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Time-integrated BMP signaling determines fate in a stem cell model for early human development

Author

Listed:
  • Seth Teague

    (University of Michigan)

  • Gillian Primavera

    (University of Michigan)

  • Bohan Chen

    (University of Michigan Medical School)

  • Zong-Yuan Liu

    (University of Michigan Medical School)

  • LiAng Yao

    (University of Michigan Medical School)

  • Emily Freeburne

    (University of Michigan Medical School)

  • Hina Khan

    (University of Michigan Medical School)

  • Kyoung Jo

    (University of Michigan Medical School)

  • Craig Johnson

    (University of Michigan Medical School)

  • Idse Heemskerk

    (University of Michigan
    University of Michigan Medical School
    University of Michigan Medical School
    University of Michigan Medical School)

Abstract

How paracrine signals are interpreted to yield multiple cell fate decisions in a dynamic context during human development in vivo and in vitro remains poorly understood. Here we report an automated tracking method to follow signaling histories linked to cell fate in large numbers of human pluripotent stem cells (hPSCs). Using an unbiased statistical approach, we discover that measured BMP signaling history correlates strongly with fate in individual cells. We find that BMP response in hPSCs varies more strongly in the duration of signaling than the level. However, both the level and duration of signaling activity control cell fate choices only by changing the time integral. Therefore, signaling duration and level are interchangeable in this context. In a stem cell model for patterning of the human embryo, we show that signaling histories predict the fate pattern and that the integral model correctly predicts changes in cell fate domains when signaling is perturbed. Our data suggest that mechanistically, BMP signaling is integrated by SOX2.

Suggested Citation

  • Seth Teague & Gillian Primavera & Bohan Chen & Zong-Yuan Liu & LiAng Yao & Emily Freeburne & Hina Khan & Kyoung Jo & Craig Johnson & Idse Heemskerk, 2024. "Time-integrated BMP signaling determines fate in a stem cell model for early human development," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45719-9
    DOI: 10.1038/s41467-024-45719-9
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    References listed on IDEAS

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