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Professor Yi Zhang – Howard Hughes Medical Institute

14/02/2025 9:00 am - 14/02/2025 10:00 am
Location
Davis Auditorium

WEHI Special Genetics and Gene Regulation Seminar hosted by Professor Marnie Blewitt and Dr Stephin Vervoort

Professor Yi Zhang
Fred S. Rosen Professor of Pediatrics, Professor of Genetics; Howard Hughes Medical Institute, Harvard Medical School and Boston Children’s Hospital, USA

Transcription regulation in naïve pluripotent stem cell specification  and hematopoietic stem cell aging

Davis Auditorium

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Including Q&A session

 

The establishment of naïve pluripotency is a continuous process starting with the generation of inner cell mass (ICM) which then differentiating into epiblast (EPI). Recent studies have revealed key transcription factors (TFs) for ICM formation, but which TFs initiate EPI specification remains unknown. By integrating transcriptome and chromatin accessibility during mouse naïve pluripotent stem cell specification, we identified and demonstrated that GABPA is not only a regulator of major ZGA, but also a master EPI specifier required for naïve pluripotency establishment during E3.5 to E4.5 transition.

Aging is a process accompanied by functional decline in tissues and organs with great social and medical consequences. As the cell source of hematopoietic and immune systems, aging-associated functional decline in hematopoietic stem cells (HSCs) play a critical role in whole body aging. Through comprehensive molecular and functional analyses, we identified a subset of HSCs in aged mice that exhibit “younger” molecular profiles and functions. We show that this “younger” HSCs from old mice can effectively differentiate into downstream lineage cells but not their “older” counterparts. Notably, transplantation of the “younger” HSCs attenuates aging phenotypes and prolongs the lifespan of elderly mice compared to those transplanted with unselected or the “older” HSCs. Importantly, reducing the dysfunctional “older” HSCs can alleviate aging phenotypes in old recipient mice. Thus, our study demonstrates the presence of “younger” HSCs in old mice, and that aging-associated functional decline can be mitigated by removing dysfunctional HSCs.

Yi Zhang is a Fred Rosen Chair Professor of the Department of Genetics and Department of Pediatrics of the Harvard Medical School and Boston Children’s Hospital. His major interest has been the epigenetic basis of gene expression in early development, stem cell reprogramming and aging, as well as reward-related learning and memory. He is also interested in how dysregulation of epigenetic enzymes contributes to various human diseases including cancer and drug addiction.

Dr. Zhang has made fundamental contributions to the epigenetics field through systematic identifying and characterizing chromatin modifying enzymes, including the nucleosome remodeling and deacetylase (NuRD) complex, histone methyltransferases (e.g. Ezh2/PRC2, Dot1L), the JmjC-containing histone demethylases, histone H2A ubiquitin E3 ligase PRC1, and the TET family of 5-methylcytosine dioxygenases. In addition to identifying these critical epigenetic enzymes, he contributed in elucidation the mechanisms underlying classic epigenetic phenomena, including Polycomb silencing, genomic imprinting, and X-chromosome inactivation. Furthermore, his lab has greatly improved the animal cloning technology by identifying and overcoming two of the most important epigenetic barriers of cloning, as well as helped in developing PRC2/EZH2 inhibitor tazemetostat, an FDA approved drug for epithliod sarcoma and follicular lymphoma. Dr. Zhang was named a Top 10 author of high impact papers in Genetics and Molecular Biology (2002-2006), and one of the most influential scientists in the world by ScienceWatch. He has published over 190 high impact papers with more than 90,000 citations and an H-index of 123.

 

 

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