Polyclonal regeneration of mouse bone marrow endothelial cells after irradiative conditioning.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2024-10-25 DOI:10.1016/j.celrep.2024.114779

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

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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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照射调理后小鼠骨髓内皮细胞的多克隆再生。

骨髓内皮细胞（BM-ECs）是 BM 龛的重要组成部分，支持造血干细胞（HSCs）的功能。然而，造血干细胞移植的调理会对受者的骨髓内皮细胞造成损伤，并可能导致移植相关的发病率。在这里，我们研究了辐照调理后BM-EC再生的细胞和克隆机制。利用单细胞 RNA 测序、成像和流式细胞术，我们揭示了辐照应激再生过程中 BM-ECs 异质性池的变化。接着，我们开发了一种单细胞体外克隆生成试验，并证明所有的EC组分都有很大的潜力重新进入细胞周期并形成血管样结构。最后，我们利用 Rainbow 小鼠和基于机器学习的模型证明，辐照后 BM-ECs 的再生大多是多克隆的，并由 BM-ECs 的广泛部分驱动；然而，在再生的后期阶段，克隆间的细胞输出会有所不同。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.