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Analysis of endothelial-to-haematopoietic transition at the single cell level identifies cell cycle regulation as a driver of differentiation
BACKGROUND: Haematopoietic stem cells (HSCs) first arise during development in the aorta-gonad-mesonephros (AGM) region of the embryo from a population of haemogenic endothelial cells which undergo endothelial-to-haematopoietic transition (EHT). Despite the progress achieved in recent years, the mol...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329542/ https://www.ncbi.nlm.nih.gov/pubmed/32611441 http://dx.doi.org/10.1186/s13059-020-02058-4 |
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author | Canu, Giovanni Athanasiadis, Emmanouil Grandy, Rodrigo A. Garcia-Bernardo, Jose Strzelecka, Paulina M. Vallier, Ludovic Ortmann, Daniel Cvejic, Ana |
author_facet | Canu, Giovanni Athanasiadis, Emmanouil Grandy, Rodrigo A. Garcia-Bernardo, Jose Strzelecka, Paulina M. Vallier, Ludovic Ortmann, Daniel Cvejic, Ana |
author_sort | Canu, Giovanni |
collection | PubMed |
description | BACKGROUND: Haematopoietic stem cells (HSCs) first arise during development in the aorta-gonad-mesonephros (AGM) region of the embryo from a population of haemogenic endothelial cells which undergo endothelial-to-haematopoietic transition (EHT). Despite the progress achieved in recent years, the molecular mechanisms driving EHT are still poorly understood, especially in human where the AGM region is not easily accessible. RESULTS: In this study, we take advantage of a human pluripotent stem cell (hPSC) differentiation system and single-cell transcriptomics to recapitulate EHT in vitro and uncover mechanisms by which the haemogenic endothelium generates early haematopoietic cells. We show that most of the endothelial cells reside in a quiescent state and progress to the haematopoietic fate within a defined time window, within which they need to re-enter into the cell cycle. If cell cycle is blocked, haemogenic endothelial cells lose their EHT potential and adopt a non-haemogenic identity. Furthermore, we demonstrate that CDK4/6 and CDK1 play a key role not only in the transition but also in allowing haematopoietic progenitors to establish their full differentiation potential. CONCLUSION: We propose a direct link between the molecular machineries that control cell cycle progression and EHT. |
format | Online Article Text |
id | pubmed-7329542 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-73295422020-07-02 Analysis of endothelial-to-haematopoietic transition at the single cell level identifies cell cycle regulation as a driver of differentiation Canu, Giovanni Athanasiadis, Emmanouil Grandy, Rodrigo A. Garcia-Bernardo, Jose Strzelecka, Paulina M. Vallier, Ludovic Ortmann, Daniel Cvejic, Ana Genome Biol Research BACKGROUND: Haematopoietic stem cells (HSCs) first arise during development in the aorta-gonad-mesonephros (AGM) region of the embryo from a population of haemogenic endothelial cells which undergo endothelial-to-haematopoietic transition (EHT). Despite the progress achieved in recent years, the molecular mechanisms driving EHT are still poorly understood, especially in human where the AGM region is not easily accessible. RESULTS: In this study, we take advantage of a human pluripotent stem cell (hPSC) differentiation system and single-cell transcriptomics to recapitulate EHT in vitro and uncover mechanisms by which the haemogenic endothelium generates early haematopoietic cells. We show that most of the endothelial cells reside in a quiescent state and progress to the haematopoietic fate within a defined time window, within which they need to re-enter into the cell cycle. If cell cycle is blocked, haemogenic endothelial cells lose their EHT potential and adopt a non-haemogenic identity. Furthermore, we demonstrate that CDK4/6 and CDK1 play a key role not only in the transition but also in allowing haematopoietic progenitors to establish their full differentiation potential. CONCLUSION: We propose a direct link between the molecular machineries that control cell cycle progression and EHT. BioMed Central 2020-07-01 /pmc/articles/PMC7329542/ /pubmed/32611441 http://dx.doi.org/10.1186/s13059-020-02058-4 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Canu, Giovanni Athanasiadis, Emmanouil Grandy, Rodrigo A. Garcia-Bernardo, Jose Strzelecka, Paulina M. Vallier, Ludovic Ortmann, Daniel Cvejic, Ana Analysis of endothelial-to-haematopoietic transition at the single cell level identifies cell cycle regulation as a driver of differentiation |
title | Analysis of endothelial-to-haematopoietic transition at the single cell level identifies cell cycle regulation as a driver of differentiation |
title_full | Analysis of endothelial-to-haematopoietic transition at the single cell level identifies cell cycle regulation as a driver of differentiation |
title_fullStr | Analysis of endothelial-to-haematopoietic transition at the single cell level identifies cell cycle regulation as a driver of differentiation |
title_full_unstemmed | Analysis of endothelial-to-haematopoietic transition at the single cell level identifies cell cycle regulation as a driver of differentiation |
title_short | Analysis of endothelial-to-haematopoietic transition at the single cell level identifies cell cycle regulation as a driver of differentiation |
title_sort | analysis of endothelial-to-haematopoietic transition at the single cell level identifies cell cycle regulation as a driver of differentiation |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329542/ https://www.ncbi.nlm.nih.gov/pubmed/32611441 http://dx.doi.org/10.1186/s13059-020-02058-4 |
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