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Asynchronous lineage priming determines commitment to T cell and B cell lineages in fetal liver

Nature Immunology volume 18, pages 11391149 (2017) | Download Citation

Abstract

The molecular events that initiate lymphoid-lineage specification remain unidentified because the stages of differentiation during which lineage commitment occurs are difficult to characterize. We isolated fetal liver progenitor cells undergoing restriction of their differentiation potential toward the T cell–innate lymphoid cell lineage or the B cell lineage. Transcripts that defined the molecular signatures of these two subsets were sequentially upregulated in lympho-myeloid precursor cells and in common lymphoid progenitor cells, respectively, and this preceded lineage restriction; this indicates that T cell–versus–B cell commitment is not a binary fate 'decision'. The T cell–bias and B cell–bias transcriptional programs were frequently co-expressed in common lymphoid progenitor cells and were segregated in subsets biased toward T cell differentiation or B cell differentiation, after interleukin 7 (IL-7) signaling that controlled the number of progenitor cells engaging in T cell differentiation versus B cell differentiation.

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Acknowledgements

We thank A. Bandeira and D. Guy-Grand for critical reading; S. Novault and S. Schmutz for support; H.-R. Rodewald (German Cancer Center DKFZ) for the IL-7Rα-Cre mouse line; and P. Chambon (IGBMC Strasbourg) for the TSLP-KO mice. This work benefited from data assembled by the ImmGen Consortium. Supported by the Pasteur Institute, Institut National de la Santé et de la Recherche Médicale (INSERM), the Ministère de la Recherche (C.B., C.R. and S.C.), Association pour la Recherche sur le Cancer (S.C. and R.G.), La Ligue Contre Le Cancer (C.B. and C.R.), Université Paris Diderot (C.B., R.G. and S.C.), Université Pierre et Marie Curie (C.R.), the Agence Nationale de la Recherche (project Myeloten (R.G.); program REVIVE (Investment for the Future) (A.C.); and project Twothyme (A.C.) and the Pasteur-Weizmann Foundation (A.C.).

Author information

Author notes

    • Claire Berthault
    •  & Cyrille Ramond

    Present address: Research Center Growth and Signaling, INSERM U 1016, Institut Cochin, Paris, France (C.B. and C.R.).

Affiliations

  1. Unit for Lymphopoiesis, Pasteur Institute, Paris, France. Immunology department.

    • Claire Berthault
    • , Cyrille Ramond
    • , Odile Burlen-Defranoux
    • , Sylvestre Chea
    • , Rachel Golub
    • , Pablo Pereira
    • , Paulo Vieira
    •  & Ana Cumano
  2. INSERM U1223, Paris, France.

    • Claire Berthault
    • , Cyrille Ramond
    • , Odile Burlen-Defranoux
    • , Sylvestre Chea
    • , Rachel Golub
    • , Pablo Pereira
    • , Paulo Vieira
    •  & Ana Cumano
  3. Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, Paris, France.

    • Claire Berthault
    • , Odile Burlen-Defranoux
    • , Sylvestre Chea
    • , Rachel Golub
    • , Pablo Pereira
    • , Paulo Vieira
    •  & Ana Cumano
  4. Université Pierre et Marie Curie, Paris, France.

    • Cyrille Ramond
  5. Département Génomes et Génétique, Plate-forme Transcriptome et Epigénome, Institut Pasteur, Paris, France.

    • Guillaume Soubigou

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Contributions

C.B. designed and performed most experiments, analyzed data and wrote the manuscript; C.R., O.B.-D. and S.C. performed experiments; G.S. performed the microarray; R.G. provided mouse lines and designed experiments; C.R., P.P. and P.V. contributed to the discussions and writing; and A.C. directed the research, designed experiments, analyzed data and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ana Cumano.

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https://doi.org/10.1038/ni.3820