IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-30557-4.html
   My bibliography  Save this article

Robust temporal map of human in vitro myelopoiesis using single-cell genomics

Author

Listed:
  • Clara Alsinet

    (Wellcome Genome Campus
    Wellcome Genome Campus)

  • Maria Nascimento Primo

    (Wellcome Genome Campus
    Wellcome Genome Campus)

  • Valentina Lorenzi

    (Wellcome Genome Campus)

  • Erica Bello

    (Wellcome Genome Campus
    Wellcome Genome Campus)

  • Iva Kelava

    (Wellcome Genome Campus)

  • Carla P. Jones

    (Wellcome Genome Campus)

  • Roser Vilarrasa-Blasi

    (Wellcome Genome Campus)

  • Carmen Sancho-Serra

    (Wellcome Genome Campus)

  • Andrew J. Knights

    (Wellcome Genome Campus)

  • Jong-Eun Park

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Beata S. Wyspianska

    (Wellcome Genome Campus
    Medicines Research Centre, GlaxoSmithKline)

  • Gosia Trynka

    (Wellcome Genome Campus
    Wellcome Genome Campus)

  • David F. Tough

    (Medicines Research Centre, GlaxoSmithKline)

  • Andrew Bassett

    (Wellcome Genome Campus
    Wellcome Genome Campus)

  • Daniel J. Gaffney

    (Wellcome Genome Campus)

  • Damiana Alvarez-Errico

    (Josep Carreras Leukaemia Research Institute (IJC))

  • Roser Vento-Tormo

    (Wellcome Genome Campus)

Abstract

Myeloid cells are central to homeostasis and immunity. Characterising in vitro myelopoiesis protocols is imperative for their use in research, immunotherapies, and understanding human myelopoiesis. Here, we generate a >470K cells molecular map of human induced pluripotent stem cells (iPSC) differentiation into macrophages. Integration with in vivo single-cell atlases shows in vitro differentiation recapitulates features of yolk sac hematopoiesis, before definitive hematopoietic stem cells (HSC) emerge. The diversity of myeloid cells generated, including mast cells and monocytes, suggests that HSC-independent hematopoiesis can produce multiple myeloid lineages. We uncover poorly described myeloid progenitors and conservation between in vivo and in vitro regulatory programs. Additionally, we develop a protocol to produce iPSC-derived dendritic cells (DC) resembling cDC2. Using CRISPR/Cas9 knock-outs, we validate the effects of key transcription factors in macrophage and DC ontogeny. This roadmap of myeloid differentiation is an important resource for investigating human fetal hematopoiesis and new therapeutic opportunities.

Suggested Citation

  • Clara Alsinet & Maria Nascimento Primo & Valentina Lorenzi & Erica Bello & Iva Kelava & Carla P. Jones & Roser Vilarrasa-Blasi & Carmen Sancho-Serra & Andrew J. Knights & Jong-Eun Park & Beata S. Wysp, 2022. "Robust temporal map of human in vitro myelopoiesis using single-cell genomics," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30557-4
    DOI: 10.1038/s41467-022-30557-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-30557-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-30557-4?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. Mercedes Ricote & Andrew C. Li & Timothy M. Willson & Carolyn J. Kelly & Christopher K. Glass, 1998. "The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation," Nature, Nature, vol. 391(6662), pages 79-82, January.
    2. Dorin-Mirel Popescu & Rachel A. Botting & Emily Stephenson & Kile Green & Simone Webb & Laura Jardine & Emily F. Calderbank & Krzysztof Polanski & Issac Goh & Mirjana Efremova & Meghan Acres & Daniel , 2019. "Decoding human fetal liver haematopoiesis," Nature, Nature, vol. 574(7778), pages 365-371, October.
    3. Tsing-Lee Tang-Huau & Paul Gueguen & Christel Goudot & Mélanie Durand & Mylène Bohec & Sylvain Baulande & Benoit Pasquier & Sebastian Amigorena & Elodie Segura, 2018. "Human in vivo-generated monocyte-derived dendritic cells and macrophages cross-present antigens through a vacuolar pathway," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    4. Zhilei Bian & Yandong Gong & Tao Huang & Christopher Z. W. Lee & Lihong Bian & Zhijie Bai & Hui Shi & Yang Zeng & Chen Liu & Jian He & Jie Zhou & Xianlong Li & Zongcheng Li & Yanli Ni & Chunyu Ma & Le, 2020. "Deciphering human macrophage development at single-cell resolution," Nature, Nature, vol. 582(7813), pages 571-576, June.
    5. Roser Vento-Tormo & Mirjana Efremova & Rachel A. Botting & Margherita Y. Turco & Miquel Vento-Tormo & Kerstin B. Meyer & Jong-Eun Park & Emily Stephenson & Krzysztof Polański & Angela Goncalves & Lucy, 2018. "Single-cell reconstruction of the early maternal–fetal interface in humans," Nature, Nature, vol. 563(7731), pages 347-353, November.
    6. Baolin Liu & Chenwei Li & Ziyi Li & Dongfang Wang & Xianwen Ren & Zemin Zhang, 2020. "An entropy-based metric for assessing the purity of single cell populations," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    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. Jake R. Thomas & Anna Appios & Emily F. Calderbank & Nagisa Yoshida & Xiaohui Zhao & Russell S. Hamilton & Ashley Moffett & Andrew Sharkey & Elisa Laurenti & Courtney W. Hanna & Naomi McGovern, 2023. "Primitive haematopoiesis in the human placenta gives rise to macrophages with epigenetically silenced HLA-DR," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Hanbing Song & Simon Bucher & Katherine Rosenberg & Margaret Tsui & Deviana Burhan & Daniel Hoffman & Soo-Jin Cho & Arun Rangaswami & Marcus Breese & Stanley Leung & María V. Pons Ventura & E. Alejand, 2022. "Single-cell analysis of hepatoblastoma identifies tumor signatures that predict chemotherapy susceptibility using patient-specific tumor spheroids," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Yanchuan Li & Huamei Li & Cheng Peng & Ge Meng & Yijun Lu & Honglin Liu & Li Cui & Huan Zhou & Zhu Xu & Lingyun Sun & Lihong Liu & Qing Xiong & Beicheng Sun & Shiping Jiao, 2024. "Unraveling the spatial organization and development of human thymocytes through integration of spatial transcriptomics and single-cell multi-omics profiling," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    4. Lichun Ma & Sophia Heinrich & Limin Wang & Friederike L. Keggenhoff & Subreen Khatib & Marshonna Forgues & Michael Kelly & Stephen M. Hewitt & Areeba Saif & Jonathan M. Hernandez & Donna Mabry & Roman, 2022. "Multiregional single-cell dissection of tumor and immune cells reveals stable lock-and-key features in liver cancer," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Agnieska Brazovskaja & Tomás Gomes & Rene Holtackers & Philipp Wahle & Christiane Körner & Zhisong He & Theresa Schaffer & Julian Connor Eckel & René Hänsel & Malgorzata Santel & Makiko Seimiya & Timm, 2024. "Cell atlas of the regenerating human liver after portal vein embolization," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    6. 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.
    7. Jeff DeMartino & Michael T. Meister & Lindy L. Visser & Mariël Brok & Marian J. A. Groot Koerkamp & Amber K. L. Wezenaar & Laura S. Hiemcke-Jiwa & Terezinha Souza & Johannes H. M. Merks & Anne C. Rios, 2023. "Single-cell transcriptomics reveals immune suppression and cell states predictive of patient outcomes in rhabdomyosarcoma," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Qian-Yue Zhang & Xiao-Ping Ye & Zheng Zhou & Chen-Fang Zhu & Rui Li & Ya Fang & Rui-Jia Zhang & Lu Li & Wei Liu & Zheng Wang & Shi-Yang Song & Sang-Yu Lu & Shuang-Xia Zhao & Jian-Nan Lin & Huai-Dong S, 2022. "Lymphocyte infiltration and thyrocyte destruction are driven by stromal and immune cell components in Hashimoto’s thyroiditis," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    9. Du Wenqiang & Ashkan Novin & Yamin Liu & Junaid Afzal & Yasir Suhail & Shaofei Liu & Nicole R. Gavin & Jennifer R. Jorgensen & Christopher M. Morosky & Reinaldo Figueroa & Tannin A. Schmidt & Melinda , 2024. "Scar matrix drives Piezo1 mediated stromal inflammation leading to placenta accreta spectrum," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    10. Erica Carolina & Yoshiki Kuse & Ayumu Okumura & Kenji Aoshima & Tomomi Tadokoro & Shinya Matsumoto & Eriko Kanai & Takashi Okumura & Toshiharu Kasai & Souichiro Yamabe & Yuji Nishikawa & Kiyoshi Yamag, 2024. "Generation of human iPSC-derived 3D bile duct within liver organoid by incorporating human iPSC-derived blood vessel," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    11. Xi Li & Alfonso Poire & Kang Jin Jeong & Dong Zhang & Tugba Yildiran Ozmen & Gang Chen & Chaoyang Sun & Gordon B. Mills, 2024. "C5aR1 inhibition reprograms tumor associated macrophages and reverses PARP inhibitor resistance in breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    12. Akimichi Inaba & Zewen Kelvin Tuong & Tian X. Zhao & Andrew P. Stewart & Rebeccah Mathews & Lucy Truman & Rouchelle Sriranjan & Jane Kennet & Kourosh Saeb-Parsy & Linda Wicker & Frank Waldron-Lynch & , 2023. "Low-dose IL-2 enhances the generation of IL-10-producing immunoregulatory B cells," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    13. Ondrej Suchanek & John R. Ferdinand & Zewen K. Tuong & Sathi Wijeyesinghe & Anita Chandra & Ann-Katrin Clauder & Larissa N. Almeida & Simon Clare & Katherine Harcourt & Christopher J. Ward & Rachael B, 2023. "Tissue-resident B cells orchestrate macrophage polarisation and function," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    14. Meng Liu & Mengjun Ji & Jianghong Cheng & Yingzhe Li & Yingpu Tian & Hui Zhao & Yang Wang & Sijing Zhu & Leilei Zhang & Xinmei Xu & Gen-Sheng Feng & Xiaohuan Liang & Haili Bao & Yedong Tang & Shuangbo, 2023. "Deciphering a critical role of uterine epithelial SHP2 in parturition initiation at single cell resolution," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    15. Adele M. Alchahin & Shenglin Mei & Ioanna Tsea & Taghreed Hirz & Youmna Kfoury & Douglas Dahl & Chin-Lee Wu & Alexander O. Subtelny & Shulin Wu & David T. Scadden & John H. Shin & Philip J. Saylor & D, 2022. "A transcriptional metastatic signature predicts survival in clear cell renal cell carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    16. Zhongwei Xin & Mingjie Lin & Zhixing Hao & Di Chen & Yongyuan Chen & Xiaoke Chen & Xia Xu & Jinfan Li & Dang Wu & Ying Chai & Pin Wu, 2022. "The immune landscape of human thymic epithelial tumors," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    17. Tiffany Tate & Tina Xiang & Sarah E. Wobker & Mi Zhou & Xiao Chen & Hyunwoo Kim & Ekatherina Batourina & Chyuan-Sheng Lin & William Y. Kim & Chao Lu & James M. Mckiernan & Cathy Lee Mendelsohn, 2021. "Pparg signaling controls bladder cancer subtype and immune exclusion," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    18. David R. Ghasemi & Konstantin Okonechnikov & Anne Rademacher & Stephan Tirier & Kendra K. Maass & Hanna Schumacher & Piyush Joshi & Maxwell P. Gold & Julia Sundheimer & Britta Statz & Ahmet S. Rifaiog, 2024. "Compartments in medulloblastoma with extensive nodularity are connected through differentiation along the granular precursor lineage," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    19. F. Nadalin & M. J. Marzi & M. Pirra Piscazzi & P. Fuentes-Bravo & S. Procaccia & M. Climent & P. Bonetti & C. Rubolino & B. Giuliani & I. Papatheodorou & J. C. Marioni & F. Nicassio, 2024. "Multi-omic lineage tracing predicts the transcriptional, epigenetic and genetic determinants of cancer evolution," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    20. Matthew A. Cottam & Heather L. Caslin & Nathan C. Winn & Alyssa H. Hasty, 2022. "Multiomics reveals persistence of obesity-associated immune cell phenotypes in adipose tissue during weight loss and weight regain in mice," Nature Communications, Nature, vol. 13(1), pages 1-16, 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_s41467-022-30557-4. 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.