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Azim Surani

2018 SuraniAzim Surani PhD CBE FRS FMedSci, Director of Germline and Epigenomics Research, Wellcome Senior Investigator, Member of the Physiology, Development and Neuroscience Department.

Contact by email | Europe PMC | Pubmed

2018 Winner Canada Gairdner International Award

 

 

Human germ cell specification, programming and epigenetic inheritance

What makes a germline cell? We study primordial germ cells (PGCs), precursors to eggs and sperm, in the early embryo. We have established principles of early human development with a focus on human PGC specification. A unique epigenetic resetting follows in the germline after hPGC specification. Our work shows that SOX17 is the key regulator of human, but not mouse, germ cell fate.

By developing in vitro models, and with authentic hPGCs from human embryos, we have also established how pluripotent stem cells gain competence for germ cell and somatic fates in human. These findings are important for studies on human pluripotent stem cells and regenerative medicine. The inheritance of genetic and epigenetic information from the germline through the totipotent state affects human development and disease for generations.

Whereas SOX17–BLIMP1 apparently initiate the epigenetic programme in early human germline, BLIMP1–PRDM14 play a similar role in mouse germline, resulting in the comprehensive erasure of DNA methylation (except for some resistant loci), X-reactivation and imprints erasure, followed by re-establishment of sperm- and oocyte-specific imprints. Defects in these gamete-specific imprints lead to a variety of human disease syndromes.

We have also examined mitochondrial DNA (mtDNA) in PGCs, showing evidence for selection against mitochondria that harbour mutations. This mechanism is imperfect and can account for inherited mtDNA disorders.

Selected publications:

• Hackett JA et al. (2018) Tracing the transitions from pluripotency to germ cell fate with CRISPR screening. Nat Commun 9(1): 4292.

• Floros VI et al. (2018) Segregation of mitochondrial DNA heteroplasmy through a developmental genetic bottleneck in human embryos. Nat Cell Biol 20(2): 144-151. 

• Kobayashi T et al. (2017) Principles of early human development and germ cell program from conserved model systems. Nature 546(7658): 416-420.

• Murakami K et al. (2016) NANOG alone induces germ cells in primed epiblast in vitro by activation of enhancers. Nature 529: 403–407.

• Tang WWC et al. (2015) A Unique Gene Regulatory Network Resets the Human Germline Epigenome for Development. Cell 161(6): 1453–1467.

• Irie N, Weinberger L, Tang WWC, Kobayashi T, Viukov S, Manor Y, Dietmann S, Hanna JH, Surani MA  (2015) SOX17 is a critical specifier of human primordial germ cell fate. Cell 160, 253-268 

• Hackett JA, Sengupta R, Zylicz JJ, Murakami K, Lee C, Down TA and Surani MA (2012) Germline DNA demethylation dynamics and imprint erasure through 5-hydoxymethylcytosine. Science, 339, 448-452

• Tang F, Barbacioru C, Bao S, Lee C, Nordman E, Xiaohui W, Lao K, Surani MA (2010) Tracing the derivation of embryonic stem cells from the inner cell mass by single-cell RNA-seq analysis. Cell Stem Cell 6 (5-2) 468-478

Surani group (Nov18 to Feb19)

Video: Azim Surani and genomic imprinting

Co-workers

João Alves Lopes • Oriol Caritg • Aracely Castillo • Elena Drousioti • Lynn Froggett • Wolfram Gruhn • Mei Gu • Nadia Gueorguieva • Naoko Irie • Yong-Hee Kim • Sun Min Lee • Jitesh Neupane • Merrick Pierson Smela • Walfred Tang • Freddy Wong • Qi Yin