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UID:1082@biology.technion.ac.il

DTSTART;TZID=Asia/Jerusalem:20220613T130000

DTEND;TZID=Asia/Jerusalem:20220613T140000

DTSTAMP:20220713T072650Z

URL:https://biology.technion.ac.il/en/seminars/prof-yonatan-stelzer-depart
 ment-of-molecular-cell-biology-weizmann-institute-of-science/

SUMMARY:Prof. Yonatan Stelzer\, Department of Molecular Cell Biology\, Weiz
 mann Institute of Science [No Categories]
DESCRIPTION:Location:   \n Affiliation: \n Host:\n Title: Rethinking Mamma
 lian Embryonic Development: An Integrated View of Epigenetics and Cell Com
 mitmentAbstract:One of the mostremarkable processes in biology is the deve
 lopment of a single fertilized egginto a complete multi-cellular embryo wi
 thin a short time period of rapidgrowth and cellular diversification. Yet\
 , how variation is achieved while basicunits (cells) in this system compri
 se identical genetic information\, representsa deep and fundamental open q
 uestion in biology. Single-celltechnologies are transforming our ability t
 o elucidate embryonic cellspecification. We recently generated a time-reso
 lved transcriptional model ofmouse gastrulation based on single-cell data 
 from over 150 individually isolatedand processed embryos. Since each embry
 o independently progresses at its ownpace\, toward ultimate convergence at
  a common outcome\, individual cells makingup each embryo could be placed 
 on a bona fide time continuum. This facilitateda unified flow model that c
 onsiders continuous\, parallel\, and convergeddifferentiation towards mult
 iple lineages. Based on the detailed temporalmodel\, we devised a robust e
 xperimental framework for interpreting embryonicphenotypes resulting from 
 genetic or epigenetic alterations. In this manner\, weutilize individual m
 ouse chimera embryos to systematically dissect thecell-intrinsic effects o
 f Tet-mediated DNA demethylation on embryonic cellspecification. We demons
 trate that interpretation of Tet function is dependenton separating tempor
 al\, lineage\, and cell-autonomous/inter-cellular effects.Knocking out the
  three Tet genes (Tet-TKO) in the entire embryo gives rise tomajor gastrul
 ation defects. But when Tet-TKO cells are allowed to develop in aWT niche\
 , they retain differentiation capacity to nearly all embryonic lineages.Th
 is leads to a revised conceptual framework supporting the notion thatTet-m
 ediated demethylation is dispensable towards most differentiationprograms\
 , but rater involves fine-tuning of gene expression pervasivelythroughout 
 the genome. Our work demonstrates an unbiased approach for definingintrins
 ic and extrinsic embryonic gene function based on temporaldifferentiation 
 atlases\, and disentangles the intracellular effects of thedemethylation m
 achinery from its broader tissue-level ramifications. Host: Sagi Levy 

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