Back to research groups
The Robin group studies the cellular and molecular mechanisms that lead to the production and expansion of hematopoietic stem cells during embryonic development.
Hematopoietic stem cells (HSCs) are self-renewing multipotent cells that produce all blood cell types during the entire life of an individual. Hence, they are the only cell type that can be used to replenish the bone marrow in patients with blood-related disorders. One major challenge in the field of stem cell research is to generate large quantities of these very rare cells in vitro for research and clinical use. This is extremely difficult at present because all steps leading to HSC generation in vivo, and the precise role of the supportive surrounding microenvironment, are far from been elucidated yet. The overall research goal of the lab is to elucidate the cellular and molecular events leading to HSC production and expansion during embryonic development. We notably focus on understanding the origin of HSCs during embryonic development, the mechanisms implicated in HSC generation and expansion, the composition and function of the different HSC niches during ontogeny, and the cellular and molecular signature of HSCs and precursors.
All HSCs are generated during embryonic development from specialized endothelial cells endowed with a hemogenic potential. We and others have shown that hemogenic endothelial cells are present in the aorta where they generate numerous Intra-Aortic Hematopoietic Clusters (IAHCs) that contain very few HSCs. Therefore, the identity of most IAHC cells is unknown. We are interested in identifying all cell types present in IAHCs, and elucidating the successive steps leading to IAHC and HSC formation, at the cellular and molecular levels.
Our research aims to uncover the essential factors that regulate embryonic HSC production. At mouse embryonic day (E)10.5, HSCs are part of intra-aortic hematopoietic clusters (IAHCs) that are tightly attached to the aortic endothelium. We recently established a novel experimental imaging set-up to show the dynamic formation of HSCs directly in the aorta of the mouse embryo. During the endothelial into hematopoietic transition (EHT), we observed intense cellular movements and surface membrane modifications, highlighting important roles for cell adhesion molecules and microtubule (MT) cytoskeleton rearrangement. We aim to understand the basic biomechanics of embryonic HSC formation with a focus on MT regulatory proteins. These proteins are especially involved in cell polarity regulation, (asymmetric) cell division, adhesion, and migration. New transgenic mouse lines will also be generated to study IAHC formation in the mouse embryo.
HSC emergence mainly occurs in the ventral aspect of the embryo aorta (zebrafish, chicken, mouse and human) and is tightly controlled in time and space by regulatory signals emitted by the surrounding microenvironment. The precise, specific and well-defined localization of HSC emergence in the aorta of the aforementioned species make all these models powerful tools to trigger the molecular signals coming from the surrounding tissues and restricting hematopoietic activity to specific areas. Using state-of-the-art technology, we aim to decipher genes that are (differentially) expressed in specific regions of the aorta during HSC generation. The comparison of all species will also to unravel conserved molecular pathways involved in the regulation of the first HSC generated during embryonic development.
The anatomical site of mammalian HSC origin remains controversial in mammals because the blood is already circulating at the time of HSC detection (leading to the possibility of cell exchange between tissues). To solve this fundamental question, we are currently developing novel and challenging in vivo embryo rescue assay.
Yvernogeau L, Robin C.
Boisset JC, Clapes T, Klaus A, Papazian N, Onderwater J, Mommaas-Kienhuis M, Cupedo T, Robin C.
Drabek K, Gutiérrez L, Vermeij M, Clapes T, Patel SR, Boisset JC, van Haren J, Pereira AL, Liu Z, Akinci U, Nikolic T, van Ijcken W, van den Hout M, Meinders M, Melo C, Sambade C, Drabek D, Hendriks RW, Philipsen S, Mommaas M, Grosveld F, Maiato H, Italiano JE Jr, Robin C, Galjart N.
Boisset JC, Andrieu-Soler C, van Cappellen W, Clapes T, Robin C.
Boisset JC, van Cappellen W, Andrieu-Soler C, Galjart N, Dzierzak E, Robin C.
Robin C, Bollerot K, Mendes S, Haak E, Crisan M, Cerisoli F, Lauw I, Kaimakis P, Jorna R, Vermeulen M, Kayser M, van der Linden R, Imanirad P, Verstegen M, Nawaz-Yousaf H, Papazian N, Steegers E, Cupedo T, Dzierzak E.
Robin C, Ottersbach K, Durand C, Peeters M, Vanes L, Tybulewicz V, Dzierzak E.
de Bruijn MF*, Ma X*, Robin C*, Ottersbach K, Sanchez MJ, Dzierzak E.
Robin C, Pflumio F, Vainchenker W, Coulombel L.
Catherine Robin is group leader at the Hubrecht Institute and is also appointed at the University Medical Center Utrecht. Her group focuses on the establishment of the hematopoietic system during embryonic development. They are particularly interested in better understanding how the first hematopoietic stem cells, the very rare cells at the foundation of the entire adult blood system, are generated and regulated during embryonic development. To answer these fundamental questions, the Robin group uses state-of-the-art technology and methods, including time-lapse live confocal imaging, in vivo transplantation and single-cell RNA sequencing.
Scientific training and positions
Current other activities
Speakers and organisers: https://www.embl.de/training/events/2018/EHT18-01/speakers_organisers_gallery/index.html
More information: http://www.embl.de/training/events/2016/EHT16-01/registration/index.html