Multispecies RNA tomography reveals regulators of hematopoietic stem cell birth in the embryonic aorta.
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IF: 25.476
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Cited by: 22
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Datasets
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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.

Keywords

Gene Expression
Spatial Transcriptomics
Tomo-seq

MeSH terms

Animals
Animals, Genetically Modified
Aorta
Cell Tracking
Chick Embryo
Embryo, Mammalian
Embryo, Nonmammalian
Gene Expression Regulation, Developmental
Hematopoiesis
Hematopoietic Stem Cells
Humans
Mice
RNA
Sequence Analysis, RNA
Single-Cell Analysis
Species Specificity
Stem Cell Niche
Tomography
Zebrafish

Authors

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

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