ThPOK is a critical multifaceted regulator of myeloid lineage development

Jayati Basu; Andre Olsson; Kyle Ferchen; Elizaveta K. Titerina; Kashish Chetal; Emmanuelle Nicolas; Philip Czyzewicz; Dmitry Levchenko; Lu Ge; Xiang Hua; H. Leighton Grimes; Nathan Salomonis; Dietmar J. Kappes

doi:10.1038/s41590-023-01549-3

ThPOK is a critical multifaceted regulator of myeloid lineage development

Jayati Basu
, Andre Olsson
, Kyle Ferchen
, Elizaveta K. Titerina
, Kashish Chetal
, Emmanuelle Nicolas
, Philip Czyzewicz
, Dmitry Levchenko
, Lu Ge
, Xiang Hua
, H. Leighton Grimes
, Nathan Salomonis
, Dietmar J. Kappes

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

3 Scopus citations

Abstract

The transcription factor ThPOK (encoded by Zbtb7b) is well known for its role as a master regulator of CD4 lineage commitment in the thymus. Here, we report an unexpected and critical role of ThPOK as a multifaceted regulator of myeloid lineage commitment, differentiation and maturation. Using reporter and knockout mouse models combined with single-cell RNA-sequencing, progenitor transfer and colony assays, we show that ThPOK controls monocyte-dendritic cell versus granulocyte lineage production during homeostatic differentiation, and serves as a brake for neutrophil maturation in granulocyte lineage-specified cells through transcriptional regulation of lineage-specific transcription factors and RNA via altered messenger RNA splicing to reprogram intron retention.

Original language	English
Pages (from-to)	1295-1307
Number of pages	13
Journal	Nature Immunology
Volume	24
Issue number	8
Early online date	Jul 20 2023
DOIs	https://doi.org/10.1038/s41590-023-01549-3
State	Published - Aug 2023

Keywords

Animals
CD4 Antigens
Cell Differentiation
Cell Lineage
DNA-Binding Proteins
Gene Expression Regulation
Mice
Mice, Knockout
RNA
Thymus Gland
Transcription Factors/genetics

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10.1038/s41590-023-01549-3

Cite this

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title = "ThPOK is a critical multifaceted regulator of myeloid lineage development",

abstract = "The transcription factor ThPOK (encoded by Zbtb7b) is well known for its role as a master regulator of CD4 lineage commitment in the thymus. Here, we report an unexpected and critical role of ThPOK as a multifaceted regulator of myeloid lineage commitment, differentiation and maturation. Using reporter and knockout mouse models combined with single-cell RNA-sequencing, progenitor transfer and colony assays, we show that ThPOK controls monocyte-dendritic cell versus granulocyte lineage production during homeostatic differentiation, and serves as a brake for neutrophil maturation in granulocyte lineage-specified cells through transcriptional regulation of lineage-specific transcription factors and RNA via altered messenger RNA splicing to reprogram intron retention.",

keywords = "Animals, CD4 Antigens, Cell Differentiation, Cell Lineage, DNA-Binding Proteins, Gene Expression Regulation, Mice, Mice, Knockout, RNA, Thymus Gland, Transcription Factors/genetics",

author = "Jayati Basu and Andre Olsson and Kyle Ferchen and Titerina, \{Elizaveta K.\} and Kashish Chetal and Emmanuelle Nicolas and Philip Czyzewicz and Dmitry Levchenko and Lu Ge and Xiang Hua and Grimes, \{H. Leighton\} and Nathan Salomonis and Kappes, \{Dietmar J.\}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2023",

month = aug,

doi = "10.1038/s41590-023-01549-3",

language = "English",

volume = "24",

pages = "1295--1307",

journal = "Nature Immunology",

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AU - Basu, Jayati

AU - Olsson, Andre

AU - Ferchen, Kyle

AU - Titerina, Elizaveta K.

AU - Chetal, Kashish

AU - Nicolas, Emmanuelle

AU - Czyzewicz, Philip

AU - Levchenko, Dmitry

AU - Ge, Lu

AU - Hua, Xiang

AU - Grimes, H. Leighton

AU - Salomonis, Nathan

AU - Kappes, Dietmar J.

PY - 2023/8

Y1 - 2023/8

N2 - The transcription factor ThPOK (encoded by Zbtb7b) is well known for its role as a master regulator of CD4 lineage commitment in the thymus. Here, we report an unexpected and critical role of ThPOK as a multifaceted regulator of myeloid lineage commitment, differentiation and maturation. Using reporter and knockout mouse models combined with single-cell RNA-sequencing, progenitor transfer and colony assays, we show that ThPOK controls monocyte-dendritic cell versus granulocyte lineage production during homeostatic differentiation, and serves as a brake for neutrophil maturation in granulocyte lineage-specified cells through transcriptional regulation of lineage-specific transcription factors and RNA via altered messenger RNA splicing to reprogram intron retention.

AB - The transcription factor ThPOK (encoded by Zbtb7b) is well known for its role as a master regulator of CD4 lineage commitment in the thymus. Here, we report an unexpected and critical role of ThPOK as a multifaceted regulator of myeloid lineage commitment, differentiation and maturation. Using reporter and knockout mouse models combined with single-cell RNA-sequencing, progenitor transfer and colony assays, we show that ThPOK controls monocyte-dendritic cell versus granulocyte lineage production during homeostatic differentiation, and serves as a brake for neutrophil maturation in granulocyte lineage-specified cells through transcriptional regulation of lineage-specific transcription factors and RNA via altered messenger RNA splicing to reprogram intron retention.

KW - Animals

KW - CD4 Antigens

KW - Cell Differentiation

KW - Cell Lineage

KW - DNA-Binding Proteins

KW - Gene Expression Regulation

KW - Mice

KW - Mice, Knockout

KW - RNA

KW - Thymus Gland

KW - Transcription Factors/genetics

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U2 - 10.1038/s41590-023-01549-3

DO - 10.1038/s41590-023-01549-3

M3 - Article

C2 - 37474652

SN - 1529-2908

VL - 24

SP - 1295

EP - 1307

JO - Nature Immunology

JF - Nature Immunology

IS - 8

ER -

ThPOK is a critical multifaceted regulator of myeloid lineage development

Abstract

Keywords

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New Life Science Study Findings Have Been Reported by Investigators at Fox Chase Cancer Center (Thpok Is a Critical Multifaceted Regulator of Myeloid Lineage Development)

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Laboratory Animal Facility

Transgenic Mouse Facility

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ThPOK is a critical multifaceted regulator of myeloid lineage development

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Press/Media

New Life Science Study Findings Have Been Reported by Investigators at Fox Chase Cancer Center (Thpok Is a Critical Multifaceted Regulator of Myeloid Lineage Development)

Equipment

Cell Sorting Facility

Laboratory Animal Facility

Transgenic Mouse Facility

Cite this