Exploring Derivation of Germ Cells from Pluripotent Stem Cells

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Presentation transcript:

Exploring Derivation of Germ Cells from Pluripotent Stem Cells Human Germline Cycle Exploring Derivation of Germ Cells from Pluripotent Stem Cells Specification of Primordial Germ Cells (PGCs) (~ Week 2) Azim Surani Director of Germline and Epigenomics Research University of Cambridge

Origin of primordial germ cells (PGC) specification BLIMP1 PRDM14 Day 7 Sperm Oocyte Mouse Blastocyst PGC (Day 4) SOX17 BLIMP1 Day 14 Zygote Sperm Oocyte Blastocyst PGC (Day 7) Human Mechanism of PGC specification is not conserved between mouse and human

Primordial germ cell (PGC) Germ Cells versus Soma August Weissman (1834-1914) Reprogramming Induced pluripotent stem cell (iPSC) Soma (Skin cells etc… ) Primordial germ cell (PGC) Oocyte Sperm Breaking the Weissman’s barrier Totipotent zygote Soma PGC Germline is “immortal” Endless generations…

Making gametes from mouse induced pluripotent stem cells Blastocyst Maturation in mice Sperm Oocyte Viable young Reprogramming PGC-like cell (PGCLC) Somatic cell Pluripotent stem cell (iPS cell, ES cell) Viable gametes and live young generated from mouse induced pluripotent stem cells Hayashi K., et al. Cell (2011) Hayashi K., et al. Science (2012)

PGCLC share key properties Human primordial germ cells (PGCs) from induced pluripotent stem cells in vivo PGC at wk4 PGCLC share key properties with PGCs in vivo Blastocyst PGCLC Reprogramming Sperm Oocyte Zygote Blastocyst PGD Putative gametes in vitro Skin cell Induced pluripotent stem cell Genome editing Genome sequencing Irie N., et al. Cell (2015); Tang WWC., et al., Cell (2015)