Approximately 47 million clean reads were obtained for each sample, and a total of 17,267 genes were annotated. Of the 47 highly expressed co-genes, FABP4, ADIPOQ, FABP5, and CD36 were the four most highly transcribed genes among all the known genes related to adipose deposition. FHC, FHC-pseudogene, and ZC3H10 were also highly expressed genes and could, thus, have roles in fat deposition. A total of 2091, 4233, and 4131 DE genes were identified in the perirenal, subcutaneous, and tail fat tissues between the GLT and STH breeds, respectively. Gene Ontology (GO) analysis showed that some DE genes were associated with adipose metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that PPAR signaling pathway and ECM-receptor interaction were specifically enriched. Four genes, namely LOC101102230, PLTP, C1QTNF7, and OLR1 were up-regulated and two genes, SCD and UCP-1, were down-regulated in all the tested tissues of STH. Among the genes involved in ECM-receptor interaction, the genes encoding collagens, laminins, and integrins were quite different depending on the depots or the breeds. In STH, genes such as LAMB3, RELN, TNXB, and ITGA8, were identified to be up regulated and LAMB4 was observed to be down regulated. CONCLUSIONS:This study unravels the complex transcriptome profiles in sheep fat tissues, highlighting the candidate genes involved in fat deposition. Further studies are needed to investigate the roles of the candidate genes in fat deposition and in determining the meat quality of sheep.

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In Lyl1^-/- mice, adipose stem cell vascular niche impairment leads to premature development of fat tissues.

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In Lyl1<sup>-/-</sup> mice, adipose stem cell vascular niche impairment leads to premature development of fat tissues.

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In Lyl1-/- mice, adipose stem cell vascular niche impairment leads to premature development of fat tissues.

Publications

In Lyl1<sup>-/-</sup> mice, adipose stem cell vascular niche impairment leads to premature development of fat tissues.

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OmicsDI is part of the ELIXIR infrastructure

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In Lyl1^-/- mice, adipose stem cell vascular niche impairment leads to premature development of fat tissues.