Inferring Gene Networks in Bone Marrow Hematopoietic Stem Cell-Supporting Stromal Niche Populations

iScience

Nadir Sella¹  Hervé Isambert¹  Thierry Jaffredo²  Charles Durand³  Vincent Cabeli³  Laura Coquelin⁴  Nathalie Chevallier⁴  Pierre Charbord⁴  Laurence Petit⁵  Robert A.J. Oostendorp⁵  Christophe Desterke⁶ 

[1] Paris 75005, France;Clinic and Polyclinic for Internal Medicine III, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany;IMRB U955-E10, INSERM, Unité d'Ingenierie et de Thérapie Cellulaire- EFS, Université Paris-EST, Créteil, France;Institut Curie, PSL Research University, CNRS UMR168, Paris, France;Sorbonne Université, UPMC Université Paris 06, IBPS, CNRS UMR7622, Inserm U 1156, Laboratoire de Biologie du Développement;Université Paris Sud, Hôpital Paul Brousse, Villejuif, France;

关键词: Cell Biology;    Stem Cells Research;    Bioinformatics;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: The cardinal property of bone marrow (BM) stromal cells is their capacity to contribute to hematopoietic stem cell (HSC) niches by providing mediators assisting HSC functions. In this study we first contrasted transcriptomes of stromal cells at different developmental stages and then included large number of HSC-supportive and non-supportive samples. Application of a combination of algorithms, comprising one identifying reliable paths and potential causative relationships in complex systems, revealed gene networks characteristic of the BM stromal HSC-supportive capacity and of defined niche populations of perivascular cells, osteoblasts, and mesenchymal stromal cells. Inclusion of single-cell transcriptomes enabled establishing for the perivascular cell subset a partially oriented graph of direct gene-to-gene interactions. As proof of concept we showed that R-spondin-2, expressed by the perivascular subset, synergized with Kit ligand to amplify ex vivo hematopoietic precursors. This study by identifying classifiers and hubs constitutes a resource to unravel candidate BM stromal mediators.

【 授权许可】

Unknown