TY - JOUR
T1 - Multispecies RNA tomography reveals regulators of hematopoietic stem cell birth in the embryonic aorta
AU - Yvernogeau, Laurent
AU - Klaus, Anna
AU - Maas, Joris
AU - Morin-Poulard, Ismaël
AU - Weijts, Bart
AU - Schulte-Merker, Stefan
AU - Berezikov, Eugene
AU - Junker, Jan Philipp
AU - Robin, Catherine
N1 - Funding Information:
The authors thank the laboratory members for helpful discussion and Carla Kroon-Veenboer and Rutger Wielink, in particular, for technical help; Alexander van Oudenaarden for very helpful discussions at the beginning of the project; Jacqueline Deschamps and Jean-Charles Boisset for useful comments on the manuscript; Romualdo Ciau-Uitz (from Roger Patient's laboratory) for kindly sharing zebrafish ISH probes; the Animal Facility for mouse and zebrafish care and the Optical Imaging Center for confocal microscope access (Hubrecht Institute); Stefan van der Elst (Hubrecht Institute) for help with cell sorting; Mauro Muraro for technical help and advice (Single Cell Discoveries bv); the Utrecht Sequencing Facility (USF), subsidized by the University Medical Center Utrecht, Hubrecht Institute, and Utrecht University; the E.B. laboratory for improving the chicken genome annotation; Kelly McNagny (Vancouver, BC, Canada) for the anti-chicken MEP21 supernatant; and Tom Cupedo (Erasmus MC, Rotterdam, The Netherlands) and Susana Chuva de Sousa Lopes (LUMC, Leiden, The Netherlands) for providing human tissue samples.
Funding Information:
This work was supported in the C.R. laboratory by a European Research Council grant (ERC; project number 220-H75001EU/HSCOrigin-309361), a TOP-subsidy from Netherlands Organization for Scientific Research (NWO)/ZonMw (912.15.017), and the UMC Utrecht “Regenerative Medicine & Stem Cells” priority research program.
Publisher Copyright:
© 2020 by The American Society of Hematology
PY - 2020/8/13
Y1 - 2020/8/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85089614154&partnerID=8YFLogxK
U2 - 10.1182/blood.2019004446
DO - 10.1182/blood.2019004446
M3 - Article
C2 - 32457985
AN - SCOPUS:85089614154
SN - 0006-4971
VL - 136
SP - 831
EP - 844
JO - Blood
JF - Blood
IS - 7
ER -