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 language | English |
|---|---|
| Article number | dev162990 |
| Number of pages | 9 |
| Journal | Development |
| Volume | 145 |
| Issue number | 19 |
| DOIs | |
| Publication status | Published - 11 Oct 2018 |
Keywords
- LYL1
- Mouse
- Primitive erythropoiesis
- SCL (TAL1)
- Transcription factors
Cite this
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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 journal › Article › Research › peer-review
TY - JOUR
T1 - A novel role for Lyl1 in primitive erythropoiesis
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
AU - Pimanda, John
AU - Tremblay, Cedric
AU - Curtis, David John
PY - 2018/10/11
Y1 - 2018/10/11
N2 - 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.
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.
KW - LYL1
KW - Mouse
KW - Primitive erythropoiesis
KW - SCL (TAL1)
KW - Transcription factors
UR - http://www.scopus.com/inward/record.url?scp=85054750724&partnerID=8YFLogxK
U2 - 10.1242/dev.162990
DO - 10.1242/dev.162990
M3 - Article
VL - 145
JO - Development
JF - Development
SN - 0950-1991
IS - 19
M1 - dev162990
ER -