IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-38001-x.html
   My bibliography  Save this article

RNA binding protein SYNCRIP maintains proteostasis and self-renewal of hematopoietic stem and progenitor cells

Author

Listed:
  • Florisela Herrejon Chavez

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Hanzhi Luo

    (Memorial Sloan Kettering Cancer Center)

  • Paolo Cifani

    (Memorial Sloan Kettering Cancer Center
    Cold Spring Harbor Laboratory)

  • Alli Pine

    (Memorial Sloan Kettering Cancer Center)

  • Karen L. Chu

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell School of Medical Sciences)

  • Suhasini Joshi

    (Memorial Sloan Kettering Cancer Center)

  • Ersilia Barin

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center
    Pharmacology Program of the Weill Cornell Graduate School of Medicine Sciences)

  • Alexandra Schurer

    (Memorial Sloan Kettering Cancer Center)

  • Mandy Chan

    (Memorial Sloan Kettering Cancer Center)

  • Kathryn Chang

    (Memorial Sloan Kettering Cancer Center)

  • Grace Y. Q. Han

    (Memorial Sloan Kettering Cancer Center)

  • Aspen J. Pierson

    (Memorial Sloan Kettering Cancer Center)

  • Michael Xiao

    (Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program)

  • Xuejing Yang

    (Memorial Sloan Kettering Cancer Center)

  • Lindsey M. Kuehm

    (Cell Microsystems, Inc.)

  • Yuning Hong

    (La Trobe Institute for Molecular Science, La Trobe University)

  • Diu T. T. Nguyen

    (Memorial Sloan Kettering Cancer Center
    Barts Cancer Institute, Queen Mary University of London)

  • Gabriela Chiosis

    (Memorial Sloan Kettering Cancer Center)

  • Alex Kentsis

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center
    Weill Medical College of Cornell University)

  • Christina Leslie

    (Memorial Sloan Kettering Cancer Center)

  • Ly P. Vu

    (Memorial Sloan Kettering Cancer Center
    British Columbia Cancer Research Centre
    University of British Columbia)

  • Michael G. Kharas

    (Memorial Sloan Kettering Cancer Center)

Abstract

Tissue homeostasis is maintained after stress by engaging and activating the hematopoietic stem and progenitor compartments in the blood. Hematopoietic stem cells (HSCs) are essential for long-term repopulation after secondary transplantation. Here, using a conditional knockout mouse model, we revealed that the RNA-binding protein SYNCRIP is required for maintenance of blood homeostasis especially after regenerative stress due to defects in HSCs and progenitors. Mechanistically, we find that SYNCRIP loss results in a failure to maintain proteome homeostasis that is essential for HSC maintenance. SYNCRIP depletion results in increased protein synthesis, a dysregulated epichaperome, an accumulation of misfolded proteins and induces endoplasmic reticulum stress. Additionally, we find that SYNCRIP is required for translation of CDC42 RHO-GTPase, and loss of SYNCRIP results in defects in polarity, asymmetric segregation, and dilution of unfolded proteins. Forced expression of CDC42 recovers polarity and in vitro replating activities of HSCs. Taken together, we uncovered a post-transcriptional regulatory program that safeguards HSC self-renewal capacity and blood homeostasis.

Suggested Citation

  • Florisela Herrejon Chavez & Hanzhi Luo & Paolo Cifani & Alli Pine & Karen L. Chu & Suhasini Joshi & Ersilia Barin & Alexandra Schurer & Mandy Chan & Kathryn Chang & Grace Y. Q. Han & Aspen J. Pierson , 2023. "RNA binding protein SYNCRIP maintains proteostasis and self-renewal of hematopoietic stem and progenitor cells," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38001-x
    DOI: 10.1038/s41467-023-38001-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-38001-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-38001-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. Alejo E. Rodriguez-Fraticelli & Caleb Weinreb & Shou-Wen Wang & Rosa P. Migueles & Maja Jankovic & Marc Usart & Allon M. Klein & Sally Lowell & Fernando D. Camargo, 2020. "Single-cell lineage tracing unveils a role for TCF15 in haematopoiesis," Nature, Nature, vol. 583(7817), pages 585-589, July.
    2. Shuxian Dong & Qian Wang & Yun-Ruei Kao & Antonio Diaz & Inmaculada Tasset & Susmita Kaushik & Victor Thiruthuvanathan & Aliona Zintiridou & Edward Nieves & Monika Dzieciatkowska & Julie A. Reisz & Ev, 2021. "Chaperone-mediated autophagy sustains haematopoietic stem-cell function," Nature, Nature, vol. 591(7848), pages 117-123, March.
    3. Moore Z. Chen & Nagaraj S. Moily & Jessica L. Bridgford & Rebecca J. Wood & Mona Radwan & Trevor A. Smith & Zhegang Song & Ben Zhong Tang & Leann Tilley & Xiaohong Xu & Gavin E. Reid & Mahmoud A. Poul, 2017. "A thiol probe for measuring unfolded protein load and proteostasis in cells," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    4. Anna Rodina & Tai Wang & Pengrong Yan & Erica DaGama Gomes & Mark P. S. Dunphy & Nagavarakishore Pillarsetty & John Koren & John F. Gerecitano & Tony Taldone & Hongliang Zong & Eloisi Caldas-Lopes & M, 2016. "The epichaperome is an integrated chaperome network that facilitates tumour survival," Nature, Nature, vol. 538(7625), pages 397-401, October.
    5. Peter van Galen & Antonija Kreso & Nathan Mbong & David G. Kent & Timothy Fitzmaurice & Joseph E. Chambers & Stephanie Xie & Elisa Laurenti & Karin Hermans & Kolja Eppert & Stefan J. Marciniak & Jane , 2014. "The unfolded protein response governs integrity of the haematopoietic stem-cell pool during stress," Nature, Nature, vol. 510(7504), pages 268-272, June.
    6. Matthew R. Warr & Mikhail Binnewies & Johanna Flach & Damien Reynaud & Trit Garg & Ritu Malhotra & Jayanta Debnath & Emmanuelle Passegué, 2013. "FOXO3A directs a protective autophagy program in haematopoietic stem cells," Nature, Nature, vol. 494(7437), pages 323-327, February.
    7. Robert A. J. Signer & Jeffrey A. Magee & Adrian Salic & Sean J. Morrison, 2014. "Haematopoietic stem cells require a highly regulated protein synthesis rate," Nature, Nature, vol. 509(7498), pages 49-54, May.
    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. Narasaiah Kovuru & Makiko Mochizuki-Kashio & Theresa Menna & Greer Jeffrey & Yuning Hong & Young me Yoon & Zhe Zhang & Peter Kurre, 2024. "Deregulated protein homeostasis constrains fetal hematopoietic stem cell pool expansion in Fanconi anemia," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Kim Vanuytsel & Carlos Villacorta-Martin & Jonathan Lindstrom-Vautrin & Zhe Wang & Wilfredo F. Garcia-Beltran & Vladimir Vrbanac & Dylan Parsons & Evan C. Lam & Taylor M. Matte & Todd W. Dowrey & Sara, 2022. "Multi-modal profiling of human fetal liver hematopoietic stem cells reveals the molecular signature of engraftment," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Humberto Contreras-Trujillo & Jiya Eerdeng & Samir Akre & Du Jiang & Jorge Contreras & Basia Gala & Mary C. Vergel-Rodriguez & Yeachan Lee & Aparna Jorapur & Areen Andreasian & Lisa Harton & Charles S, 2021. "Deciphering intratumoral heterogeneity using integrated clonal tracking and single-cell transcriptome analyses," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    4. Pekka Jaako & Alexandre Faille & Shengjiang Tan & Chi C. Wong & Norberto Escudero-Urquijo & Pablo Castro-Hartmann & Penny Wright & Christine Hilcenko & David J. Adams & Alan J. Warren, 2022. "eIF6 rebinding dynamically couples ribosome maturation and translation," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    5. Zijian Fang & Giuditta Corbizi Fattori & Thomas McKerrell & Rebecca H. Boucher & Aimee Jackson & Rachel S. Fletcher & Dorian Forte & Jose-Ezequiel Martin & Sonia Fox & James Roberts & Rachel Glover & , 2023. "Tamoxifen for the treatment of myeloproliferative neoplasms: A Phase II clinical trial and exploratory analysis," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    6. Dezerae Cox & Ching-Seng Ang & Nadinath B. Nillegoda & Gavin E. Reid & Danny M. Hatters, 2022. "Hidden information on protein function in censuses of proteome foldedness," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    7. Yumin Liu & Linjuan Shi & Yifan Chen & Sifan Luo & Yuehang Chen & Hongtian Chen & Wenlang Lan & Xun Lu & Zhan Cao & Zehua Ye & Jinping Li & Bo Yu & Elaine Dzierzak & Zhuan Li, 2024. "Autophagy regulates the maturation of hematopoietic precursors in the embryo," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    8. Anna Rodina & Chao Xu & Chander S. Digwal & Suhasini Joshi & Yogita Patel & Anand R. Santhaseela & Sadik Bay & Swathi Merugu & Aftab Alam & Pengrong Yan & Chenghua Yang & Tanaya Roychowdhury & Palak P, 2023. "Systems-level analyses of protein-protein interaction network dysfunctions via epichaperomics identify cancer-specific mechanisms of stress adaptation," Nature Communications, Nature, vol. 14(1), pages 1-26, December.
    9. Kaushik Bhattacharya & Samarpan Maiti & Szabolcs Zahoran & Lorenz Weidenauer & Dina Hany & Diana Wider & Lilia Bernasconi & Manfredo Quadroni & Martine Collart & Didier Picard, 2022. "Translational reprogramming in response to accumulating stressors ensures critical threshold levels of Hsp90 for mammalian life," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    10. Kyung Mok Kim & Anna Mura-Meszaros & Marie Tollot & Murali Shyam Krishnan & Marco Gründl & Laura Neubert & Marco Groth & Alejo Rodriguez-Fraticelli & Arthur Flohr Svendsen & Stefano Campaner & Nico An, 2022. "Taz protects hematopoietic stem cells from an aging-dependent decrease in PU.1 activity," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    11. A. S. Eisele & M. Tarbier & A. A. Dormann & V. Pelechano & D. M. Suter, 2024. "Gene-expression memory-based prediction of cell lineages from scRNA-seq datasets," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    12. WeiChao Hao & MeiJuan Dian & Ying Zhou & QiuLing Zhong & WenQian Pang & ZiJian Li & YaYan Zhao & JiaCheng Ma & XiaoLin Lin & RenRu Luo & YongLong Li & JunShuang Jia & HongFen Shen & ShiHao Huang & Gua, 2022. "Autophagy induction promoted by m6A reader YTHDF3 through translation upregulation of FOXO3 mRNA," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    13. Jacqueline Feyen & Zhen Ping & Lanpeng Chen & Claire Dijk & Tim V. D. Tienhoven & Paulina M. H. Strien & Remco M. Hoogenboezem & Michiel J. W. Wevers & Mathijs A. Sanders & Ivo P. Touw & Marc H. G. P., 2022. "Myeloid cells promote interferon signaling-associated deterioration of the hematopoietic system," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    14. Hannah Drew Rickner & Lulu Jiang & Rui Hong & Nicholas K. O’Neill & Chromewell A. Mojica & Benjamin J. Snyder & Lushuang Zhang & Dipan Shaw & Maria Medalla & Benjamin Wolozin & Christine S. Cheng, 2022. "Single cell transcriptomic profiling of a neuron-astrocyte assembloid tauopathy model," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    15. Mina N. F. Morcos & Congxin Li & Clara M. Munz & Alessandro Greco & Nicole Dressel & Susanne Reinhardt & Katrin Sameith & Andreas Dahl & Nils B. Becker & Axel Roers & Thomas Höfer & Alexander Gerbaule, 2022. "Fate mapping of hematopoietic stem cells reveals two pathways of native thrombopoiesis," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    16. Mark R. Woodford & Dimitra Bourboulia & Mehdi Mollapour, 2023. "Epichaperomics reveals dysfunctional chaperone protein networks," Nature Communications, Nature, vol. 14(1), pages 1-3, December.
    17. Naomi R. Genuth & Zhen Shi & Koshi Kunimoto & Victoria Hung & Adele F. Xu & Craig H. Kerr & Gerald C. Tiu & Juan A. Oses-Prieto & Rachel E. A. Salomon-Shulman & Jeffrey D. Axelrod & Alma L. Burlingame, 2022. "A stem cell roadmap of ribosome heterogeneity reveals a function for RPL10A in mesoderm production," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    18. Jos Urbanus & Jason Cosgrove & Joost B. Beltman & Yuval Elhanati & Rafael A. Moral & Cecile Conrad & Jeroen W. Heijst & Emilie Tubeuf & Arno Velds & Lianne Kok & Candice Merle & Jens P. Magnusson & Lé, 2023. "DRAG in situ barcoding reveals an increased number of HSPCs contributing to myelopoiesis with age," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    19. Joana Silva & Ferhat Alkan & Sofia Ramalho & Goda Snieckute & Stefan Prekovic & Ana Krotenberg Garcia & Santiago Hernández-Pérez & Rob Kammen & Danielle Barnum & Liesbeth Hoekman & Maarten Altelaar & , 2022. "Ribosome impairment regulates intestinal stem cell identity via ZAKɑ activation," Nature Communications, Nature, vol. 13(1), pages 1-12, 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_s41467-023-38001-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.