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Accepted Manuscript
RESEARCH ARTICLE
A novel role for Lyl1 in primitive erythropoiesis
Sung K. Chiu, Jesslyn Saw, Yizhou Huang, Stefan E. Sonderegger, Nicholas C. Wong, David R. Powell, Dominic Beck, John E. Pimanda, Cedric S. Tremblay, David J. Curtis
Development 2018 : dev.162990 doi: 10.1242/dev.162990 Published 5 September 2018
Sung K. Chiu
Australian Centre for Blood Diseases, Monash University, Melbourne, Australia
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Jesslyn Saw
Australian Centre for Blood Diseases, Monash University, Melbourne, Australia
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Yizhou Huang
Lowy Cancer Research Centre and the Prince of Wales Clinical School, University of New South Wales, Sydney, AustraliaCentre for Health Technologies, School of Biomedical Engineering and the School of Software, University of Technology, Sydney, Australia
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Stefan E. Sonderegger
Australian Centre for Blood Diseases, Monash University, Melbourne, Australia
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Nicholas C. Wong
Central Clinical School, Monash University, Melbourne, AustraliaBioinformatics Platform, Monash University, Melbourne, Australia
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David R. Powell
Bioinformatics Platform, Monash University, Melbourne, Australia
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Dominic Beck
Lowy Cancer Research Centre and the Prince of Wales Clinical School, University of New South Wales, Sydney, AustraliaCentre for Health Technologies, School of Biomedical Engineering and the School of Software, University of Technology, Sydney, Australia
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John E. Pimanda
Lowy Cancer Research Centre and the Prince of Wales Clinical School, University of New South Wales, Sydney, AustraliaDepartment of Haematology, Prince of Wales Hospital, Sydney, AustraliaDepartment of Pathology, School of Medical Sciences, University of New South Wales, Sydney, Australia
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Cedric S. Tremblay
Australian Centre for Blood Diseases, Monash University, Melbourne, Australia
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David J. Curtis
Australian Centre for Blood Diseases, Monash University, Melbourne, AustraliaDepartment of Clinical Haematology, The Alfred Hospital, Melbourne, Australia
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  • For correspondence: david.curtis@monash.edu
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Abstract

Stem Cell Leukemia (Scl or Tal1) and Lymphoblastic Leukemia 1 (Lyl1) are highly related members of the basic helix-loop-helix (bHLH) family of transcription factors that are co- expressed in the erythroid lineage. Previous studies suggest that Scl is essential for primitive erythropoiesis. However, analysis of single-cell RNA-sequencing data of early embryos showed that primitive erythroid cells express both Scl and Lyl1. Therefore, to determine whether Lyl1 can function in primitive erythropoiesis, we crossed conditional Scl knockout mice with mice expressing a Cre recombinase under the control of the Epo receptor, active in erythroid progenitors. Embryos with 20% expression of Scl from E9.5 survived to adulthood. However, mice with reduced expression of Scl and absence of Lyl1 (double knockout; DKO) died at E10.5 due to progressive loss of erythropoiesis. Gene expression profiling of DKO yolk sacs revealed loss of Gata1 and many of the known target genes of the SCL-GATA1 complex. ChIP-seq analyses showed that LYL1 exclusively bound a small subset of SCL targets including GATA1. Together, these data show for the first time that Lyl1 can maintain primitive erythropoiesis.

  • Received January 4, 2018.
  • Accepted August 28, 2018.
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Keywords

  • Primitive erythropoiesis
  • Transcription factors
  • Scl (Tal1)
  • Lyl1

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Accepted Manuscript
RESEARCH ARTICLE
A novel role for Lyl1 in primitive erythropoiesis
Sung K. Chiu, Jesslyn Saw, Yizhou Huang, Stefan E. Sonderegger, Nicholas C. Wong, David R. Powell, Dominic Beck, John E. Pimanda, Cedric S. Tremblay, David J. Curtis
Development 2018 : dev.162990 doi: 10.1242/dev.162990 Published 5 September 2018
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Accepted Manuscript
RESEARCH ARTICLE
A novel role for Lyl1 in primitive erythropoiesis
Sung K. Chiu, Jesslyn Saw, Yizhou Huang, Stefan E. Sonderegger, Nicholas C. Wong, David R. Powell, Dominic Beck, John E. Pimanda, Cedric S. Tremblay, David J. Curtis
Development 2018 : dev.162990 doi: 10.1242/dev.162990 Published 5 September 2018

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