A novel role for Lyl1 in primitive erythropoiesis

Sung Kai Chiu, Jesslyn Mei Yoong Saw, Yizhou Huang, Stefan Eugen Sonderegger, Nicholas Chau Lun Wong, David Richard Powell, Dominic Beck, John Pimanda, Cedric Tremblay, David John Curtis

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Stem cell leukemia (Scl or Tal1) and lymphoblastic leukemia 1 (Lyl1) encode highly related members of the basic helix-loop-helix family of transcription factors that are co-expressed in the erythroid lineage. Previous studies have suggested that Scl is essential for primitive erythropoiesis. However, analysis of single-cell RNA-seq 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 because of 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 in a human erythroleukemia cell line 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.

Original languageEnglish
Article numberdev162990
Number of pages9
JournalDevelopment
Volume145
Issue number19
DOIs
Publication statusPublished - 11 Oct 2018

Keywords

  • LYL1
  • Mouse
  • Primitive erythropoiesis
  • SCL (TAL1)
  • Transcription factors

Cite this

Chiu, Sung Kai ; Saw, Jesslyn Mei Yoong ; Huang, Yizhou ; Sonderegger, Stefan Eugen ; Wong, Nicholas Chau Lun ; Powell, David Richard ; Beck, Dominic ; Pimanda, John ; Tremblay, Cedric ; Curtis, David John. / A novel role for Lyl1 in primitive erythropoiesis. In: Development. 2018 ; Vol. 145, No. 19.
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abstract = "Stem cell leukemia (Scl or Tal1) and lymphoblastic leukemia 1 (Lyl1) encode highly related members of the basic helix-loop-helix family of transcription factors that are co-expressed in the erythroid lineage. Previous studies have suggested that Scl is essential for primitive erythropoiesis. However, analysis of single-cell RNA-seq 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 because of 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 in a human erythroleukemia cell line 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.",
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Chiu, SK, Saw, JMY, Huang, Y, Sonderegger, SE, Wong, NCL, Powell, DR, Beck, D, Pimanda, J, Tremblay, C & Curtis, DJ 2018, 'A novel role for Lyl1 in primitive erythropoiesis' Development, vol. 145, no. 19, dev162990. https://doi.org/10.1242/dev.162990

A novel role for Lyl1 in primitive erythropoiesis. / Chiu, Sung Kai; Saw, Jesslyn Mei Yoong; Huang, Yizhou; Sonderegger, Stefan Eugen; Wong, Nicholas Chau Lun; Powell, David Richard; Beck, Dominic; Pimanda, John; Tremblay, Cedric; Curtis, David John.

In: Development, Vol. 145, No. 19, dev162990, 11.10.2018.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Chiu, Sung Kai

AU - Saw, Jesslyn Mei Yoong

AU - Huang, Yizhou

AU - Sonderegger, Stefan Eugen

AU - Wong, Nicholas Chau Lun

AU - Powell, David Richard

AU - Beck, Dominic

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AU - Curtis, David John

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AB - Stem cell leukemia (Scl or Tal1) and lymphoblastic leukemia 1 (Lyl1) encode highly related members of the basic helix-loop-helix family of transcription factors that are co-expressed in the erythroid lineage. Previous studies have suggested that Scl is essential for primitive erythropoiesis. However, analysis of single-cell RNA-seq 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 because of 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 in a human erythroleukemia cell line 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.

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DO - 10.1242/dev.162990

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JO - Development

JF - Development

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Chiu SK, Saw JMY, Huang Y, Sonderegger SE, Wong NCL, Powell DR et al. A novel role for Lyl1 in primitive erythropoiesis. Development. 2018 Oct 11;145(19). dev162990. https://doi.org/10.1242/dev.162990