IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-35938-x.html
   My bibliography  Save this article

DNMT3B supports meso-endoderm differentiation from mouse embryonic stem cells

Author

Listed:
  • Andrea Lauria

    (Università di Torino
    Italian Institute for Genomic Medicine (IIGM))

  • Guohua Meng

    (Università di Torino
    Italian Institute for Genomic Medicine (IIGM))

  • Valentina Proserpio

    (Università di Torino
    Italian Institute for Genomic Medicine (IIGM))

  • Stefania Rapelli

    (Università di Torino)

  • Mara Maldotti

    (Università di Torino
    Italian Institute for Genomic Medicine (IIGM))

  • Isabelle Laurence Polignano

    (Università di Torino
    Italian Institute for Genomic Medicine (IIGM))

  • Francesca Anselmi

    (Università di Torino
    Italian Institute for Genomic Medicine (IIGM))

  • Danny Incarnato

    (University of Groningen)

  • Anna Krepelova

    (Università di Torino)

  • Daniela Donna

    (Università di Torino)

  • Chiara Levra Levron

    (Università di Torino)

  • Giacomo Donati

    (Università di Torino)

  • Ivan Molineris

    (Università di Torino
    Italian Institute for Genomic Medicine (IIGM))

  • Francesco Neri

    (Università di Torino)

  • Salvatore Oliviero

    (Università di Torino
    Italian Institute for Genomic Medicine (IIGM))

Abstract

The correct establishment of DNA methylation patterns during mouse early development is essential for cell fate specification. However, the molecular targets as well as the mechanisms that determine the specificity of the de novo methylation machinery during differentiation are not completely elucidated. Here we show that the DNMT3B-dependent DNA methylation of key developmental regulatory regions at epiblast-like cells (EpiLCs) provides an epigenetic priming that ensures flawless commitment at later stages. Using in vitro stem cell differentiation and loss of function experiments combined with high-throughput genome-wide bisulfite-, bulk-, and single cell RNA-sequencing we dissected the specific role of DNMT3B in cell fate. We identify DNMT3B-dependent regulatory elements on the genome which, in Dnmt3b knockout (3BKO), impair the differentiation into meso-endodermal (ME) progenitors and redirect EpiLCs towards the neuro-ectodermal lineages. Moreover, ectopic expression of DNMT3B in 3BKO re-establishes the DNA methylation of the master regulator Sox2 super-enhancer, downmodulates its expression, and restores the expression of ME markers. Taken together, our data reveal that DNMT3B-dependent methylation at the epiblast stage is essential for the priming of the meso-endodermal lineages and provide functional characterization of the de novo DNMTs during EpiLCs lineage determination.

Suggested Citation

  • Andrea Lauria & Guohua Meng & Valentina Proserpio & Stefania Rapelli & Mara Maldotti & Isabelle Laurence Polignano & Francesca Anselmi & Danny Incarnato & Anna Krepelova & Daniela Donna & Chiara Levra, 2023. "DNMT3B supports meso-endoderm differentiation from mouse embryonic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35938-x
    DOI: 10.1038/s41467-023-35938-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-35938-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-35938-x?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
    ---><---

    References listed on IDEAS

    as
    1. Paul Adrian Ginno & Dimos Gaidatzis & Angelika Feldmann & Leslie Hoerner & Dilek Imanci & Lukas Burger & Frederic Zilbermann & Antoine H. F. M. Peters & Frank Edenhofer & Sébastien A. Smallwood & Arna, 2020. "A genome-scale map of DNA methylation turnover identifies site-specific dependencies of DNMT and TET activity," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    2. Zachary D. Smith & Michelle M. Chan & Tarjei S. Mikkelsen & Hongcang Gu & Andreas Gnirke & Aviv Regev & Alexander Meissner, 2012. "A unique regulatory phase of DNA methylation in the early mammalian embryo," Nature, Nature, vol. 484(7394), pages 339-344, April.
    3. Pawel Nowialis & Katarina Lopusna & Jana Opavska & Staci L. Haney & Ajay Abraham & Peike Sheng & Alberto Riva & Amarnath Natarajan & Olga Guryanova & Melanie Simpson & Ryan Hlady & Mingyi Xie & Rene O, 2019. "Catalytically inactive Dnmt3b rescues mouse embryonic development by accessory and repressive functions," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    4. Linfeng Gao & Max Emperle & Yiran Guo & Sara A. Grimm & Wendan Ren & Sabrina Adam & Hidetaka Uryu & Zhi-Min Zhang & Dongliang Chen & Jiekai Yin & Michael Dukatz & Hiwot Anteneh & Renata Z. Jurkowska &, 2020. "Comprehensive structure-function characterization of DNMT3B and DNMT3A reveals distinctive de novo DNA methylation mechanisms," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    5. Francesco Neri & Stefania Rapelli & Anna Krepelova & Danny Incarnato & Caterina Parlato & Giulia Basile & Mara Maldotti & Francesca Anselmi & Salvatore Oliviero, 2017. "Intragenic DNA methylation prevents spurious transcription initiation," Nature, Nature, vol. 543(7643), pages 72-77, March.
    6. Emma Bell & Edward W. Curry & Wout Megchelenbrink & Luc Jouneau & Vincent Brochard & Rute A. Tomaz & King Hang T. Mau & Yaser Atlasi & Roshni A. de Souza & Hendrik Marks & Hendrik G. Stunnenberg & Ali, 2020. "Dynamic CpG methylation delineates subregions within super-enhancers selectively decommissioned at the exit from naive pluripotency," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    7. Paul J. Tesar & Josh G. Chenoweth & Frances A. Brook & Timothy J. Davies & Edward P. Evans & David L. Mack & Richard L. Gardner & Ronald D. G. McKay, 2007. "New cell lines from mouse epiblast share defining features with human embryonic stem cells," Nature, Nature, vol. 448(7150), pages 196-199, July.
    8. Thomas Dahlet & Andrea Argüeso Lleida & Hala Al Adhami & Michael Dumas & Ambre Bender & Richard P. Ngondo & Manon Tanguy & Judith Vallet & Ghislain Auclair & Anaïs F. Bardet & Michael Weber, 2020. "Genome-wide analysis in the mouse embryo reveals the importance of DNA methylation for transcription integrity," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    9. Stefanie Grosswendt & Helene Kretzmer & Zachary D. Smith & Abhishek Sampath Kumar & Sara Hetzel & Lars Wittler & Sven Klages & Bernd Timmermann & Shankar Mukherji & Alexander Meissner, 2020. "Epigenetic regulator function through mouse gastrulation," Nature, Nature, vol. 584(7819), pages 102-108, August.
    10. Masaki Yagi & Mio Kabata & Akito Tanaka & Tomoyo Ukai & Sho Ohta & Kazuhiko Nakabayashi & Masahito Shimizu & Kenichiro Hata & Alexander Meissner & Takuya Yamamoto & Yasuhiro Yamada, 2020. "Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    11. Junyue Cao & Malte Spielmann & Xiaojie Qiu & Xingfan Huang & Daniel M. Ibrahim & Andrew J. Hill & Fan Zhang & Stefan Mundlos & Lena Christiansen & Frank J. Steemers & Cole Trapnell & Jay Shendure, 2019. "The single-cell transcriptional landscape of mammalian organogenesis," Nature, Nature, vol. 566(7745), pages 496-502, February.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Simon Andrews & Christel Krueger & Maravillas Mellado-Lopez & Myriam Hemberger & Wendy Dean & Vicente Perez-Garcia & Courtney W. Hanna, 2023. "Mechanisms and function of de novo DNA methylation in placental development reveals an essential role for DNMT3B," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Francesco Panariello & Onelia Gagliano & Camilla Luni & Antonio Grimaldi & Silvia Angiolillo & Wei Qin & Anna Manfredi & Patrizia Annunziata & Shaked Slovin & Lorenzo Vaccaro & Sara Riccardo & Valenti, 2023. "Cellular population dynamics shape the route to human pluripotency," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Woranop Sukparangsi & Elena Morganti & Molly Lowndes & Hélène Mayeur & Melanie Weisser & Fella Hammachi & Hanna Peradziryi & Fabian Roske & Jurriaan Hölzenspies & Alessandra Livigni & Benoit Gilbert G, 2022. "Evolutionary origin of vertebrate OCT4/POU5 functions in supporting pluripotency," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    4. Ariane Lismer & Sarah Kimmins, 2023. "Emerging evidence that the mammalian sperm epigenome serves as a template for embryo development," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    5. André Bortolini Silveira & Alexandre Houy & Olivier Ganier & Begüm Özemek & Sandra Vanhuele & Anne Vincent-Salomon & Nathalie Cassoux & Pascale Mariani & Gaelle Pierron & Serge Leyvraz & Damian Rieke , 2024. "Base-excision repair pathway shapes 5-methylcytosine deamination signatures in pan-cancer genomes," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    6. Kosuke Yamaguchi & Xiaoying Chen & Brianna Rodgers & Fumihito Miura & Pavel Bashtrykov & Frédéric Bonhomme & Catalina Salinas-Luypaert & Deis Haxholli & Nicole Gutekunst & Bihter Özdemir Aygenli & Lau, 2024. "Non-canonical functions of UHRF1 maintain DNA methylation homeostasis in cancer cells," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    7. Qing Li & Jiansen Lu & Xidi Yin & Yunjian Chang & Chao Wang & Meng Yan & Li Feng & Yanbo Cheng & Yun Gao & Beiying Xu & Yao Zhang & Yingyi Wang & Guizhong Cui & Luang Xu & Yidi Sun & Rong Zeng & Yixue, 2023. "Base editing-mediated one-step inactivation of the Dnmt gene family reveals critical roles of DNA methylation during mouse gastrulation," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    8. Kentaro Mochizuki & Jafar Sharif & Kenjiro Shirane & Kousuke Uranishi & Aaron B. Bogutz & Sanne M. Janssen & Ayumu Suzuki & Akihiko Okuda & Haruhiko Koseki & Matthew C. Lorincz, 2021. "Repression of germline genes by PRC1.6 and SETDB1 in the early embryo precedes DNA methylation-mediated silencing," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    9. Sivakamasundari Vijayakumar & Roberta Sala & Gugene Kang & Angela Chen & Michelle Ann Pablo & Abidemi Ismail Adebayo & Andrea Cipriano & Jonas L. Fowler & Danielle L. Gomes & Lay Teng Ang & Kyle M. Lo, 2023. "Monolayer platform to generate and purify primordial germ-like cells in vitro provides insights into human germline specification," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    10. Brian DeVeale & Leqian Liu & Ryan Boileau & Jennifer Swindlehurst-Chan & Bryan Marsh & Jacob W. Freimer & Adam Abate & Robert Blelloch, 2022. "G1/S restriction point coordinates phasic gene expression and cell differentiation," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    11. Zengyu Shao & Jiuwei Lu & Nelli Khudaverdyan & Jikui Song, 2024. "Multi-layered heterochromatin interaction as a switch for DIM2-mediated DNA methylation," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    12. Yasuaki Uehara & Yusuke Tanaka & Shuyang Zhao & Nikolaos M. Nikolaidis & Lori B. Pitstick & Huixing Wu & Jane J. Yu & Erik Zhang & Yoshihiro Hasegawa & John G. Noel & Jason C. Gardner & Elizabeth J. K, 2023. "Insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    13. J. McClatchy & R. Strogantsev & E. Wolfe & H. Y. Lin & M. Mohammadhosseini & B. A. Davis & C. Eden & D. Goldman & W. H. Fleming & P. Conley & G. Wu & L. Cimmino & H. Mohammed & A. Agarwal, 2023. "Clonal hematopoiesis related TET2 loss-of-function impedes IL1β-mediated epigenetic reprogramming in hematopoietic stem and progenitor cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    14. Ci Fu & Xiang Zhang & Amanda O. Veri & Kali R. Iyer & Emma Lash & Alice Xue & Huijuan Yan & Nicole M. Revie & Cassandra Wong & Zhen-Yuan Lin & Elizabeth J. Polvi & Sean D. Liston & Benjamin VanderSlui, 2021. "Leveraging machine learning essentiality predictions and chemogenomic interactions to identify antifungal targets," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    15. Junyi Chen & Xiaoying Wang & Anjun Ma & Qi-En Wang & Bingqiang Liu & Lang Li & Dong Xu & Qin Ma, 2022. "Deep transfer learning of cancer drug responses by integrating bulk and single-cell RNA-seq data," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    16. Kotaro Shimizu & Junichi Kikuta & Yumi Ohta & Yutaka Uchida & Yu Miyamoto & Akito Morimoto & Shinya Yari & Takashi Sato & Takefumi Kamakura & Kazuo Oshima & Ryusuke Imai & Yu-Chen Liu & Daisuke Okuzak, 2023. "Single-cell transcriptomics of human cholesteatoma identifies an activin A-producing osteoclastogenic fibroblast subset inducing bone destruction," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    17. Young Hee Lee & Yu-Been Kim & Kyu Sik Kim & Mirae Jang & Ha Young Song & Sang-Ho Jung & Dong-Soo Ha & Joon Seok Park & Jaegeon Lee & Kyung Min Kim & Deok-Hyeon Cheon & Inhyeok Baek & Min-Gi Shin & Eun, 2023. "Lateral hypothalamic leptin receptor neurons drive hunger-gated food-seeking and consummatory behaviours in male mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    18. Sandra Curras-Alonso & Juliette Soulier & Thomas Defard & Christian Weber & Sophie Heinrich & Hugo Laporte & Sophie Leboucher & Sonia Lameiras & Marie Dutreix & Vincent Favaudon & Florian Massip & Tho, 2023. "An interactive murine single-cell atlas of the lung responses to radiation injury," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    19. Seung-Hyun Jung & Byung-Hee Hwang & Sun Shin & Eun-Hye Park & Sin-Hee Park & Chan Woo Kim & Eunmin Kim & Eunho Choo & Ik Jun Choi & Filip K. Swirski & Kiyuk Chang & Yeun-Jun Chung, 2022. "Spatiotemporal dynamics of macrophage heterogeneity and a potential function of Trem2hi macrophages in infarcted hearts," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    20. Hailun Zhu & Sihai Dave Zhao & Alokananda Ray & Yu Zhang & Xin Li, 2022. "A comprehensive temporal patterning gene network in Drosophila medulla neuroblasts revealed by single-cell RNA sequencing," Nature Communications, Nature, vol. 13(1), pages 1-19, 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:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35938-x. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.