IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-48354-6.html
   My bibliography  Save this article

Direct conversion of cardiac fibroblasts into endothelial-like cells using Sox17 and Erg

Author

Listed:
  • Gregory Farber

    (The University of North Carolina at Chapel Hill)

  • Yanhan Dong

    (The University of North Carolina at Chapel Hill)

  • Qiaozi Wang

    (The University of North Carolina at Chapel Hill)

  • Mitesh Rathod

    (University of North Carolina at Chapel Hill and North Carolina State University
    University of North Carolina Kidney Center)

  • Haofei Wang

    (The University of North Carolina at Chapel Hill)

  • Michelle Dixit

    (The University of North Carolina at Chapel Hill)

  • Benjamin Keepers

    (The University of North Carolina at Chapel Hill
    The University of North Carolina at Chapel Hill)

  • Yifang Xie

    (The University of North Carolina at Chapel Hill)

  • Kendall Butz

    (The University of North Carolina at Chapel Hill)

  • William J. Polacheck

    (The University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill and North Carolina State University)

  • Jiandong Liu

    (The University of North Carolina at Chapel Hill
    The University of North Carolina at Chapel Hill)

  • Li Qian

    (The University of North Carolina at Chapel Hill
    The University of North Carolina at Chapel Hill)

Abstract

Endothelial cells are a heterogeneous population with various organ-specific and conserved functions that are critical to organ development, function, and regeneration. Here we report a Sox17-Erg direct reprogramming approach that uses cardiac fibroblasts to create differentiated endothelial cells that demonstrate endothelial-like molecular and physiological functions in vitro and in vivo. Injection of these induced endothelial cells into myocardial infarct sites after injury results in improved vascular perfusion of the scar region. Furthermore, we use genomic analyses to illustrate that Sox17-Erg reprogramming instructs cardiac fibroblasts toward an arterial-like identity. This results in a more efficient direct conversion of fibroblasts into endothelial-like cells when compared to traditional Etv2-based reprogramming. Overall, this Sox17-Erg direct reprogramming strategy offers a robust tool to generate endothelial cells both in vitro and in vivo, and has the potential to be used in repairing injured tissue.

Suggested Citation

  • Gregory Farber & Yanhan Dong & Qiaozi Wang & Mitesh Rathod & Haofei Wang & Michelle Dixit & Benjamin Keepers & Yifang Xie & Kendall Butz & William J. Polacheck & Jiandong Liu & Li Qian, 2024. "Direct conversion of cardiac fibroblasts into endothelial-like cells using Sox17 and Erg," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48354-6
    DOI: 10.1038/s41467-024-48354-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-48354-6
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-48354-6?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. Wen Luo & Irene Garcia-Gonzalez & Macarena Fernández-Chacón & Verónica Casquero-Garcia & Maria S. Sanchez-Muñoz & Severin Mühleder & Lourdes Garcia-Ortega & Jorge Andrade & Michael Potente & Rui Bened, 2021. "Arterialization requires the timely suppression of cell growth," Nature, Nature, vol. 589(7842), pages 437-441, January.
    2. Kenji Kamimoto & Blerta Stringa & Christy M. Hoffmann & Kunal Jindal & Lilianna Solnica-Krezel & Samantha A. Morris, 2023. "Dissecting cell identity via network inference and in silico gene perturbation," Nature, Nature, vol. 614(7949), pages 742-751, February.
    3. Nicholas W. Chavkin & Gael Genet & Mathilde Poulet & Erin D. Jeffery & Corina Marziano & Nafiisha Genet & Hema Vasavada & Elizabeth A. Nelson & Bipul R. Acharya & Anupreet Kour & Jordon Aragon & Steph, 2022. "Endothelial cell cycle state determines propensity for arterial-venous fate," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Suoqin Jin & Christian F. Guerrero-Juarez & Lihua Zhang & Ivan Chang & Raul Ramos & Chen-Hsiang Kuan & Peggy Myung & Maksim V. Plikus & Qing Nie, 2021. "Inference and analysis of cell-cell communication using CellChat," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    5. Tianying Su & Geoff Stanley & Rahul Sinha & Gaetano D’Amato & Soumya Das & Siyeon Rhee & Andrew H. Chang & Aruna Poduri & Brian Raftrey & Thanh Theresa Dinh & Walter A. Roper & Guang Li & Kelsey E. Qu, 2018. "Single-cell analysis of early progenitor cells that build coronary arteries," Nature, Nature, vol. 559(7714), pages 356-362, July.
    6. Tuomas Tammela & Georgia Zarkada & Elisabet Wallgard & Aino Murtomäki & Steven Suchting & Maria Wirzenius & Marika Waltari & Mats Hellström & Tibor Schomber & Reetta Peltonen & Catarina Freitas & Anto, 2008. "Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation," Nature, Nature, vol. 454(7204), pages 656-660, July.
    7. Kunhua Song & Young-Jae Nam & Xiang Luo & Xiaoxia Qi & Wei Tan & Guo N. Huang & Asha Acharya & Christopher L. Smith & Michelle D. Tallquist & Eric G. Neilson & Joseph A. Hill & Rhonda Bassel-Duby & Er, 2012. "Heart repair by reprogramming non-myocytes with cardiac transcription factors," Nature, Nature, vol. 485(7400), pages 599-604, May.
    8. Li Qian & Yu Huang & C. Ian Spencer & Amy Foley & Vasanth Vedantham & Lei Liu & Simon J. Conway & Ji-dong Fu & Deepak Srivastava, 2012. "In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes," Nature, Nature, vol. 485(7400), pages 593-598, 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. 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.
    2. Emre Bektik & Adrienne Dennis & Prateek Prasanna & Anant Madabhushi & Ji-Dong Fu, 2017. "Single cell qPCR reveals that additional HAND2 and microRNA-1 facilitate the early reprogramming progress of seven-factor-induced human myocytes," PLOS ONE, Public Library of Science, vol. 12(8), pages 1-16, August.
    3. Nicholas W. Chavkin & Gael Genet & Mathilde Poulet & Erin D. Jeffery & Corina Marziano & Nafiisha Genet & Hema Vasavada & Elizabeth A. Nelson & Bipul R. Acharya & Anupreet Kour & Jordon Aragon & Steph, 2022. "Endothelial cell cycle state determines propensity for arterial-venous fate," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Omar M. Hedaya & Kadiam C. Venkata Subbaiah & Feng Jiang & Li Huitong Xie & Jiangbin Wu & Eng-Soon Khor & Mingyi Zhu & David H. Mathews & Chris Proschel & Peng Yao, 2023. "Secondary structures that regulate mRNA translation provide insights for ASO-mediated modulation of cardiac hypertrophy," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Ki Oh & Yun Jae Yoo & Luke A. Torre-Healy & Manisha Rao & Danielle Fassler & Pei Wang & Michael Caponegro & Mei Gao & Joseph Kim & Aaron Sasson & Georgios Georgakis & Scott Powers & Richard A. Moffitt, 2023. "Coordinated single-cell tumor microenvironment dynamics reinforce pancreatic cancer subtype," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    6. Laetitia Préau & Anna Lischke & Melanie Merkel & Neslihan Oegel & Maria Weissenbruch & Andria Michael & Hongryeol Park & Dietmar Gradl & Christian Kupatt & Ferdinand Noble, 2024. "Parenchymal cues define Vegfa-driven venous angiogenesis by activating a sprouting competent venous endothelial subtype," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    7. Xiaoying Wang & Maoteng Duan & Jingxian Li & Anjun Ma & Gang Xin & Dong Xu & Zihai Li & Bingqiang Liu & Qin Ma, 2024. "MarsGT: Multi-omics analysis for rare population inference using single-cell graph transformer," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    8. 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.
    9. Qingnan Liang & Yuefan Huang & Shan He & Ken Chen, 2023. "Pathway centric analysis for single-cell RNA-seq and spatial transcriptomics data with GSDensity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    10. Maria A. Missinato & Sean Murphy & Michaela Lynott & Michael S. Yu & Anaïs Kervadec & Yu-Ling Chang & Suraj Kannan & Mafalda Loreti & Christopher Lee & Prashila Amatya & Hiroshi Tanaka & Chun-Teng Hua, 2023. "Conserved transcription factors promote cell fate stability and restrict reprogramming potential in differentiated cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    11. Faith H. Brennan & Yang Li & Cankun Wang & Anjun Ma & Qi Guo & Yi Li & Nicole Pukos & Warren A. Campbell & Kristina G. Witcher & Zhen Guan & Kristina A. Kigerl & Jodie C. E. Hall & Jonathan P. Godbout, 2022. "Microglia coordinate cellular interactions during spinal cord repair in mice," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    12. Sandra Curras-Alonso & Juliette Soulier & Thomas Defard & Christian Weber & Sophie Heinrich & Hugo Laporte & Sophie Leboucher & Sonia Lameiras & Marie Dutreix & Vincent Favaudon & Florian Massip & Tho, 2023. "An interactive murine single-cell atlas of the lung responses to radiation injury," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    13. Moujtaba Y. Kasmani & Paytsar Topchyan & Ashley K. Brown & Ryan J. Brown & Xiaopeng Wu & Yao Chen & Achia Khatun & Donia Alson & Yue Wu & Robert Burns & Chien-Wei Lin & Matthew R. Kudek & Jie Sun & We, 2023. "A spatial sequencing atlas of age-induced changes in the lung during influenza infection," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    14. Wei Yang & Li-Bo Liu & Feng-Liang Liu & Yan-Hua Wu & Zi-Da Zhen & Dong-Ying Fan & Zi-Yang Sheng & Zheng-Ran Song & Jia-Tong Chang & Yong-Tang Zheng & Jing An & Pei-Gang Wang, 2023. "Single-cell RNA sequencing reveals the fragility of male spermatogenic cells to Zika virus-induced complement activation," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    15. Xiaojian Lu & Yanwei Luo & Xichen Nie & Bailing Zhang & Xiaoyan Wang & Ran Li & Guangmin Liu & Qianyin Zhou & Zhizhong Liu & Liqing Fan & James M. Hotaling & Zhe Zhang & Hao Bo & Jingtao Guo, 2023. "Single-cell multi-omics analysis of human testicular germ cell tumor reveals its molecular features and microenvironment," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    16. Anjun Ma & Xiaoying Wang & Jingxian Li & Cankun Wang & Tong Xiao & Yuntao Liu & Hao Cheng & Juexin Wang & Yang Li & Yuzhou Chang & Jinpu Li & Duolin Wang & Yuexu Jiang & Li Su & Gang Xin & Shaopeng Gu, 2023. "Single-cell biological network inference using a heterogeneous graph transformer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    17. 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.
    18. Junjun Jing & Jifan Feng & Yuan Yuan & Tingwei Guo & Jie Lei & Fei Pei & Thach-Vu Ho & Yang Chai, 2022. "Spatiotemporal single-cell regulatory atlas reveals neural crest lineage diversification and cellular function during tooth morphogenesis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    19. 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.
    20. Nunya Chotiwan & Ebba Rosendal & Stefanie M. A. Willekens & Erin Schexnaydre & Emma Nilsson & Richard Lindqvist & Max Hahn & Ionut Sebastian Mihai & Federico Morini & Jianguo Zhang & Gregory D. Ebel &, 2023. "Type I interferon shapes brain distribution and tropism of tick-borne flavivirus," Nature Communications, Nature, vol. 14(1), pages 1-18, 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:15:y:2024:i:1:d:10.1038_s41467-024-48354-6. 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.