美国费城儿童医院Kai Tan等研究人员合作利用单细胞转录组学和蛋白质组成像，绘制了人类骨髓微环境的细胞生物地理图谱。相关论文于2024年5月6日在线发表在《细胞》杂志上。
研究人员利用单细胞RNA测序（scRNA-seq）分析了29325个非造血细胞，发现了九种转录不同的亚型。研究人员同时分析了53417个造血细胞，并预测了它们与非造血细胞亚群的相互作用。研究人员利用索引共同检测（CODEX）对120多万个细胞进行了空间分析。研究人员整合了scRNA-seq和CODEX数据，将预测的细胞信号传导与空间邻近性联系起来。这些分析揭示了早期骨髓造血的高氧动脉内膜邻近地区，以及早期造血干细胞和祖细胞（HSPC）的脂肪细胞定位。
研究人员利用CODEX图谱对新图像进行了注释，发现了间充质基质细胞（MSC）的扩增以及急性髓性白血病（AML）患者样本中，白血病胚泡和间充质基质细胞共同富集的空间邻域。这种空间分辨的人类骨髓多组学图谱为研究驱动造血的细胞相互作用提供了参考。
据了解，非造血细胞是造血的重要组成部分。然而，这些细胞在人类骨髓中的异质性和空间组织在很大程度上仍未得到表征。
附：英文原文
Title: Mapping the cellular biogeography of human bone marrow niches using single-cell transcriptomics and proteomic imaging
Author: Shovik Bandyopadhyay, Michael P. Duffy, Kyung Jin Ahn, Jonathan H. Sussman, Minxing Pang, David Smith, Gwendolyn Duncan, Iris Zhang, Jeffrey Huang, Yulieh Lin, Barbara Xiong, Tamjid Imtiaz, Chia-Hui Chen, Anusha Thadi, Changya Chen, Jason Xu, Melissa Reichart, Zachary Martinez, Caroline Diorio, Chider Chen, Vinodh Pillai, Oraine Snaith, Derek Oldridge, Siddharth Bhattacharyya, Ivan Maillard, Martin Carroll, Charles Nelson, Ling Qin, Kai Tan
Issue&Volume: 2024-05-06
Abstract: Non-hematopoietic cells are essential contributors to hematopoiesis. However, heterogeneity and spatial organization of these cells in human bone marrow remain largely uncharacterized. We used single-cell RNA sequencing (scRNA-seq) to profile 29,325 non-hematopoietic cells and discovered nine transcriptionally distinct subtypes. We simultaneously profiled 53,417 hematopoietic cells and predicted their interactions with non-hematopoietic subsets. We employed co-detection by indexing (CODEX) to spatially profile over 1.2 million cells. We integrated scRNA-seq and CODEX data to link predicted cellular signaling with spatial proximity. Our analysis revealed a hyperoxygenated arterio-endosteal neighborhood for early myelopoiesis, and an adipocytic localization for early hematopoietic stem and progenitor cells (HSPCs). We used our CODEX atlas to annotate new images and uncovered mesenchymal stromal cell (MSC) expansion and spatial neighborhoods co-enriched for leukemic blasts and MSCs in acute myeloid leukemia (AML) patient samples. This spatially resolved, multiomic atlas of human bone marrow provides a reference for investigation of cellular interactions that drive hematopoiesis.
DOI: 10.1016/j.cell.2024.04.013
Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00408-2