Polyclonal Regeneration of Mouse Bone Marrow Endothelial Cells After Irradiative Conditioning

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2024 Nov 3

PMID 39489938

Authors

Izabella Skulimowska

Jan Morys

Justyna Sosniak

Monika Gonka

Gunsagar Gulati

Rahul Sinha

Kacper Kowalski

Sylwester Mosiolek

Irving L Weissman

Alicja Jozkowicz

Agata Szade

Krzysztof Szade

Affiliations

Soon will be listed here.

Abstract

Bone marrow endothelial cells (BM-ECs) are the essential components of the BM niche and support the function of hematopoietic stem cells (HSCs). However, conditioning for HSC transplantation causes damage to the recipients' BM-ECs and may lead to transplantation-related morbidity. Here, we investigated the cellular and clonal mechanisms of BM-EC regeneration after irradiative conditioning. Using single-cell RNA sequencing, imaging, and flow cytometry, we revealed how the heterogeneous pool of BM-ECs changes during regeneration from irradiation stress. Next, we developed a single-cell in vitro clonogenic assay and demonstrated that all EC fractions hold a high potential to reenter the cell cycle and form vessel-like structures. Finally, we used Rainbow mice and a machine-learning-based model to show that the regeneration of BM-ECs after irradiation is mostly polyclonal and driven by the broad fraction of BM-ECs; however, the cell output among clones varies at later stages of regeneration.

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