德国癌症研究中心Hans-Reimer Rodewald和Thomas Hofer研究组合作取得最新进展。他们过PolyloxExpress条形码解析了造血干细胞（HSC）克隆命运和单细胞转录组。相关论文于2020年8月11日发表在《细胞-干细胞》杂志上。

为了获得有关同一细胞中fateplus转录组的信息，他们开发了PolyloxExpress等位基因，可实现Cre重组酶依赖的RNA原位编码。将命运与单个HSC转录组联系起来提供了鉴定HSC命运的转录特征所需的信息，这在单独的单个HSC转录组中并不明显。他们发现分化不活跃、多谱系和谱系受限的HSC克隆位于造血细胞转录全图谱的不同区域中。分化不活跃的HSC克隆更接近转录轨迹的起源，但它们没有静态基因为标志。

命运特定的基因特征暗示了克隆的HSC命运的一致性，并且向短寿命谱系祖细胞输出的HSC表明，HSC命运随着时间的推移是稳定的。这些在生理条件下对命运和转录组的综合分析，可能为鉴定HSC命运的分子决定因素铺平道路。

据介绍，谱系追踪揭示了HSC命运，而单细胞RNA测序鉴定了HSC转录组的快照。

附：英文原文

Title: Resolving Fates and Single-Cell Transcriptomes of Hematopoietic Stem Cell Clones by PolyloxExpress Barcoding

Author: Weike Pei, Fuwei Shang, Xi Wang, Ann-Kathrin Fanti, Alessandro Greco, Katrin Busch, Kay Klapproth, Qin Zhang, Claudia Quedenau, Sascha Sauer, Thorsten B. Feyerabend, Thomas Hfer, Hans-Reimer Rodewald

Issue&Volume: 2020-08-11

Abstract: Lineage tracing reveals hematopoietic stem cell (HSC) fates, while single-cell RNAsequencing identifies snapshots of HSC transcriptomes. To obtain information on fateplus transcriptome in the same cell, we developed the PolyloxExpress allele, enabling Cre-recombinase-dependent RNA barcoding in situ. Linking fates to single HSC transcriptomes provided the information required toidentify transcriptional signatures of HSC fates, which were not apparent in single-HSCtranscriptomes alone. We find that differentiation-inactive, multilineage, and lineage-restrictedHSC clones reside in distinct regions of the transcriptional landscape of hematopoiesis.Differentiation-inactive HSC clones are closer to the origin of the transcriptionaltrajectory, yet they are not characterized by a quiescent gene signature. Fate-specificgene signatures imply coherence of clonal HSC fates, and HSC output toward short-livedlineage progenitors indicates stability of HSC fates over time. These combined analysesof fate and transcriptome under physiological conditions may pave the way toward identifyingmolecular determinants of HSC fates.

DOI: 10.1016/j.stem.2020.07.018

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30356-8