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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
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    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    11. 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.
    12. 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.
    13. 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.
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