In vivo generation of haematopoietic stem/progenitor cells from bone marrow-derived haemogenic endothelium.
Laurent YvernogeauRodolphe GautierLaurence PetitHanane KhouryFrederic RelaixVanessa RibesHelen SangPierre CharbordMichèle SouyriCatherine RobinThierry JaffredoPublished in: Nature cell biology (2019)
It is well established that haematopoietic stem and progenitor cells (HSPCs) are generated from a transient subset of specialized endothelial cells termed haemogenic, present in the yolk sac, placenta and aorta, through an endothelial-to-haematopoietic transition (EHT). HSPC generation via EHT is thought to be restricted to the early stages of development. By using experimental embryology and genetic approaches in birds and mice, respectively, we document here the discovery of a bone marrow haemogenic endothelium in the late fetus/young adult. These cells are capable of de novo producing a cohort of HSPCs in situ that harbour a very specific molecular signature close to that of aortic endothelial cells undergoing EHT or their immediate progenies, i.e., recently emerged HSPCs. Taken together, our results reveal that HSPCs can be generated de novo past embryonic stages. Understanding the molecular events controlling this production will be critical for devising innovative therapies.
Keyphrases
- endothelial cells
- bone marrow
- young adults
- aortic valve
- nitric oxide
- mesenchymal stem cells
- high glucose
- induced apoptosis
- genome wide
- pulmonary artery
- small molecule
- cell cycle arrest
- vascular endothelial growth factor
- palliative care
- high throughput
- single cell
- left ventricular
- dna methylation
- gene expression
- cell death
- endoplasmic reticulum stress
- type diabetes
- metabolic syndrome
- adipose tissue
- pulmonary hypertension
- copy number
- pulmonary arterial hypertension
- signaling pathway