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

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 inhibite...

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Main Authors: Duarte, S, Woll, P, Buza-Vidas, N, Chin, D, Boukarabila, H, Luís, T, Stenson, L, Bouriez-Jones, T, Ferry, H, Mead, A, Atkinson, D, Jin, S, Clark, S, Wu, B, Repapi, E, Gray, N, Taylor, S, Mutvei, A, Tsoi, Y, Nerlov, C, Lendahl, U, Jacobsen, S
Format: Journal article
Language:English
Published: American Society of Hematology 2018
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author Duarte, S
Woll, P
Buza-Vidas, N
Chin, D
Boukarabila, H
Luís, T
Stenson, L
Bouriez-Jones, T
Ferry, H
Mead, A
Atkinson, D
Jin, S
Clark, S
Wu, B
Repapi, E
Gray, N
Taylor, S
Mutvei, A
Tsoi, Y
Nerlov, C
Lendahl, U
Jacobsen, S
author_facet Duarte, S
Woll, P
Buza-Vidas, N
Chin, D
Boukarabila, H
Luís, T
Stenson, L
Bouriez-Jones, T
Ferry, H
Mead, A
Atkinson, D
Jin, S
Clark, S
Wu, B
Repapi, E
Gray, N
Taylor, S
Mutvei, A
Tsoi, Y
Nerlov, C
Lendahl, U
Jacobsen, S
author_sort Duarte, S
collection OXFORD
description 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.
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spelling oxford-uuid:6fa5cf63-6f03-40b0-b629-11803f1ee8a42022-03-26T19:31:57ZCanonical Notch signaling is dispensible for adult steady-state and stress myelo-erythropoiesisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6fa5cf63-6f03-40b0-b629-11803f1ee8a4EnglishSymplectic Elements at OxfordAmerican Society of Hematology2018Duarte, SWoll, PBuza-Vidas, NChin, DBoukarabila, HLuís, TStenson, LBouriez-Jones, TFerry, HMead, AAtkinson, DJin, SClark, SWu, BRepapi, EGray, NTaylor, SMutvei, ATsoi, YNerlov, CLendahl, UJacobsen, SWhile 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.
spellingShingle Duarte, S
Woll, P
Buza-Vidas, N
Chin, D
Boukarabila, H
Luís, T
Stenson, L
Bouriez-Jones, T
Ferry, H
Mead, A
Atkinson, D
Jin, S
Clark, S
Wu, B
Repapi, E
Gray, N
Taylor, S
Mutvei, A
Tsoi, Y
Nerlov, C
Lendahl, U
Jacobsen, S
Canonical Notch signaling is dispensible for adult steady-state and stress myelo-erythropoiesis
title Canonical Notch signaling is dispensible for adult steady-state and stress myelo-erythropoiesis
title_full Canonical Notch signaling is dispensible for adult steady-state and stress myelo-erythropoiesis
title_fullStr Canonical Notch signaling is dispensible for adult steady-state and stress myelo-erythropoiesis
title_full_unstemmed Canonical Notch signaling is dispensible for adult steady-state and stress myelo-erythropoiesis
title_short Canonical Notch signaling is dispensible for adult steady-state and stress myelo-erythropoiesis
title_sort canonical notch signaling is dispensible for adult steady state and stress myelo erythropoiesis
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