IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-28781-z.html
   My bibliography  Save this article

Engineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics

Author

Listed:
  • Brandon Hadland

    (Clinical Research Division, Fred Hutchinson Cancer Research Center
    University of Washington School of Medicine)

  • Barbara Varnum-Finney

    (Clinical Research Division, Fred Hutchinson Cancer Research Center)

  • Stacey Dozono

    (Clinical Research Division, Fred Hutchinson Cancer Research Center)

  • Tessa Dignum

    (Clinical Research Division, Fred Hutchinson Cancer Research Center)

  • Cynthia Nourigat-McKay

    (Clinical Research Division, Fred Hutchinson Cancer Research Center)

  • Adam M. Heck

    (Clinical Research Division, Fred Hutchinson Cancer Research Center)

  • Takashi Ishida

    (Clinical Research Division, Fred Hutchinson Cancer Research Center)

  • Dana L. Jackson

    (University of Washington School of Medicine)

  • Tomer Itkin

    (Department of Genetic Medicine, Ansary Stem Cell Institute, Howard Hughes Medical Institute, Weill Cornell Medical College)

  • Jason M. Butler

    (Hackensack University Medical Center)

  • Shahin Rafii

    (Department of Genetic Medicine, Ansary Stem Cell Institute, Howard Hughes Medical Institute, Weill Cornell Medical College)

  • Cole Trapnell

    (University of Washington School of Medicine)

  • Irwin D. Bernstein

    (Clinical Research Division, Fred Hutchinson Cancer Research Center
    University of Washington School of Medicine)

Abstract

Hematopoietic stem cells (HSCs) develop from hemogenic endothelium within embryonic arterial vessels such as the aorta of the aorta-gonad-mesonephros region (AGM). To identify the signals responsible for HSC formation, here we use single cell RNA-sequencing to simultaneously analyze the transcriptional profiles of AGM-derived cells transitioning from hemogenic endothelium to HSCs, and AGM-derived endothelial cells which provide signals sufficient to support HSC maturation and self-renewal. Pseudotemporal ordering reveals dynamics of gene expression during the hemogenic endothelium to HSC transition, identifying surface receptors specifically expressed on developing HSCs. Transcriptional profiling of niche endothelial cells identifies corresponding ligands, including those signaling to Notch receptors, VLA-4 integrin, and CXCR4, which, when integrated in an engineered platform, are sufficient to support the generation of engrafting HSCs. These studies provide a transcriptional map of the signaling interactions necessary for the development of HSCs and advance the goal of engineering HSCs for therapeutic applications.

Suggested Citation

  • Brandon Hadland & Barbara Varnum-Finney & Stacey Dozono & Tessa Dignum & Cynthia Nourigat-McKay & Adam M. Heck & Takashi Ishida & Dana L. Jackson & Tomer Itkin & Jason M. Butler & Shahin Rafii & Cole , 2022. "Engineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28781-z
    DOI: 10.1038/s41467-022-28781-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-28781-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-28781-z?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. Leonor Gama-Norton & Eva Ferrando & Cristina Ruiz-Herguido & Zhenyi Liu & Jordi Guiu & Abul B. M. M. K. Islam & Sung-Uk Lee & Minhong Yan & Cynthia J. Guidos & Nuria López-Bigas & Takahiro Maeda & Llu, 2015. "Notch signal strength controls cell fate in the haemogenic endothelium," Nature Communications, Nature, vol. 6(1), pages 1-12, December.
    2. Phong Dang Nguyen & Georgina Elizabeth Hollway & Carmen Sonntag & Lee Barry Miles & Thomas Edward Hall & Silke Berger & Kristine Joy Fernandez & David Baruch Gurevich & Nicholas James Cole & Sara Alae, 2014. "Haematopoietic stem cell induction by somite-derived endothelial cells controlled by meox1," Nature, Nature, vol. 512(7514), pages 314-318, August.
    3. Jordan A. Ramilowski & Tatyana Goldberg & Jayson Harshbarger & Edda Kloppmann & Marina Lizio & Venkata P. Satagopam & Masayoshi Itoh & Hideya Kawaji & Piero Carninci & Burkhard Rost & Alistair R. R. F, 2015. "A draft network of ligand–receptor-mediated multicellular signalling in human," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    4. Vincenzo Calvanese & Andrew T. Nguyen & Timothy J. Bolan & Anastasia Vavilina & Trent Su & Lydia K. Lee & Yanling Wang & Fides D. Lay & Mattias Magnusson & Gay M. Crooks & Siavash K. Kurdistani & Hann, 2019. "MLLT3 governs human haematopoietic stem-cell self-renewal and engraftment," Nature, Nature, vol. 576(7786), pages 281-286, December.
    5. Chloé S. Baron & Lennart Kester & Anna Klaus & Jean-Charles Boisset & Roshana Thambyrajah & Laurent Yvernogeau & Valérie Kouskoff & Georges Lacaud & Alexander Oudenaarden & Catherine Robin, 2018. "Single-cell transcriptomics reveal the dynamic of haematopoietic stem cell production in the aorta," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    6. Melih Acar & Kiranmai S. Kocherlakota & Malea M. Murphy & James G. Peyer & Hideyuki Oguro & Christopher N. Inra & Christabel Jaiyeola & Zhiyu Zhao & Katherine Luby-Phelps & Sean J. Morrison, 2015. "Deep imaging of bone marrow shows non-dividing stem cells are mainly perisinusoidal," Nature, Nature, vol. 526(7571), pages 126-130, October.
    7. Morgan Oatley & Özge Vargel Bölükbası & Valentine Svensson & Maya Shvartsman & Kerstin Ganter & Katharina Zirngibl & Polina V. Pavlovich & Vladislava Milchevskaya & Vladimira Foteva & Kedar N. Nataraj, 2020. "Single-cell transcriptomics identifies CD44 as a marker and regulator of endothelial to haematopoietic transition," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    8. Joana Carrelha & Yiran Meng & Laura M. Kettyle & Tiago C. Luis & Ruggiero Norfo & Verónica Alcolea & Hanane Boukarabila & Francesca Grasso & Adriana Gambardella & Amit Grover & Kari Högstrand & Allegr, 2018. "Hierarchically related lineage-restricted fates of multipotent haematopoietic stem cells," Nature, Nature, vol. 554(7690), pages 106-111, February.
    9. Carlos O. Lizama & John S. Hawkins & Christopher E. Schmitt & Frank L. Bos & Joan P. Zape & Kelly M. Cautivo & Hugo Borges Pinto & Alexander M. Rhyner & Hui Yu & Mary E. Donohoe & Joshua D. Wythe & An, 2015. "Repression of arterial genes in hemogenic endothelium is sufficient for haematopoietic fate acquisition," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    10. Alejandra Sanjuan-Pla & Iain C. Macaulay & Christina T. Jensen & Petter S. Woll & Tiago C. Luis & Adam Mead & Susan Moore & Cintia Carella & Sahoko Matsuoka & Tiphaine Bouriez Jones & Onima Chowdhury , 2013. "Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy," Nature, Nature, vol. 502(7470), pages 232-236, October.
    11. Monica Corada & Fabrizio Orsenigo & Marco Francesco Morini & Mara Elena Pitulescu & Ganesh Bhat & Daniel Nyqvist & Ferruccio Breviario & Valentina Conti & Anais Briot & M. Luisa Iruela-Arispe & Ralf H, 2013. "Sox17 is indispensable for acquisition and maintenance of arterial identity," Nature Communications, Nature, vol. 4(1), pages 1-14, December.
    12. Céline Souilhol & Christèle Gonneau & Javier G. Lendinez & Antoniana Batsivari & Stanislav Rybtsov & Heather Wilson & Lucia Morgado-Palacin & David Hills & Samir Taoudi & Jennifer Antonchuk & Suling Z, 2016. "Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult haematopoietic stem cells," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    13. 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.
    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. Patrick Coulombe & Grace Cole & Amanda Fentiman & Jeremy D. K. Parker & Eric Yung & Misha Bilenky & Lemlem Degefie & Patrick Lac & Maggie Y. M. Ling & Derek Tam & R. Keith Humphries & Aly Karsan, 2023. "Meis1 establishes the pre-hemogenic endothelial state prior to Runx1 expression," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. 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.
    3. Tiago C. Luis & Nikolaos Barkas & Joana Carrelha & Alice Giustacchini & Stefania Mazzi & Ruggiero Norfo & Bishan Wu & Affaf Aliouat & Jose A. Guerrero & Alba Rodriguez-Meira & Tiphaine Bouriez-Jones &, 2023. "Perivascular niche cells sense thrombocytopenia and activate hematopoietic stem cells in an IL-1 dependent manner," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Yinghui Li & Mei He & Wenshan Zhang & Wei Liu & Hui Xu & Ming Yang & Hexiao Zhang & Haiwei Liang & Wenjing Li & Zhaozhao Wu & Weichao Fu & Shiqi Xu & Xiaolei Liu & Sibin Fan & Liwei Zhou & Chaoqun Wan, 2023. "Expansion of human megakaryocyte-biased hematopoietic stem cells by biomimetic Microniche," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Yang Liu & Qi Chen & Hyun-Woo Jeong & Bong Ihn Koh & Emma C. Watson & Cong Xu & Martin Stehling & Bin Zhou & Ralf H. Adams, 2022. "A specialized bone marrow microenvironment for fetal haematopoiesis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    6. Yan Tang & David J. Kwiatkowski & Elizabeth P. Henske, 2022. "Midkine expression by stem-like tumor cells drives persistence to mTOR inhibition and an immune-suppressive microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    7. Daniel Dimitrov & Dénes Türei & Martin Garrido-Rodriguez & Paul L. Burmedi & James S. Nagai & Charlotte Boys & Ricardo O. Ramirez Flores & Hyojin Kim & Bence Szalai & Ivan G. Costa & Alberto Valdeoliv, 2022. "Comparison of methods and resources for cell-cell communication inference from single-cell RNA-Seq data," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    8. 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.
    9. Raymond K. H. Yip & Joel S. Rimes & Bianca D. Capaldo & François Vaillant & Kellie A. Mouchemore & Bhupinder Pal & Yunshun Chen & Elliot Surgenor & Andrew J. Murphy & Robin L. Anderson & Gordon K. Smy, 2021. "Mammary tumour cells remodel the bone marrow vascular microenvironment to support metastasis," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    10. Aya Uchida & Kenya Imaimatsu & Honoka Suzuki & Xiao Han & Hiroki Ushioda & Mami Uemura & Kasane Imura-Kishi & Ryuji Hiramatsu & Hinako M. Takase & Yoshikazu Hirate & Atsuo Ogura & Masami Kanai-Azuma &, 2022. "SOX17-positive rete testis epithelium is required for Sertoli valve formation and normal spermiogenesis in the male mouse," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    11. Jonas Stewen & Kai Kruse & Anca T. Godoi-Filip & Zenia & Hyun-Woo Jeong & Susanne Adams & Frank Berkenfeld & Martin Stehling & Kristy Red-Horse & Ralf H. Adams & Mara E. Pitulescu, 2024. "Eph-ephrin signaling couples endothelial cell sorting and arterial specification," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    12. Kathryn Weinand & Saori Sakaue & Aparna Nathan & Anna Helena Jonsson & Fan Zhang & Gerald F. M. Watts & Majd Al Suqri & Zhu Zhu & Deepak A. Rao & Jennifer H. Anolik & Michael B. Brenner & Laura T. Don, 2024. "The chromatin landscape of pathogenic transcriptional cell states in rheumatoid arthritis," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    13. Taichi Nakatani & Tatsuki Sugiyama & Yoshiki Omatsu & Hitomi Watanabe & Gen Kondoh & Takashi Nagasawa, 2023. "Ebf3+ niche-derived CXCL12 is required for the localization and maintenance of hematopoietic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    14. Indranil Paul & Dante Bolzan & Ahmed Youssef & Keith A. Gagnon & Heather Hook & Gopal Karemore & Michael U. J. Oliphant & Weiwei Lin & Qian Liu & Sadhna Phanse & Carl White & Dzmitry Padhorny & Sergei, 2023. "Parallelized multidimensional analytic framework applied to mammary epithelial cells uncovers regulatory principles in EMT," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    15. Toshiyuki Ko & Seitaro Nomura & Shintaro Yamada & Kanna Fujita & Takanori Fujita & Masahiro Satoh & Chio Oka & Manami Katoh & Masamichi Ito & Mikako Katagiri & Tatsuro Sassa & Bo Zhang & Satoshi Hatsu, 2022. "Cardiac fibroblasts regulate the development of heart failure via Htra3-TGF-β-IGFBP7 axis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    16. Ziyang Tang & Zuotian Li & Tieying Hou & Tonglin Zhang & Baijian Yang & Jing Su & Qianqian Song, 2023. "SiGra: single-cell spatial elucidation through an image-augmented graph transformer," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    17. Young-Woong Kim & Greta Zara & HyunJun Kang & Sergio Branciamore & Denis O’Meally & Yuxin Feng & Chia-Yi Kuan & Yingjun Luo & Michael S. Nelson & Alex B. Brummer & Russell Rockne & Zhen Bouman Chen & , 2022. "Integration of single-cell transcriptomes and biological function reveals distinct behavioral patterns in bone marrow endothelium," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    18. Beibei Ru & Jinlin Huang & Yu Zhang & Kenneth Aldape & Peng Jiang, 2023. "Estimation of cell lineages in tumors from spatial transcriptomics data," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    19. Xia Chen & Peiliang Wang & Hui Qiu & Yonglin Zhu & Xingwu Zhang & Yaxuan Zhang & Fuyu Duan & Shuangyuan Ding & Jianying Guo & Yue Huang & Jie Na, 2022. "Integrative epigenomic and transcriptomic analysis reveals the requirement of JUNB for hematopoietic fate induction," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    20. Emi Murayama & Catherine Vivier & Anne Schmidt & Philippe Herbomel, 2023. "Alcam-a and Pdgfr-α are essential for the development of sclerotome-derived stromal cells that support hematopoiesis," Nature Communications, Nature, vol. 14(1), pages 1-17, 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:13:y:2022:i:1:d:10.1038_s41467-022-28781-z. 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.