法国里昂大学F. Lavial和A. Huyghe共同合作近期取得重要工作进展，他们最新研究揭示，重编程和致癌转化的比较路线图确定Bcl11b和Atoh8是广泛的细胞可塑性调节因子。这一研究成果2022年9月8日在线发表于《自然细胞生物学》上。

研究人员以单细胞分辨率对重编程（通过Oct4/Sox2/Klf4/c-Myc）和转化（通过Ras/c-Myc）的细胞轨迹进行去卷积，并揭示这两个过程在它们分叉之前是如何相交的。这种方法使他们将转录因子Bcl11b确定为细胞命运变化的广泛调节因子，以及捕获在重编程和转化过程中同时出现的早期细胞中间体的相关标记。这些中间体的多组学特征揭示了一个限制重编程、转化和转分化的c-Myc/Atoh8/Sfrp1调节轴。从机制上讲，研究人员发现Atoh8通过结合特定的增强子网络来抑制细胞可塑性，与细胞身份无关。这项研究提供了对再生和癌症生物学的细胞可塑性和特性的分区控制的见解。

据介绍，细胞可塑性和身份的协调变化对多能性重编程和致癌转化至关重要。然而，这些错综复杂的变化背后所发生的一系列事件却从未被比较剖析过。

附：英文原文

Title: Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity

Author: Huyghe, A., Furlan, G., Schroeder, J., Cascales, E., Trajkova, A., Ruel, M., Stder, F., Larcombe, M., Yang Sun, Y. Bo, Mugnier, F., De Matteo, L., Baygin, A., Wang, J., Yu, Y., Rama, N., Gibert, B., Kielbassa, J., Tonon, L., Wajda, P., Gadot, N., Brevet, M., Siouda, M., Mulligan, P., Dante, R., Liu, P., Gronemeyer, H., Mendoza-Parra, M., Polo, J. M., Lavial, F.

Issue&Volume: 2022-09-08

Abstract: Coordinated changes of cellular plasticity and identity are critical for pluripotent reprogramming and oncogenic transformation. However, the sequences of events that orchestrate these intermingled modifications have never been comparatively dissected. Here, we deconvolute the cellular trajectories of reprogramming (via Oct4/Sox2/Klf4/c-Myc) and transformation (via Ras/c-Myc) at the single-cell resolution and reveal how the two processes intersect before they bifurcate. This approach led us to identify the transcription factor Bcl11b as a broad-range regulator of cell fate changes, as well as a pertinent marker to capture early cellular intermediates that emerge simultaneously during reprogramming and transformation. Multiomics characterization of these intermediates unveiled a c-Myc/Atoh8/Sfrp1 regulatory axis that constrains reprogramming, transformation and transdifferentiation. Mechanistically, we found that Atoh8 restrains cellular plasticity, independent of cellular identity, by binding a specific enhancer network. This study provides insights into the partitioned control of cellular plasticity and identity for both regenerative and cancer biology.

DOI: 10.1038/s41556-022-00986-w

Source: https://www.nature.com/articles/s41556-022-00986-w