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Stochastic priming and spatial cues orchestrate heterogeneous clonal contribution to mouse pancreas organogenesis

Author

Listed:
  • Hjalte List Larsen

    (DanStem, University of Copenhagen)

  • Laura Martín-Coll

    (DanStem, University of Copenhagen)

  • Alexander Valentin Nielsen

    (Niels Bohr Institute, University of Copenhagen)

  • Christopher V. E. Wright

    (Vanderbilt University)

  • Ala Trusina

    (Niels Bohr Institute, University of Copenhagen)

  • Yung Hae Kim

    (DanStem, University of Copenhagen)

  • Anne Grapin-Botton

    (DanStem, University of Copenhagen)

Abstract

Spatiotemporal balancing of cellular proliferation and differentiation is crucial for postnatal tissue homoeostasis and organogenesis. During embryonic development, pancreatic progenitors simultaneously proliferate and differentiate into the endocrine, ductal and acinar lineages. Using in vivo clonal analysis in the founder population of the pancreas here we reveal highly heterogeneous contribution of single progenitors to organ formation. While some progenitors are bona fide multipotent and contribute progeny to all major pancreatic cell lineages, we also identify numerous unipotent endocrine and ducto-endocrine bipotent clones. Single-cell transcriptional profiling at E9.5 reveals that endocrine-committed cells are molecularly distinct, whereas multipotent and bipotent progenitors do not exhibit different expression profiles. Clone size and composition support a probabilistic model of cell fate allocation and in silico simulations predict a transient wave of acinar differentiation around E11.5, while endocrine differentiation is proportionally decreased. Increased proliferative capacity of outer progenitors is further proposed to impact clonal expansion.

Suggested Citation

  • Hjalte List Larsen & Laura Martín-Coll & Alexander Valentin Nielsen & Christopher V. E. Wright & Ala Trusina & Yung Hae Kim & Anne Grapin-Botton, 2017. "Stochastic priming and spatial cues orchestrate heterogeneous clonal contribution to mouse pancreas organogenesis," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00258-4
    DOI: 10.1038/s41467-017-00258-4
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    Cited by:

    1. Xiaochan Xu & Philip Allan Seymour & Kim Sneppen & Ala Trusina & Anuska la Rosa Egeskov-Madsen & Mette Christine Jørgensen & Mogens Høgh Jensen & Palle Serup, 2023. "Jag1-Notch cis-interaction determines cell fate segregation in pancreatic development," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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