美国哈佛医学院Allon M. Klein等研究人员合作利用谱系追踪的转录图谱将分化过程中的状态与命运联系起来。该项研究成果2020年1月23日在线发表在《科学》上。

Title: Lineage tracing on transcriptional landscapes links state to fate during differentiation

Author: Caleb Weinreb, Alejo Rodriguez-Fraticelli, Fernando D. Camargo, Allon M. Klein

Issue&Volume: 2020/01/23

Abstract: A challenge in biology is to associate molecular differences among progenitor cells with their capacity to generate mature cell types. Here, we use expressed DNA barcodes to clonally trace transcriptomes over time and applied this to study fate determination in hematopoiesis. We identify states of primed fate potential and locate them on a continuous transcriptional landscape. We identify two routes of monocyte differentiation that leave an imprint on mature cells. Yet analysis of sister cells also reveals cells to have intrinsic fate biases not detectable by single-cell RNA sequencing. Finally, we benchmark computational methods of dynamic inference from single-cell snapshots, showing that fate choice occurs earlier than is detected by state-of the-art algorithms, and that cells progress steadily through pseudotime with precise and consistent dynamics.

DOI: 10.1126/science.aaw3381

Source: https://science.sciencemag.org/content/early/2020/01/22/science.aaw3381