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Canonical Notch signaling is dispensible for adult steady-state and stress myelo-erythropoiesis

Sara Duarte, Petter S. Woll, Natalija Buza-Vidas, Desmond Wai Loon Chin, Hanane Boukarabila, Tiago C. Luís, Laura Stenson, Tiphaine Bouriez-Jones, Helen Ferry, Adam J. Mead, Deborah Atkinson, Shaobo Jin, Sally-Ann Clark, Bishan Wu, Emmanouela Repapi, Nicki Gray, Stephen Taylor, Anders P. Mutvei, Yat Long Tsoi, Claus Nerlov, Urban Lendahl and Sten Eirik W. Jacobsen

Key points

  • Canonical Notch signaling is dispensable for steady-state and post-transplantation myelopoiesis as well as stress erythropoiesis.

  • Key lineage regulators and Notch target genes are expressed independently of canonical Notch-signaling in myelo-erythropoiesis.

Abstract

While an essential role for canonical Notch signaling in generation of hematopoietic stem cells in the embryo and in thymic T cell development is well established, its role in adult bone marrow (BM) myelopoiesis remains unclear. Some studies, analyzing myeloid progenitors in adult mice with inhibited Notch signaling, implicated distinct roles of canonical Notch signaling in regulation of progenitors for the megakaryocyte, erythroid and granulocyte-macrophage cell lineages. However, these studies might also have targeted other pathways. Therefore, we specifically deleted, in adult BM, the transcription factor recombination signal-binding protein J kappa (Rbpj), which canonical signaling through all Notch receptors converges. Notably, detailed progenitor staging established that canonical Notch signaling is fully dispensable for all investigated stages of megakaryocyte, erythroid and myeloid progenitors, in steady state unperturbed hematopoiesis, following competitive BM transplantation and in stress-induced erythropoiesis. Moreover, expression of key regulators of these hematopoietic lineages and Notch target genes were unaffected by Rbpj-deficiency in BM progenitor cells.

  • Submitted June 2, 2017.
  • Accepted January 10, 2018.