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SOX17 is a critical specifier of human primordial germ cell fate.

Irie N, Weinberger L, Tang WW, Kobayashi T, Viukov S, Manor YS, Dietmann S, Hanna JH, Surani MA - Cell (2014)

Bottom Line: Here, we demonstrate specification of hPGC-like cells (hPGCLCs) from germline competent pluripotent stem cells.Remarkably, SOX17 is the key regulator of hPGC-like fate, whereas BLIMP1 represses endodermal and other somatic genes during specification of hPGCLCs.We have established a foundation for future studies on resetting of the epigenome in hPGCLCs and hPGCs for totipotency and the transmission of genetic and epigenetic information.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Cancer Research UK Gurdon Institute, Tennis Court Road, University of Cambridge, Cambridge CB2 1QN, UK; Department of Physiology, Development and Neuroscience, Downing Street, University of Cambridge, Cambridge CB2 3EG, UK; Wellcome Trust-Medical Research Council Stem Cell Institute, Tennis Court Road, University of Cambridge, Cambridge CB2 3EG, UK.

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Global Transcriptome Analysis of hPGCLC, Related to Figure 2(A) Pearson correlation heat map of gene expression (log2(normalized read counts)) in various samples with unsupervised hierarchical clustering. The color key indicates the correlation coefficient.(B) Two-dimensional principal components analysis of gene expression (PC3 against PC2) of the indicated samples (left panel). A corresponding loadings plot indicates the weight of various genes on PC2 and PC3 (right panel). Gene names are color-coded to illustrate association with pluripotency (black), early germ cell development (green), late germ cell development (red) and gonadal somatic cell development (blue). Arrowline indicates potential germline progression from 4i hESC via hPGCLC to gonadal hPGC.
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figs2: Global Transcriptome Analysis of hPGCLC, Related to Figure 2(A) Pearson correlation heat map of gene expression (log2(normalized read counts)) in various samples with unsupervised hierarchical clustering. The color key indicates the correlation coefficient.(B) Two-dimensional principal components analysis of gene expression (PC3 against PC2) of the indicated samples (left panel). A corresponding loadings plot indicates the weight of various genes on PC2 and PC3 (right panel). Gene names are color-coded to illustrate association with pluripotency (black), early germ cell development (green), late germ cell development (red) and gonadal somatic cell development (blue). Arrowline indicates potential germline progression from 4i hESC via hPGCLC to gonadal hPGC.

Mentions: Unsupervised hierarchical clustering of global gene expression showed that the hPGCLCs clustered with hPGCs and TCam-2, whereas 4i hESCs and preinduced cells (4i hESCs treated with bFGF and TGFβ for 2 days) clustered together in another branch away from gonadal somatic cells (soma) (Figure 2A). Consistently, hPGCs were globally more related to hPGCLCs (Pearson correlation coefficient [r] = 0.85) and TCam-2 (r = 0.818) than to 4i hESCs (r = 0.799) and preinduced cells (r = 0.773) (Figure S2A).


SOX17 is a critical specifier of human primordial germ cell fate.

Irie N, Weinberger L, Tang WW, Kobayashi T, Viukov S, Manor YS, Dietmann S, Hanna JH, Surani MA - Cell (2014)

Global Transcriptome Analysis of hPGCLC, Related to Figure 2(A) Pearson correlation heat map of gene expression (log2(normalized read counts)) in various samples with unsupervised hierarchical clustering. The color key indicates the correlation coefficient.(B) Two-dimensional principal components analysis of gene expression (PC3 against PC2) of the indicated samples (left panel). A corresponding loadings plot indicates the weight of various genes on PC2 and PC3 (right panel). Gene names are color-coded to illustrate association with pluripotency (black), early germ cell development (green), late germ cell development (red) and gonadal somatic cell development (blue). Arrowline indicates potential germline progression from 4i hESC via hPGCLC to gonadal hPGC.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4310934&req=5

figs2: Global Transcriptome Analysis of hPGCLC, Related to Figure 2(A) Pearson correlation heat map of gene expression (log2(normalized read counts)) in various samples with unsupervised hierarchical clustering. The color key indicates the correlation coefficient.(B) Two-dimensional principal components analysis of gene expression (PC3 against PC2) of the indicated samples (left panel). A corresponding loadings plot indicates the weight of various genes on PC2 and PC3 (right panel). Gene names are color-coded to illustrate association with pluripotency (black), early germ cell development (green), late germ cell development (red) and gonadal somatic cell development (blue). Arrowline indicates potential germline progression from 4i hESC via hPGCLC to gonadal hPGC.
Mentions: Unsupervised hierarchical clustering of global gene expression showed that the hPGCLCs clustered with hPGCs and TCam-2, whereas 4i hESCs and preinduced cells (4i hESCs treated with bFGF and TGFβ for 2 days) clustered together in another branch away from gonadal somatic cells (soma) (Figure 2A). Consistently, hPGCs were globally more related to hPGCLCs (Pearson correlation coefficient [r] = 0.85) and TCam-2 (r = 0.818) than to 4i hESCs (r = 0.799) and preinduced cells (r = 0.773) (Figure S2A).

Bottom Line: Here, we demonstrate specification of hPGC-like cells (hPGCLCs) from germline competent pluripotent stem cells.Remarkably, SOX17 is the key regulator of hPGC-like fate, whereas BLIMP1 represses endodermal and other somatic genes during specification of hPGCLCs.We have established a foundation for future studies on resetting of the epigenome in hPGCLCs and hPGCs for totipotency and the transmission of genetic and epigenetic information.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Cancer Research UK Gurdon Institute, Tennis Court Road, University of Cambridge, Cambridge CB2 1QN, UK; Department of Physiology, Development and Neuroscience, Downing Street, University of Cambridge, Cambridge CB2 3EG, UK; Wellcome Trust-Medical Research Council Stem Cell Institute, Tennis Court Road, University of Cambridge, Cambridge CB2 3EG, UK.

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Related in: MedlinePlus