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Transcriptional dynamics and epigenetic regulation of E and ID protein encoding genes during human T cell development.

ABSTRACT: T cells are generated from hematopoietic stem cells through a highly organized developmental process, in which stage-specific molecular events drive maturation towards αβ and γδ T cells. Although many of the mechanisms that control αβ- and γδ-lineage differentiation are shared between human and mouse, important differences have also been observed. Here, we studied the regulatory dynamics of the E and ID protein encoding genes during pediatric human T cell development by evaluating changes in chromatin accessibility, histone modifications and bulk and single cell gene expression. We profiled patterns of ID/E protein activity and identified up- and downstream regulators and targets, respectively. In addition, we compared transcription of E and ID protein encoding genes in human versus mouse to predict both shared and unique activities in these species, and in prenatal versus pediatric human T cell differentiation to identify regulatory changes during development. This analysis showed a putative involvement of TCF3/E2A in the development of γδ T cells. In contrast, in αβ T cell precursors a pivotal pre-TCR-driven population with high ID gene expression and low predicted E protein activity was identified. Finally, in prenatal but not postnatal thymocytes, high HEB/TCF12 levels were found to counteract high ID levels to sustain thymic development. In summary, we uncovered novel insights in the regulation of E and ID proteins on a cross-species and cross-developmental level.

SUBMITTER: Roels J

PROVIDER: S-EPMC9366357 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Transcriptional dynamics and epigenetic regulation of E and ID protein encoding genes during human T cell development.

Roels Juliette J Van Hulle Jolien J Lavaert Marieke M Kuchmiy Anna A Strubbe Steven S Putteman Tom T Vandekerckhove Bart B Leclercq Georges G Van Nieuwerburgh Filip F Boehme Lena L Taghon Tom T

Frontiers in immunology 20220728

T cells are generated from hematopoietic stem cells through a highly organized developmental process, in which stage-specific molecular events drive maturation towards αβ and γδ T cells. Although many of the mechanisms that control αβ- and γδ-lineage differentiation are shared between human and mouse, important differences have also been observed. Here, we studied the regulatory dynamics of the E and ID protein encoding genes during pediatric human T cell development by evaluating changes in chr ...[more]

PMID: 35967340

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Transcriptional dynamics and epigenetic regulation of E and ID protein encoding genes during human T cell development.

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Transcriptional dynamics and epigenetic regulation of E and ID protein encoding genes during human T cell development.

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