1. Cell Biology
  2. Developmental Biology

Transcriptional drifts associated with environmental changes in endothelial cells

  1. Yalda Afshar  Is a corresponding author
  2. Feyiang Ma
  3. Austin Quach
  4. Anhyo Jeong
  5. Hannah L Sunshine
  6. Vanessa Freitas
  7. Yasaman Jami-Alahmadi
  8. Raphael Helaers
  9. Xinmin Li
  10. Matteo Pellegrini
  11. James A Wohlschlegel
  12. Casey E Romanoski
  13. Miikka Vikkula
  14. Luisa Iruela-Arispe
  1. University of California, Los Angeles, United States
  2. Northwestern University, United States
  3. University of São Paulo, Brazil
  4. University of Louvain, Belgium
  5. University of Arizona, United States
https://doi.org/10.7554/eLife.81370
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Cite this article
  1. Yalda Afshar
  2. Feyiang Ma
  3. Austin Quach
  4. Anhyo Jeong
  5. Hannah L Sunshine
  6. Vanessa Freitas
  7. Yasaman Jami-Alahmadi
  8. Raphael Helaers
  9. Xinmin Li
  10. Matteo Pellegrini
  11. James A Wohlschlegel
  12. Casey E Romanoski
  13. Miikka Vikkula
  14. Luisa Iruela-Arispe
(2023)
Transcriptional drifts associated with environmental changes in endothelial cells
eLife 12:e81370.
https://doi.org/10.7554/eLife.81370
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Abstract

Environmental cues, such as physical forces and heterotypic cell interactions play a critical role in cell function, yet their collective contributions to transcriptional changes are unclear. Focusing on human endothelial cells, we performed broad individual sample analysis to identify transcriptional drifts associated with environmental changes that were independent of genetic background. Global gene expression profiling by RNAseq and protein expression by LC-MS directed proteomics distinguished endothelial cells in vivo from genetically matched culture (in vitro) samples. Over 43% of the transcriptome was significantly changed by the in vitro environment. Subjecting cultured cells to long-term shear stress significantly rescued the expression of approximately 17% of genes. Inclusion of heterotypic interactions by co-culture of endothelial cells with smooth muscle cells normalized approximately 9% of the original in vivo signature. We also identified novel flow dependent genes, as well as genes that necessitate heterotypic cell interactions to mimic the in vivo transcriptome. Our findings highlight specific genes and pathways that rely on contextual information for adequate expression from those that are agnostic of such environmental cues.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file, Source Data files have been provided

The following previously published data sets were used

Article and author information

Author details

  1. Yalda Afshar

    Department of Obstetrics and Gynecology, University of California, Los Angeles, Los Angeles, United States
    For correspondence
    YAfshar@mednet.ucla.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3807-7022

  2. Feyiang Ma

    Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Austin Quach

    Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Anhyo Jeong

    Department of Obstetrics and Gynecology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Hannah L Sunshine

    Department of Cell and Developmental Biology, Northwestern University, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Vanessa Freitas

    Departament of Cell and Developmental Biology, University of São Paulo, São Paulo, Brazil
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9613-8626

  7. Yasaman Jami-Alahmadi

    Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8289-2222

  8. Raphael Helaers

    Human Molecular Genetics, University of Louvain, Brussels, Belgium
    Competing interests
    The authors declare that no competing interests exist.

  9. Xinmin Li

    Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. Matteo Pellegrini

    Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  11. James A Wohlschlegel

    Departament of Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  12. Casey E Romanoski

    Department of Cellular and Molecular Medicine, University of Arizona, Tucson, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0149-225X

  13. Miikka Vikkula

    Human Molecular Genetics, University of Louvain, Brussels, Belgium
    Competing interests
    The authors declare that no competing interests exist.

  14. Luisa Iruela-Arispe

    Department of Cell and Developmental Biology, Northwestern University, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3050-4168

Funding

National Institutes of Health (R35HL140014)

  • Luisa Iruela-Arispe

National Institutes of Health (R01HL147187)

  • Casey E Romanoski

Foundation for the National Institutes of Health (FAPESP 2016/19968-3)

  • Vanessa Freitas

National Institutes of Health (K12 HD000849)

  • Yalda Afshar

National Institutes of Health (T32HL069766)

  • Yalda Afshar

Fondation Leducq (21CVD03)

  • Miikka Vikkula
  • Luisa Iruela-Arispe

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Human umbilical cords were collected under Institutional Review Board (UCLA IRB#16-001694) at time of the delivery and processed 2-4 hours from time of birth. All samples were collected from patients who provided signed informed consent.

Reviewing Editor

  1. Ilse S Daehn, Icahn School of Medicine at Mount Sinai, United States

Version history

  1. Received: June 24, 2022
  2. Preprint posted: July 9, 2022 (view preprint)
  3. Accepted: March 26, 2023
  4. Accepted Manuscript published: March 27, 2023 (version 1)
  5. Accepted Manuscript updated: March 29, 2023 (version 2)
  6. Version of Record published: May 9, 2023 (version 3)

Copyright

© 2023, Afshar et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Yalda Afshar
  2. Feyiang Ma
  3. Austin Quach
  4. Anhyo Jeong
  5. Hannah L Sunshine
  6. Vanessa Freitas
  7. Yasaman Jami-Alahmadi
  8. Raphael Helaers
  9. Xinmin Li
  10. Matteo Pellegrini
  11. James A Wohlschlegel
  12. Casey E Romanoski
  13. Miikka Vikkula
  14. Luisa Iruela-Arispe
(2023)
Transcriptional drifts associated with environmental changes in endothelial cells
eLife 12:e81370.
https://doi.org/10.7554/eLife.81370

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