In the spotlight: the role of TGFβ signalling in haematopoietic stem and progenitor cell emergence

Roshana Thambyrajah; Rui Monteiro

doi:10.1042/BST20210363

In the spotlight: the role of TGFβ signalling in haematopoietic stem and progenitor cell emergence

Roshana Thambyrajah, Rui Monteiro

Cancer and Genomic Sciences

Research output: Contribution to journal › Review article › peer-review

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Abstract

Haematopoietic stem and progenitor cells (HSPCs) sustain haematopoiesis by generating precise numbers of mature blood cells throughout the lifetime of an individual. In vertebrates, HSPCs arise during embryonic development from a specialised endothelial cell population, the haemogenic endothelium (HE). Signalling by the Transforming Growth Factor β (TGFβ) pathway is key to regulate haematopoiesis in the adult bone marrow, but evidence for a role in the formation of HSPCs has only recently started to emerge. In this review, we examine recent work in various model systems that demonstrate a key role for TGFβ signalling in HSPC emergence from the HE. The current evidence underpins two seemingly contradictory views of TGFβ function: as a negative regulator of HSPCs by limiting haematopoietic output from HE, and as a positive regulator, by programming the HE towards the haematopoietic fate. Understanding how to modulate the requirement for TGFβ signalling in HSC emergence may have critical implications for the generation of these cells in vitro for therapeutic use.

Original language	English
Article number	BST20210363
Pages (from-to)	703-712
Number of pages	10
Journal	Biochemical Society Transactions
Volume	50
Issue number	2
Early online date	14 Mar 2022
DOIs	https://doi.org/10.1042/BST20210363
Publication status	Published - Apr 2022

Bibliographical note

Funding Information:
R.T. is a recipient of BP2016(00021) and BP/MSCA 2018(00034) fellowship programs from the Generalitat de Catalunya/Marie Skłodowska-Curie Actions. R.M. is funded by the University of Birmingham and supported by Cancer Research UK [C17422/A25154].

Funding Information:
R.T. is a recipient of BP2016(00021) and BP/MSCA 2018(00034) fellowship programs from the Generalitat de Catalunya/Marie Sk?odowska-Curie Actions. R.M. is funded by the University of Birmingham and supported by Cancer Research UK [C17422/A25154].

Publisher Copyright:
© 2022 The Author(s)

Keywords

BMP
endothelial to haematopoietic transition
haemogenic endothelium
mouse models
TGFβ
zebrafish
Biochemistry
Signal Transduction
Transforming Growth Factor beta/metabolism
Hematopoietic Stem Cells/metabolism
Embryonic Development
Animals
Hematopoiesis
Cell Differentiation

ASJC Scopus subject areas

Biochemistry

Access to Document

10.1042/BST20210363Licence: Creative Commons: Attribution (CC BY)

ThambyrajahR2022spotlightFinal published version, 1.01 MBLicence: Creative Commons: Attribution (CC BY)

Defective replisome disassembly in cancer development
Gambus, A.
Cancer Research Uk
1/02/19 → 30/09/19
Project: Research
Modelling the earliest events in acute myeloid leukemia development
Bonifer, C.
Cancer Research Uk
1/06/18 → 31/03/20
Project: Research
Establishing a new model of TIL recruitment and retention using photoconvertible mice.
Withers, D.
Cancer Research Uk
1/05/18 → 31/12/18
Project: Research

Cite this

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abstract = "Haematopoietic stem and progenitor cells (HSPCs) sustain haematopoiesis by generating precise numbers of mature blood cells throughout the lifetime of an individual. In vertebrates, HSPCs arise during embryonic development from a specialised endothelial cell population, the haemogenic endothelium (HE). Signalling by the Transforming Growth Factor β (TGFβ) pathway is key to regulate haematopoiesis in the adult bone marrow, but evidence for a role in the formation of HSPCs has only recently started to emerge. In this review, we examine recent work in various model systems that demonstrate a key role for TGFβ signalling in HSPC emergence from the HE. The current evidence underpins two seemingly contradictory views of TGFβ function: as a negative regulator of HSPCs by limiting haematopoietic output from HE, and as a positive regulator, by programming the HE towards the haematopoietic fate. Understanding how to modulate the requirement for TGFβ signalling in HSC emergence may have critical implications for the generation of these cells in vitro for therapeutic use.",

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In the spotlight: the role of TGFβ signalling in haematopoietic stem and progenitor cell emergence

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

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Projects

Defective replisome disassembly in cancer development

Modelling the earliest events in acute myeloid leukemia development

Establishing a new model of TIL recruitment and retention using photoconvertible mice.

Cite this