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IκBα controls dormancy in hematopoietic stem cells via retinoic acid during embryonic development

Author

Listed:
  • Roshana Thambyrajah

    (Hospital del Mar Research Institute
    Josep Carreras Leukemia Research Institute)

  • Maria Maqueda

    (Hospital del Mar Research Institute
    Josep Carreras Leukemia Research Institute
    Centro de Investigacion Biomedica en Red Cancer (CIBERONC))

  • Muhammad Zaki Fadlullah

    (The University of Manchester)

  • Martin Proffitt

    (Hospital del Mar Research Institute)

  • Wen Hao Neo

    (The University of Manchester)

  • Yolanda Guillén

    (Hospital del Mar Research Institute)

  • Marta Casado-Pelaez

    (Josep Carreras Leukemia Research Institute)

  • Patricia Herrero-Molinero

    (Hospital del Mar Research Institute)

  • Carla Brujas

    (Hospital del Mar Research Institute)

  • Noemi Castelluccio

    (Hospital del Mar Research Institute
    Ghent University Hospital)

  • Jessica González

    (Hospital del Mar Research Institute
    Josep Carreras Leukemia Research Institute
    Centro de Investigacion Biomedica en Red Cancer (CIBERONC))

  • Arnau Iglesias

    (Hospital del Mar Research Institute
    Josep Carreras Leukemia Research Institute
    Centro de Investigacion Biomedica en Red Cancer (CIBERONC))

  • Laura Marruecos

    (Hospital del Mar Research Institute)

  • Cristina Ruiz-Herguido

    (Hospital del Mar Research Institute)

  • Manel Esteller

    (Josep Carreras Leukemia Research Institute
    Centro de Investigacion Biomedica en Red Cancer (CIBERONC)
    Institucio Catalana de Recerca i Estudis Avançats (ICREA)
    University of Barcelona (UB))

  • Elisabetta Mereu

    (Josep Carreras Leukemia Research Institute)

  • Georges Lacaud

    (The University of Manchester)

  • Lluis Espinosa

    (Hospital del Mar Research Institute
    Centro de Investigacion Biomedica en Red Cancer (CIBERONC))

  • Anna Bigas

    (Hospital del Mar Research Institute
    Josep Carreras Leukemia Research Institute
    Centro de Investigacion Biomedica en Red Cancer (CIBERONC))

Abstract

Recent findings suggest that Hematopoietic Stem Cells (HSC) and progenitors arise simultaneously and independently of each other already in the embryonic aorta-gonad mesonephros region, but it is still unknown how their different features are established. Here, we uncover IκBα (Nfkbia, the inhibitor of NF-κB) as a critical regulator of HSC proliferation throughout development. IκBα balances retinoic acid signaling levels together with the epigenetic silencer, PRC2, specifically in HSCs. Loss of IκBα decreases proliferation of HSC and induces a dormancy related gene expression signature instead. Also, IκBα deficient HSCs respond with superior activation to in vitro culture and in serial transplantation. At the molecular level, chromatin regions harboring binding motifs for retinoic acid signaling are hypo-methylated for the PRC2 dependent H3K27me3 mark in IκBα deficient HSCs. Overall, we show that the proliferation index in the developing HSCs is regulated by a IκBα-PRC2 axis, which controls retinoic acid signaling.

Suggested Citation

  • Roshana Thambyrajah & Maria Maqueda & Muhammad Zaki Fadlullah & Martin Proffitt & Wen Hao Neo & Yolanda Guillén & Marta Casado-Pelaez & Patricia Herrero-Molinero & Carla Brujas & Noemi Castelluccio & , 2024. "IκBα controls dormancy in hematopoietic stem cells via retinoic acid during embryonic development," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48854-5
    DOI: 10.1038/s41467-024-48854-5
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    References listed on IDEAS

    as
    1. Sachin H. Patel & Constantina Christodoulou & Caleb Weinreb & Qi Yu & Edroaldo Lummertz da Rocha & Brian J. Pepe-Mooney & Sarah Bowling & Li Li & Fernando G. Osorio & George Q. Daley & Fernando D. Cam, 2022. "Lifelong multilineage contribution by embryonic-born blood progenitors," Nature, Nature, vol. 606(7915), pages 747-753, June.
    2. Roshana Thambyrajah & Maria Maqueda & Wen Hao Neo & Kathleen Imbach & Yolanda Guillén & Daniela Grases & Zaki Fadlullah & Stefano Gambera & Francesca Matteini & Xiaonan Wang & Fernando J. Calero-Nieto, 2024. "Cis inhibition of NOTCH1 through JAGGED1 sustains embryonic hematopoietic stem cell fate," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Tomomasa Yokomizo & Takako Ideue & Saori Morino-Koga & Cheng Yong Tham & Tomohiko Sato & Naoki Takeda & Yoshiaki Kubota & Mineo Kurokawa & Norio Komatsu & Minetaro Ogawa & Kimi Araki & Motomi Osato & , 2022. "Independent origins of fetal liver haematopoietic stem and progenitor cells," Nature, Nature, vol. 609(7928), pages 779-784, September.
    4. Alejo E. Rodriguez-Fraticelli & Samuel L. Wolock & Caleb S. Weinreb & Riccardo Panero & Sachin H. Patel & Maja Jankovic & Jianlong Sun & Raffaele A. Calogero & Allon M. Klein & Fernando D. Camargo, 2018. "Clonal analysis of lineage fate in native haematopoiesis," Nature, Nature, vol. 553(7687), pages 212-216, January.
    5. Fan Zhou & Xianlong Li & Weili Wang & Ping Zhu & Jie Zhou & Wenyan He & Meng Ding & Fuyin Xiong & Xiaona Zheng & Zhuan Li & Yanli Ni & Xiaohuan Mu & Lu Wen & Tao Cheng & Yu Lan & Weiping Yuan & Fuchou, 2016. "Tracing haematopoietic stem cell formation at single-cell resolution," Nature, Nature, vol. 533(7604), pages 487-492, May.
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