Murine AGM single-cell profiling identifies a continuum of hemogenic endothelium differentiation marked by ACE
Autor: | Georges Lacaud, Pierre Savatier, Renaud Mevel, Syed Murtuza Baker, Irene Aksoy, Wen Hao Neo, Rahima Patel, Valerie Kouskoff, Magnus Rattray, Laura Fontenille, Roshana Thambyrajah, Nam Do Khoa, Muhammad Zaki Hidayatullah Fadlullah, Michael Lie-A-Ling |
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Rok vydání: | 2022 |
Předmět: |
Hemangioblasts
Immunology Biology Biochemistry Mice chemistry.chemical_compound Dorsal aorta medicine Animals Zebrafish Hemogenic endothelium Hematopoietic Stem Cells/cytology Manchester Cancer Research Centre ResearchInstitutes_Networks_Beacons/mcrc Mesonephros/cytology Mesenchymal stem cell Cell Differentiation Cell Biology Hematology Embryo Mammalian Hematopoietic Stem Cells Hematopoiesis Cell biology Transplantation Haematopoiesis Embryo Mammalian/cytology medicine.anatomical_structure RUNX1 chemistry Mesonephros Bone marrow Hemangioblasts/cytology Single-Cell Analysis Stem cell Transcriptome |
Zdroj: | Fadlullah, M Z H, Neo, W H, Lie-a-ling, M, Thambyrajah, R, Patel, R, Mevel, R, Aksoy, I, Do Khoa, N, Savatier, P, Fontenille, L, Baker, S M, Rattray, M, Kouskoff, V & Lacaud, G 2022, ' Murine AGM single-cell profiling identifies a continuum of hemogenic endothelium differentiation marked by ACE ', Blood, vol. 139, no. 3, pp. 343-356 . https://doi.org/10.1182/blood.2020007885, https://doi.org/10.1182/blood.2020007885 |
ISSN: | 1528-0020 0006-4971 |
Popis: | In vitro generation and expansion of hematopoietic stem cells (HSCs) holds great promise for the treatment of any ailment that relies on bone marrow or blood transplantation. To achieve this, it is essential to resolve the molecular and cellular pathways that govern HSC formation in the embryo. HSCs first emerge in the aorta-gonad-mesonephros (AGM) region, where a rare subset of endothelial cells, hemogenic endothelium (HE), undergoes an endothelial-to-hematopoietic transition (EHT). Here, we present full-length single-cell RNA sequencing (scRNA-seq) of the EHT process with a focus on HE and dorsal aorta niche cells. By using Runx1b and Gfi1/1b transgenic reporter mouse models to isolate HE, we uncovered that the pre-HE to HE continuum is specifically marked by angiotensin-I converting enzyme (ACE) expression. We established that HE cells begin to enter the cell cycle near the time of EHT initiation when their morphology still resembles endothelial cells. We further demonstrated that RUNX1 AGM niche cells consist of vascular smooth muscle cells and PDGFRa+ mesenchymal cells and can functionally support hematopoiesis. Overall, our study provides new insights into HE differentiation toward HSC and the role of AGM RUNX1+ niche cells in this process. Our expansive scRNA-seq datasets represents a powerful resource to investigate these processes further. |
Databáze: | OpenAIRE |
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