IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v502y2013i7469d10.1038_nature12587.html
   My bibliography  Save this article

Deterministic direct reprogramming of somatic cells to pluripotency

Author

Listed:
  • Yoach Rais

    (Weizmann Institute of Science, Rehovot 76100, Israel)

  • Asaf Zviran

    (Weizmann Institute of Science, Rehovot 76100, Israel)

  • Shay Geula

    (Weizmann Institute of Science, Rehovot 76100, Israel)

  • Ohad Gafni

    (Weizmann Institute of Science, Rehovot 76100, Israel)

  • Elad Chomsky

    (Weizmann Institute of Science, Rehovot 76100, Israel)

  • Sergey Viukov

    (Weizmann Institute of Science, Rehovot 76100, Israel)

  • Abed AlFatah Mansour

    (Weizmann Institute of Science, Rehovot 76100, Israel)

  • Inbal Caspi

    (Weizmann Institute of Science, Rehovot 76100, Israel)

  • Vladislav Krupalnik

    (Weizmann Institute of Science, Rehovot 76100, Israel)

  • Mirie Zerbib

    (Weizmann Institute of Science, Rehovot 76100, Israel)

  • Itay Maza

    (Weizmann Institute of Science, Rehovot 76100, Israel)

  • Nofar Mor

    (Weizmann Institute of Science, Rehovot 76100, Israel)

  • Dror Baran

    (Weizmann Institute of Science, Rehovot 76100, Israel)

  • Leehee Weinberger

    (Weizmann Institute of Science, Rehovot 76100, Israel)

  • Diego A. Jaitin

    (Weizmann Institute of Science, Rehovot 76100, Israel)

  • David Lara-Astiaso

    (Weizmann Institute of Science, Rehovot 76100, Israel)

  • Ronnie Blecher-Gonen

    (Weizmann Institute of Science, Rehovot 76100, Israel)

  • Zohar Shipony

    (Weizmann Institute of Science, Rehovot 76100, Israel
    Weizmann Institute of Science, Rehovot 76100, Israel)

  • Zohar Mukamel

    (Weizmann Institute of Science, Rehovot 76100, Israel
    Weizmann Institute of Science, Rehovot 76100, Israel)

  • Tzachi Hagai

    (Weizmann Institute of Science, Rehovot 76100, Israel)

  • Shlomit Gilad

    (The Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot 76100, Israel)

  • Daniela Amann-Zalcenstein

    (The Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot 76100, Israel)

  • Amos Tanay

    (Weizmann Institute of Science, Rehovot 76100, Israel
    Weizmann Institute of Science, Rehovot 76100, Israel)

  • Ido Amit

    (Weizmann Institute of Science, Rehovot 76100, Israel)

  • Noa Novershtern

    (Weizmann Institute of Science, Rehovot 76100, Israel)

  • Jacob H. Hanna

    (Weizmann Institute of Science, Rehovot 76100, Israel)

Abstract

Somatic cells can be inefficiently and stochastically reprogrammed into induced pluripotent stem (iPS) cells by exogenous expression of Oct4 (also called Pou5f1), Sox2, Klf4 and Myc (hereafter referred to as OSKM). The nature of the predominant rate-limiting barrier(s) preventing the majority of cells to successfully and synchronously reprogram remains to be defined. Here we show that depleting Mbd3, a core member of the Mbd3/NuRD (nucleosome remodelling and deacetylation) repressor complex, together with OSKM transduction and reprogramming in naive pluripotency promoting conditions, result in deterministic and synchronized iPS cell reprogramming (near 100% efficiency within seven days from mouse and human cells). Our findings uncover a dichotomous molecular function for the reprogramming factors, serving to reactivate endogenous pluripotency networks while simultaneously directly recruiting the Mbd3/NuRD repressor complex that potently restrains the reactivation of OSKM downstream target genes. Subsequently, the latter interactions, which are largely depleted during early pre-implantation development in vivo, lead to a stochastic and protracted reprogramming trajectory towards pluripotency in vitro. The deterministic reprogramming approach devised here offers a novel platform for the dissection of molecular dynamics leading to establishing pluripotency at unprecedented flexibility and resolution.

Suggested Citation

  • Yoach Rais & Asaf Zviran & Shay Geula & Ohad Gafni & Elad Chomsky & Sergey Viukov & Abed AlFatah Mansour & Inbal Caspi & Vladislav Krupalnik & Mirie Zerbib & Itay Maza & Nofar Mor & Dror Baran & Leehe, 2013. "Deterministic direct reprogramming of somatic cells to pluripotency," Nature, Nature, vol. 502(7469), pages 65-70, October.
  • Handle: RePEc:nat:nature:v:502:y:2013:i:7469:d:10.1038_nature12587
    DOI: 10.1038/nature12587
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature12587
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/nature12587?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Nina Schmolka & Ino D. Karemaker & Richard Cardoso da Silva & Davide C. Recchia & Vincent Spegg & Jahnavi Bhaskaran & Michael Teske & Nathalie P. Wagenaar & Matthias Altmeyer & Tuncay Baubec, 2023. "Dissecting the roles of MBD2 isoforms and domains in regulating NuRD complex function during cellular differentiation," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Aditya Kshirsagar & Svetlana Maslov Doroshev & Anna Gorelik & Tsviya Olender & Tamar Sapir & Daisuke Tsuboi & Irit Rosenhek-Goldian & Sergey Malitsky & Maxim Itkin & Amir Argoetti & Yael Mandel-Gutfre, 2023. "LIS1 RNA-binding orchestrates the mechanosensitive properties of embryonic stem cells in AGO2-dependent and independent ways," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    3. Bo Wang & Chen Li & Jin Ming & Linlin Wu & Shicai Fang & Yi Huang & Lihui Lin & He Liu & Junqi Kuang & Chengchen Zhao & Xingnan Huang & Huijian Feng & Jing Guo & Xuejie Yang & Liman Guo & Xiaofei Zhan, 2023. "The NuRD complex cooperates with SALL4 to orchestrate reprogramming," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:502:y:2013:i:7469:d:10.1038_nature12587. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.