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A resource for discovering specific and universal biomarkers for distributed stem cells.

Noh M, Smith JL, Huh YH, Sherley JL - PLoS ONE (2011)

Bottom Line: This delineation has several significant implications.These include: 1) providing experimental evidence that DSCs in vivo undergo asymmetric self-renewal as individual cells; 2) providing an explanation why earlier attempts to define a common gene expression signature for DSCs were unsuccessful; and 3) predicting that some ASRA proteins may be ideal biomarkers for DSCs.Indeed, two ASRA proteins, CXCR6 and BTG2, and two other related self-renewal pattern associated (SRPA) proteins identified in this gene resource, LGR5 and H2A.Z, display unique asymmetric patterns of expression that have a high potential for universal and specific DSC identification.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Ajou University, Suwon, South Korea.

ABSTRACT
Specific and universal biomarkers for distributed stem cells (DSCs) have been elusive. A major barrier to discovery of such ideal DSC biomarkers is difficulty in obtaining DSCs in sufficient quantity and purity. To solve this problem, we used cell lines genetically engineered for conditional asymmetric self-renewal, the defining DSC property. In gene microarray analyses, we identified 85 genes whose expression is tightly asymmetric self-renewal associated (ASRA). The ASRA gene signature prescribed DSCs to undergo asymmetric self-renewal to a greater extent than committed progenitor cells, embryonic stem cells, or induced pluripotent stem cells. This delineation has several significant implications. These include: 1) providing experimental evidence that DSCs in vivo undergo asymmetric self-renewal as individual cells; 2) providing an explanation why earlier attempts to define a common gene expression signature for DSCs were unsuccessful; and 3) predicting that some ASRA proteins may be ideal biomarkers for DSCs. Indeed, two ASRA proteins, CXCR6 and BTG2, and two other related self-renewal pattern associated (SRPA) proteins identified in this gene resource, LGR5 and H2A.Z, display unique asymmetric patterns of expression that have a high potential for universal and specific DSC identification.

Show MeSH
Bioinformatics strategy for discovery of the 85 gene ASRA signature.ASRA genes (“ASRA-up” and “ASRA-down”) are the respective unions of two intersection sets. The ASRA-up intersection was defined as genes that were up-regulated in the ASYM state with respect to the SYM state AND up-regulated in the ASYM state with respect to the p53SYM state. The ASRA-down intersection was defined as genes that were down-regulated in the ASYM state with respect to the SYM state AND down-regulated in the ASYM state with respect to the p53SYM state (See also self-renewal pattern definitions in Fig. 1).
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pone-0022077-g002: Bioinformatics strategy for discovery of the 85 gene ASRA signature.ASRA genes (“ASRA-up” and “ASRA-down”) are the respective unions of two intersection sets. The ASRA-up intersection was defined as genes that were up-regulated in the ASYM state with respect to the SYM state AND up-regulated in the ASYM state with respect to the p53SYM state. The ASRA-down intersection was defined as genes that were down-regulated in the ASYM state with respect to the SYM state AND down-regulated in the ASYM state with respect to the p53SYM state (See also self-renewal pattern definitions in Fig. 1).

Mentions: Operationally, first we identified genes whose expression was either significantly up-regulated or significantly down-regulated in the ASYM state with respect to either the SYM state (A comparison) or the p53SYM state (B comparison) (Fig. 2; see Materials and Methods). The intersection set, ASYM v. SYM∩ASYM v. p53SYM, for respective up-regulated and down-regulated genes yielded 85 genes that met the ASRA criteria (Fig. 2; Table S1).


A resource for discovering specific and universal biomarkers for distributed stem cells.

Noh M, Smith JL, Huh YH, Sherley JL - PLoS ONE (2011)

Bioinformatics strategy for discovery of the 85 gene ASRA signature.ASRA genes (“ASRA-up” and “ASRA-down”) are the respective unions of two intersection sets. The ASRA-up intersection was defined as genes that were up-regulated in the ASYM state with respect to the SYM state AND up-regulated in the ASYM state with respect to the p53SYM state. The ASRA-down intersection was defined as genes that were down-regulated in the ASYM state with respect to the SYM state AND down-regulated in the ASYM state with respect to the p53SYM state (See also self-renewal pattern definitions in Fig. 1).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3139609&req=5

pone-0022077-g002: Bioinformatics strategy for discovery of the 85 gene ASRA signature.ASRA genes (“ASRA-up” and “ASRA-down”) are the respective unions of two intersection sets. The ASRA-up intersection was defined as genes that were up-regulated in the ASYM state with respect to the SYM state AND up-regulated in the ASYM state with respect to the p53SYM state. The ASRA-down intersection was defined as genes that were down-regulated in the ASYM state with respect to the SYM state AND down-regulated in the ASYM state with respect to the p53SYM state (See also self-renewal pattern definitions in Fig. 1).
Mentions: Operationally, first we identified genes whose expression was either significantly up-regulated or significantly down-regulated in the ASYM state with respect to either the SYM state (A comparison) or the p53SYM state (B comparison) (Fig. 2; see Materials and Methods). The intersection set, ASYM v. SYM∩ASYM v. p53SYM, for respective up-regulated and down-regulated genes yielded 85 genes that met the ASRA criteria (Fig. 2; Table S1).

Bottom Line: This delineation has several significant implications.These include: 1) providing experimental evidence that DSCs in vivo undergo asymmetric self-renewal as individual cells; 2) providing an explanation why earlier attempts to define a common gene expression signature for DSCs were unsuccessful; and 3) predicting that some ASRA proteins may be ideal biomarkers for DSCs.Indeed, two ASRA proteins, CXCR6 and BTG2, and two other related self-renewal pattern associated (SRPA) proteins identified in this gene resource, LGR5 and H2A.Z, display unique asymmetric patterns of expression that have a high potential for universal and specific DSC identification.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Ajou University, Suwon, South Korea.

ABSTRACT
Specific and universal biomarkers for distributed stem cells (DSCs) have been elusive. A major barrier to discovery of such ideal DSC biomarkers is difficulty in obtaining DSCs in sufficient quantity and purity. To solve this problem, we used cell lines genetically engineered for conditional asymmetric self-renewal, the defining DSC property. In gene microarray analyses, we identified 85 genes whose expression is tightly asymmetric self-renewal associated (ASRA). The ASRA gene signature prescribed DSCs to undergo asymmetric self-renewal to a greater extent than committed progenitor cells, embryonic stem cells, or induced pluripotent stem cells. This delineation has several significant implications. These include: 1) providing experimental evidence that DSCs in vivo undergo asymmetric self-renewal as individual cells; 2) providing an explanation why earlier attempts to define a common gene expression signature for DSCs were unsuccessful; and 3) predicting that some ASRA proteins may be ideal biomarkers for DSCs. Indeed, two ASRA proteins, CXCR6 and BTG2, and two other related self-renewal pattern associated (SRPA) proteins identified in this gene resource, LGR5 and H2A.Z, display unique asymmetric patterns of expression that have a high potential for universal and specific DSC identification.

Show MeSH