单细胞轨迹检测揭示了人类 B 细胞发育中的进展和调控协调。
Single-cell trajectory detection uncovers progression and regulatory coordination in human B cell development.
机构信息
Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA; Hematology and Oncology, Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
出版信息
Cell. 2014 Apr 24;157(3):714-25. doi: 10.1016/j.cell.2014.04.005.
Tissue regeneration is an orchestrated progression of cells from an immature state to a mature one, conventionally represented as distinctive cell subsets. A continuum of transitional cell states exists between these discrete stages. We combine the depth of single-cell mass cytometry and an algorithm developed to leverage this continuum by aligning single cells of a given lineage onto a unified trajectory that accurately predicts the developmental path de novo. Applied to human B cell lymphopoiesis, the algorithm (termed Wanderlust) constructed trajectories spanning from hematopoietic stem cells through to naive B cells. This trajectory revealed nascent fractions of B cell progenitors and aligned them with developmentally cued regulatory signaling including IL-7/STAT5 and cellular events such as immunoglobulin rearrangement, highlighting checkpoints across which regulatory signals are rewired paralleling changes in cellular state. This study provides a comprehensive analysis of human B lymphopoiesis, laying a foundation to apply this approach to other tissues and "corrupted" developmental processes including cancer.
组织再生是细胞从未成熟状态到成熟状态的有序进展，通常表现为不同的细胞亚群。这些离散阶段之间存在着连续的过渡细胞状态。我们结合了单细胞质量细胞术的深度和一种算法，该算法通过将给定谱系的单细胞排列到一个统一的轨迹上，从而利用这个连续体，该轨迹可以准确地从头预测发育路径。将该算法（称为 Wanderlust）应用于人类 B 细胞淋巴样发生，该算法构建了从造血干细胞到幼稚 B 细胞的轨迹。该轨迹揭示了 B 细胞祖细胞的新生部分，并将它们与发育提示的调节信号（包括 IL-7/STAT5）以及细胞事件（如免疫球蛋白重排）对齐，突出了调控信号在细胞状态变化时重新布线的检查点。这项研究对人类 B 细胞淋巴样发生进行了全面分析，为将这种方法应用于其他组织和“紊乱”的发育过程（包括癌症）奠定了基础。
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