Cutting edge: Lymphomyeloid-primed progenitor cell fates are controlled by the transcription factor TAL1

Renée F. De Pooter; Sheila Dias; Munmun Chowdhury; Elisabeth T. Bartom; Michael K. Okoreeh; Mikael Sigvardsson; Barbara L. Kee

doi:10.4049/jimmunol.1801220

Cutting edge: Lymphomyeloid-primed progenitor cell fates are controlled by the transcription factor TAL1

Renée F. De Pooter, Sheila Dias, Munmun Chowdhury, Elisabeth T. Bartom, Michael K. Okoreeh, Mikael Sigvardsson, Barbara L. Kee^*

^*Corresponding author for this work

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Lymphoid specification is the process by which hematopoietic stem cells (HSCs) and their progeny become restricted to differentiation through the lymphoid lineages. The basic helix-loop-helix transcription factors E2A and Lyl1 form a complex that promotes lymphoid specification. In this study, we demonstrate that Tal1, a Lyl1-related basic helix-loop-helix transcription factor that promotes T acute lymphoblastic leukemia and is required for HSC specification, erythropoiesis, and megakaryopoiesis, is a negative regulator of murine lymphoid specification. We demonstrate that Tal1 limits the expression of multiple E2A target genes in HSCs and controls the balance of myeloid versus T lymphocyte differentiation potential in lymphomyeloid-primed progenitors. Our data provide insight into the mechanisms controlling lymphocyte specification and may reveal a basis for the unique functions of Tal1 and Lyl1 in T acute lymphoblastic leukemia.

Original language	English (US)
Pages (from-to)	2837-2842
Number of pages	6
Journal	Journal of Immunology
Volume	202
Issue number	10
DOIs	https://doi.org/10.4049/jimmunol.1801220
State	Published - May 15 2019

Funding

This work was supported by funding provided by the Leukemia and Lymphoma Society (to R.F.d.P.) and National Institutes of Health R01 AI1078267 and R01 AI106352 (to B.L.K.) and T32HD007009 (to M.K.O.).

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.4049/jimmunol.1801220

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title = "Cutting edge: Lymphomyeloid-primed progenitor cell fates are controlled by the transcription factor TAL1",

abstract = "Lymphoid specification is the process by which hematopoietic stem cells (HSCs) and their progeny become restricted to differentiation through the lymphoid lineages. The basic helix-loop-helix transcription factors E2A and Lyl1 form a complex that promotes lymphoid specification. In this study, we demonstrate that Tal1, a Lyl1-related basic helix-loop-helix transcription factor that promotes T acute lymphoblastic leukemia and is required for HSC specification, erythropoiesis, and megakaryopoiesis, is a negative regulator of murine lymphoid specification. We demonstrate that Tal1 limits the expression of multiple E2A target genes in HSCs and controls the balance of myeloid versus T lymphocyte differentiation potential in lymphomyeloid-primed progenitors. Our data provide insight into the mechanisms controlling lymphocyte specification and may reveal a basis for the unique functions of Tal1 and Lyl1 in T acute lymphoblastic leukemia.",

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AU - De Pooter, Renée F.

AU - Dias, Sheila

AU - Chowdhury, Munmun

AU - Bartom, Elisabeth T.

AU - Okoreeh, Michael K.

AU - Sigvardsson, Mikael

AU - Kee, Barbara L.

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N2 - Lymphoid specification is the process by which hematopoietic stem cells (HSCs) and their progeny become restricted to differentiation through the lymphoid lineages. The basic helix-loop-helix transcription factors E2A and Lyl1 form a complex that promotes lymphoid specification. In this study, we demonstrate that Tal1, a Lyl1-related basic helix-loop-helix transcription factor that promotes T acute lymphoblastic leukemia and is required for HSC specification, erythropoiesis, and megakaryopoiesis, is a negative regulator of murine lymphoid specification. We demonstrate that Tal1 limits the expression of multiple E2A target genes in HSCs and controls the balance of myeloid versus T lymphocyte differentiation potential in lymphomyeloid-primed progenitors. Our data provide insight into the mechanisms controlling lymphocyte specification and may reveal a basis for the unique functions of Tal1 and Lyl1 in T acute lymphoblastic leukemia.

AB - Lymphoid specification is the process by which hematopoietic stem cells (HSCs) and their progeny become restricted to differentiation through the lymphoid lineages. The basic helix-loop-helix transcription factors E2A and Lyl1 form a complex that promotes lymphoid specification. In this study, we demonstrate that Tal1, a Lyl1-related basic helix-loop-helix transcription factor that promotes T acute lymphoblastic leukemia and is required for HSC specification, erythropoiesis, and megakaryopoiesis, is a negative regulator of murine lymphoid specification. We demonstrate that Tal1 limits the expression of multiple E2A target genes in HSCs and controls the balance of myeloid versus T lymphocyte differentiation potential in lymphomyeloid-primed progenitors. Our data provide insight into the mechanisms controlling lymphocyte specification and may reveal a basis for the unique functions of Tal1 and Lyl1 in T acute lymphoblastic leukemia.

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Cutting edge: Lymphomyeloid-primed progenitor cell fates are controlled by the transcription factor TAL1

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