Oatley, Morgan and Vargel Bölükbası, Özge and Svensson, Valentine and Shvartsman, Maya and Ganter, Kerstin and Zirngibl, Katharina and Pavlovich, Polina V. and Milchevskaya, Vladislava and Foteva, Vladimira and Natarajan, Kedar N. and Baying, Bianka and Benes, Vladimir and Patil, Kiran R. and Teichmann, Sarah A. and Lancrin, Christophe (2018) Single-cell transcriptomics identifies CD44 as a new marker and regulator of haematopoietic stem cells development. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20181030-105949740
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Abstract
The endothelial to haematopoietic transition (EHT) is the process whereby haemogenic endothelium differentiates into haematopoietic stem and progenitor cells (HSPCs). The intermediary steps of this process are unclear, in particular the identity of endothelial cells that give rise to HSPCs is unknown. Using single-cell transcriptome analysis and antibody screening we identified CD44 as a new marker of EHT enabling us to isolate robustly the different stages of EHT in the aorta gonad mesonephros (AGM) region. This allowed us to provide a very detailed phenotypical and transcriptional profile for haemogenic endothelial cells, characterising them with high expression of genes related to Notch signalling, TGFbeta/BMP antagonists (Smad6, Smad7 and Bmper) and a downregulation of genes related to glycolysis and the TCA cycle. Moreover, we demonstrated that by inhibiting the interaction between CD44 and its ligand hyaluronan we could block EHT, identifying a new regulator of HSPC development.
| Item Type: | Report or Paper (Discussion Paper) | ||||||||||||
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| Additional Information: | The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. bioRxiv preprint first posted online Jun. 6, 2018. We thank Kalina Stantcheva and Cora Chadick (EMBL Rome FACS Facility, Italy) for cell sorting; Andreas Buness (EMBL Rome Bioinformatics Services, Italy) and Tallulah Andrews (Wellcome Trust Sanger Institute, UK) for help with bioinformatics analysis; Paul Collier, (EMBL Genomics Core Facility, Germany) for bulk RNA-seq; Gisela Luz (Patil Group, EMBL, Germany) for scientific illustration; Inke Nathke (University of Dundee, Scotland), Paul Heppenstall (EMBL, Italy) and Alexander Aulehla (EMBL, Germany) for fruitful scientific discussions. The European Molecular Biology Laboratory and the Wellcome Trust supported this work. | ||||||||||||
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| Record Number: | CaltechAUTHORS:20181030-105949740 | ||||||||||||
| Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20181030-105949740 | ||||||||||||
| Official Citation: | Single-cell transcriptomics identifies CD44 as a new marker and regulator of haematopoietic stem cells development. Morgan Oatley, Ozge Vargel Bolukbasi, Valentine Svensson, Maya Shvartsman, Kerstin Ganter, Katharina Zirngibl, Polina V Pavlovich, Vladislava Milchevskaya, Vladimira Foteva, Kedar N. Natarajan, Bianka Baying, Vladimir Benes, Kiran Raosaheb Patil, Sarah A. Teichmann, Christophe Lancrin. bioRxiv 338178; doi: https://doi.org/10.1101/338178 | ||||||||||||
| Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||||||
| ID Code: | 90502 | ||||||||||||
| Collection: | CaltechAUTHORS | ||||||||||||
| Deposited By: | Tony Diaz | ||||||||||||
| Deposited On: | 30 Oct 2018 18:17 | ||||||||||||
| Last Modified: | 03 Oct 2019 20:25 |
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