Multispecies RNA tomography reveals regulators of hematopoietic stem cell birth in the embryonic aorta

Laurent Yvernogeau, Anna Klaus, Joris Maas, Ismaël Morin-Poulard, Bart Weijts, Stefan Schulte-Merker, Eugene Berezikov, Jan Philipp Junker, Catherine Robin*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    33 Citations (Scopus)
    55 Downloads (Pure)

    Abstract

    The defined location of a stem cell within a niche regulates its fate, behavior, and molecular identity via a complex extrinsic regulation that is far from being fully elucidated. To explore the molecular characteristics and key components of the aortic microenvironment, where the first hematopoietic stem cells are generated during development, we performed genome-wide RNA tomography sequencing on zebrafish, chicken, mouse, and human embryos. The resulting anterior-posterior and dorsal-ventral transcriptional maps provided a powerful resource for exploring genes and regulatory pathways active in the aortic microenvironment. By performing interspecies comparative RNA sequencing analyses and functional assays, we explored the complexity of the aortic microenvironment landscape and the fine-tuning of various factors interacting to control hematopoietic stem cell generation, both in time and space in vivo, including the ligand-receptor couple ADM-RAMP2 and SVEP1. Understanding the regulatory function of the local environment will pave the way for improved stem cell production in vitro and clinical cell therapy.

    Original languageEnglish
    Pages (from-to)831-844
    Number of pages25
    JournalBlood
    Volume136
    Issue number7
    Early online date2020
    DOIs
    Publication statusPublished - 13-Aug-2020

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