Specification of the haematopoietic stem cell lineage: From blood-fated mesodermal angioblasts to haemogenic endothelium.

Semin Cell Dev Biol

MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK. Electronic address:

Published: July 2022

Haematopoietic stem and progenitor cells emerge from specialized haemogenic endothelial cells in select vascular beds during embryonic development. Specification and commitment to the blood lineage, however, occur before endothelial cells are endowed with haemogenic competence, at the time of mesoderm patterning and production of endothelial cell progenitors (angioblasts). Whilst early blood cell fate specification has long been recognized, very little is known about the mechanisms that induce endothelial cell diversification and progressive acquisition of a blood identity by a subset of these cells. Here, we review the endothelial origin of the haematopoietic system and the complex developmental journey of blood-fated angioblasts. We discuss how recent technological advances will be instrumental to examine the diversity of the embryonic anatomical niches, signaling pathways and downstream epigenetic and transcriptional processes controlling endothelial cell heterogeneity and blood cell fate specification. Ultimately, this will give essential insights into the ontogeny of the cells giving rise to haematopoietic stem cells, that may aid in the development of novel strategies for their in vitro production for clinical purposes.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.semcdb.2022.01.008DOI Listing

Publication Analysis

Top Keywords

haematopoietic stem
12
endothelial cell
12
endothelial cells
8
blood cell
8
cell fate
8
fate specification
8
cell
6
cells
6
endothelial
6
specification
4

Similar Publications

Receptor Interacting Serine/Threonine Kinase 1 (RIPK1) is widely expressed and integral to inflammatory and cell death responses. Autosomal recessive RIPK1-deficiency, due to biallelic loss of function mutations in RIPK1, is a rare inborn error of immunity (IEI) resulting in uncontrolled necroptosis, apoptosis and inflammation. Although hematopoietic stem cell transplantation (HSCT) has been suggested as a potential curative therapy, the extent to which disease may be driven by extra-hematopoietic effects of RIPK1-deficiency, which are non-amenable to HSCT, is not clear.

View Article and Find Full Text PDF

Background: There is emerging evidence for the role of exercise in optimising function, quality of life (QoL) and reducing hospital length-of-stay if commenced prior to undergoing autologous stem cell transplantation (ASCT). A local pilot study of a prehabilitation and rehabilitation intervention during ASCT for myeloma patients indicated promising results and was adapted to translate into local clinical care. The aim of this report is to describe an overview of a newly implemented physiotherapist-led exercise prehabilitation and rehabilitation service delivered as part of the myeloma ASCT pathway, and present real-world findings related to changes in function and QoL.

View Article and Find Full Text PDF

Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disorder leading to deleterious brain effects. While animal models suggested that MPS I severely affects white matter (WM), whole-brain diffusion tensor imaging (DTI) analysis was not performed due to MPS-related morphological abnormalities. 3T DTI data from 28 severe (MPS IH, treated with hematopoietic stem cell transplantation-HSCT), 16 attenuated MPS I patients (MPS IA) enrolled under the study protocol NCT01870375, and 27 healthy controls (HC) were analyzed using the free-water correction (FWC) method to resolve macrostructural partial volume effects and unravel differences in DTI metrics accounting for microstructural abnormalities.

View Article and Find Full Text PDF

Targeting KAT6A/B as a New Therapeutic Strategy for Cancer Therapy.

J Med Chem

January 2025

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.

The lysine acetyltransferase 6A (KAT6A, MOZ, MYST3) is a member of the MYST family of protein acetyltransferases, which are essential for different biological processes such as craniofacial, embryonic, stem cell development, and hematopoiesis. KAT6A is an oncogene in human acute myeloid leukemia (AML), and KAT6A overexpression in AML is associated with metastases and poor prognoses. Furthermore, KAT6A mutations play an important role in cancer formation and progression and result in therapeutic resistance in both hematopoietic malignancies and solid tumors.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!