Stem Cell Biology and Development

One of the major themes of our laboratory is to investigate the role of mRNA translational control during embryogenesis including embryonic stem cell self-renewal and differentiation. Since most of the research in the stem cell field has focused on transcriptional and epigenetic changes, there is a significant gap in our understanding of the role of mRNA translation in the field.

In collaboration with the Stunnenberg Lab in the Netherlands, we documented the first translational landscape of the naïve state of pluripotency in mouse embryonic stem cells (mESCs) and the exit from this state. Naïve pluripotency is a unique feature of the epiblast layer of an embryo around E4.5 which is mimicked in vitro by culturing mESCs in a defined media. Using genome-wide translational profiling, we surveyed the translating ribosome landscape during the transition out of the naïve state in mESCs.

We showed a higher ribosome density on a subset of mRNAs in the naïve state which endures strong translational buffering to maintain stable protein expression levels. This seminal work set the stage to investigate how different regulatory nodes of mRNA translation (e.g., eIF2α phosphorylation, 4E-BPs, SK6 proteins) are involved during this transition.

Model of the link between p53/p21 pathway and 4E-BP-dependent translational control in factor-induced reprogramming (Tamhasebi et al. Cell Stem Cell 2014)

Selected Papers:

  1. Mehdi Amiri, Stephen J Kiniry, Anthony P Possemato, Niaz Mahmood, Tayebeh Basiri, Catherine R Dufour, Negar Tabatabaei, Qiyun Deng, Michael A Bellucci, Keerthana Harwalkar, Matthew P Stokes, Vincent Giguère, Randal J Kaufman, Yojiro Yamanaka, Pavel V Baranov, Soroush Tahmasebi, Nahum Sonenberg (2024). Impact of eIF2α phosphorylation on the translational landscape of mouse embryonic stem cells. Cell Rep. doi: 10.1016/j.celrep.2023.113615

  2. Yaser Atlasi, Seyed Mehdi Jafarnejad, Christos G. Gkogkas, Michiel Vermeulen, Nahum Sonenberg, Hendrik G. Stunnenberg (2020). The translational landscape of ground state pluripotency. Nature Communications. doi: 10.1038/s41467-020-15449-9

  3. Soroush Tahmasebi, Mehdi Amiri, Nahum Sonenberg (2019). Translational control in stem cells. Frontiers in Genetics. doi: 10.3389/fgene.2018.00709

  4. Soroush Tahmasebi, Seyed Mehdi Jafarnejad, Ingrid S Tam, Thomas Gonatopoulos-Pournatzis, Edna Matta-Camacho, Yoshinori Tsukumo, Akiko Yanagiya, Wencheng Li, Yaser Atlasi, Maxime Caron, Ulrich Braunschweig, Dana Pearl, Arkady Khoutorsky, Christos G Gkogkas, Robert Nadon, Guillaume Bourque, Xiang-Jiao Yang, Bin Tian, Hendrik G Stunnenberg, Yojiro Yamanaka, Benjamin J Blencowe, Vincent Giguère, Nahum Sonenberg (2016). Control of embryonic stem cell self-renewal and differentiation via coordinated alternative splicing and translation of YY2. PNAS. doi: 10.1073/pnas.1615540113

  5. Soroush Tahmasebi, Tommy Alain, Vinagolu K Rajasekhar, Jiang-Ping Zhang, Masha Prager-Khoutorsky, Arkady Khoutorsky, Yildirim Dogan, Christos G Gkogkas, Emmanuel Petroulakis, Annie Sylvestre, Mohammad Ghorbani, Sarah Assadian, Yojiro Yamanaka, Julia R Vinagolu-Baur, Jose G Teodoro, Kitai Kim, Xiang-Jiao Yang, Nahum Sonenberg (2014). Multifaceted regulation of somatic cell reprogramming by mRNA translational control. Cell Stem Cell. doi: 10.1016/j.stem.2014.02.005