荷兰乌得勒支大学医学中心Jop Kind研究团队利用MAbID对主要染色质类型进行组合单细胞分析。该项研究成果于2023年12月4日在线发表在《自然—方法学》杂志上。

研究人员介绍了一种通过条形码识别多重抗体的方法（MAbID），这是一种对组蛋白修饰和染色质结合蛋白进行组合基因组分析的方法。MAbID利用抗体-DNA偶联物在表位的基因组位置整合条形码，从而使多种抗体的联合孵育能够同时揭示许多表观遗传标记物的分布。研究人员利用MAbID分析了主要染色质类型，并在不损失单个数据质量的情况下进行了多重测量。

此外，研究人员还对小鼠骨髓单细胞和小鼠体外分化过程中的六个表位进行了联合测量，并捕捉到了多因素染色质状态的相关变化。因此，MAbID有助于深入了解基因调控机制之间的相互作用，特别是在低投入样本和单细胞中。

据悉，基因表达程序是众多调控因子共同作用的结果。要了解基因调控，研究它们的合作作用模式势在必行，但在一个样本中同时测量这些因子却极具挑战性。

附：英文原文

Title: Combinatorial single-cell profiling of major chromatin types with MAbID

Author: Lochs, Silke J. A., van der Weide, Robin H., de Luca, Kim L., Korthout, Tessy, van Beek, Ramada E., Kimura, Hiroshi, Kind, Jop

Issue&Volume: 2023-12-04

Abstract: Gene expression programs result from the collective activity of numerous regulatory factors. Studying their cooperative mode of action is imperative to understand gene regulation, but simultaneously measuring these factors within one sample has been challenging. Here we introduce Multiplexing Antibodies by barcode Identification (MAbID), a method for combinatorial genomic profiling of histone modifications and chromatin-binding proteins. MAbID employs antibody–DNA conjugates to integrate barcodes at the genomic location of the epitope, enabling combined incubation of multiple antibodies to reveal the distributions of many epigenetic markers simultaneously. We used MAbID to profile major chromatin types and multiplexed measurements without loss of individual data quality. Moreover, we obtained joint measurements of six epitopes in single cells of mouse bone marrow and during mouse in vitro differentiation, capturing associated changes in multifactorial chromatin states. Thus, MAbID holds the potential to gain unique insights into the interplay between gene regulatory mechanisms, especially for low-input samples and in single cells.

DOI: 10.1038/s41592-023-02090-9

Source: https://www.nature.com/articles/s41592-023-02090-9