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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: Remarkably, SOX17 is the key regulator of hPGC-like fate, whereas BLIMP1 represses endodermal and other somatic genes during specification of hPGCLCs.Notable mechanistic differences between mouse and human PGC specification could be attributed to their divergent embryonic development and pluripotent states, which might affect other early cell-fate decisions.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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Sequential Expression of Germ-Cell-Related Transcription Factors in Single Cells during hPGCLC Specification(A and B) Immunofluorscence analysis for (A) BLIMP1, SOX17, and TFAP2C and (B) BLIMP1 and T in cryosections of day 1–8 embryoids after hPGCLC induction. Bottom row in (B) shows high exposure (digital) image of T, indicating low but specific expression in hPGCLC. SOX17-positive or BLIMP1-positive cells are highlighted. Scale bars, 50 μm.(C) Percentage of SOX17-positive (+) cells in day 1–8 embryoids that were also TFAP2C+ or BLIMP1+. Corresponds to data in Figure 4A.(D) Percentage of BLIMP1-positive (+) cells in day 1–8 embryoids that were TFAP2C+, NANOG+, or OCT4+. Corresponds to data in Figures 4A, S4A, and S4B.(E) Summary model for dynamics of hPGCLC specification in embryoids. SOX17-positive cells are first scattered in day 1 embryoids. They gain expression of BLIMP1, TFAP2C, and NANOG sequentially and form a cluster from day 2 onward until the formation of nascent hPGCLC.
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fig4: Sequential Expression of Germ-Cell-Related Transcription Factors in Single Cells during hPGCLC Specification(A and B) Immunofluorscence analysis for (A) BLIMP1, SOX17, and TFAP2C and (B) BLIMP1 and T in cryosections of day 1–8 embryoids after hPGCLC induction. Bottom row in (B) shows high exposure (digital) image of T, indicating low but specific expression in hPGCLC. SOX17-positive or BLIMP1-positive cells are highlighted. Scale bars, 50 μm.(C) Percentage of SOX17-positive (+) cells in day 1–8 embryoids that were also TFAP2C+ or BLIMP1+. Corresponds to data in Figure 4A.(D) Percentage of BLIMP1-positive (+) cells in day 1–8 embryoids that were TFAP2C+, NANOG+, or OCT4+. Corresponds to data in Figures 4A, S4A, and S4B.(E) Summary model for dynamics of hPGCLC specification in embryoids. SOX17-positive cells are first scattered in day 1 embryoids. They gain expression of BLIMP1, TFAP2C, and NANOG sequentially and form a cluster from day 2 onward until the formation of nascent hPGCLC.

Mentions: On day 1, we first detected SOX17 in a few widely scattered cells throughout the embryoids (Figures 4A and 4E). Among the SOX17-positive (+) cells, 55% were also BLIMP1+, and 22% were TFAP2C+ (Figures 4A and 4C). However, all BLIMP1+ cells coexpressed SOX17, suggesting that SOX17 is upregulated before BLIMP1. The proportion of BLIMP1+ and TFAP2C+ cells increased to ∼70% on day 2 and to ∼90% on days 4–8 (Figures 4A and 4C). These triple-positive cells likely represent specified hPGCLCs, as they also coexpressed other key hPGC genes. However, ∼10% of single SOX17+ cells failed to undergo hPGCLC specification but persisted in day 4–8 embryoids. These may be aberrant cells or else may belong to other lineages.


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)

Sequential Expression of Germ-Cell-Related Transcription Factors in Single Cells during hPGCLC Specification(A and B) Immunofluorscence analysis for (A) BLIMP1, SOX17, and TFAP2C and (B) BLIMP1 and T in cryosections of day 1–8 embryoids after hPGCLC induction. Bottom row in (B) shows high exposure (digital) image of T, indicating low but specific expression in hPGCLC. SOX17-positive or BLIMP1-positive cells are highlighted. Scale bars, 50 μm.(C) Percentage of SOX17-positive (+) cells in day 1–8 embryoids that were also TFAP2C+ or BLIMP1+. Corresponds to data in Figure 4A.(D) Percentage of BLIMP1-positive (+) cells in day 1–8 embryoids that were TFAP2C+, NANOG+, or OCT4+. Corresponds to data in Figures 4A, S4A, and S4B.(E) Summary model for dynamics of hPGCLC specification in embryoids. SOX17-positive cells are first scattered in day 1 embryoids. They gain expression of BLIMP1, TFAP2C, and NANOG sequentially and form a cluster from day 2 onward until the formation of nascent hPGCLC.
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

fig4: Sequential Expression of Germ-Cell-Related Transcription Factors in Single Cells during hPGCLC Specification(A and B) Immunofluorscence analysis for (A) BLIMP1, SOX17, and TFAP2C and (B) BLIMP1 and T in cryosections of day 1–8 embryoids after hPGCLC induction. Bottom row in (B) shows high exposure (digital) image of T, indicating low but specific expression in hPGCLC. SOX17-positive or BLIMP1-positive cells are highlighted. Scale bars, 50 μm.(C) Percentage of SOX17-positive (+) cells in day 1–8 embryoids that were also TFAP2C+ or BLIMP1+. Corresponds to data in Figure 4A.(D) Percentage of BLIMP1-positive (+) cells in day 1–8 embryoids that were TFAP2C+, NANOG+, or OCT4+. Corresponds to data in Figures 4A, S4A, and S4B.(E) Summary model for dynamics of hPGCLC specification in embryoids. SOX17-positive cells are first scattered in day 1 embryoids. They gain expression of BLIMP1, TFAP2C, and NANOG sequentially and form a cluster from day 2 onward until the formation of nascent hPGCLC.
Mentions: On day 1, we first detected SOX17 in a few widely scattered cells throughout the embryoids (Figures 4A and 4E). Among the SOX17-positive (+) cells, 55% were also BLIMP1+, and 22% were TFAP2C+ (Figures 4A and 4C). However, all BLIMP1+ cells coexpressed SOX17, suggesting that SOX17 is upregulated before BLIMP1. The proportion of BLIMP1+ and TFAP2C+ cells increased to ∼70% on day 2 and to ∼90% on days 4–8 (Figures 4A and 4C). These triple-positive cells likely represent specified hPGCLCs, as they also coexpressed other key hPGC genes. However, ∼10% of single SOX17+ cells failed to undergo hPGCLC specification but persisted in day 4–8 embryoids. These may be aberrant cells or else may belong to other lineages.

Bottom Line: Remarkably, SOX17 is the key regulator of hPGC-like fate, whereas BLIMP1 represses endodermal and other somatic genes during specification of hPGCLCs.Notable mechanistic differences between mouse and human PGC specification could be attributed to their divergent embryonic development and pluripotent states, which might affect other early cell-fate decisions.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