Calico Life Sciences, LLC, 1170 Veterans Blvd, South San Francisco, CA 94080, USA.
Calico Life Sciences, LLC, 1170 Veterans Blvd, South San Francisco, CA 94080, USA.
Cell Syst. 2022 Jul 20;13(7):574-587.e11. doi: 10.1016/j.cels.2022.05.002. Epub 2022 Jun 10.
Partial pluripotent reprogramming can reverse features of aging in mammalian cells, but the impact on somatic identity and the necessity of individual reprogramming factors remain unknown. Here, we used single-cell genomics to map the identity trajectory induced by partial reprogramming in multiple murine cell types and dissected the influence of each factor by screening all Yamanaka Factor subsets with pooled single-cell screens. We found that partial reprogramming restored youthful expression in adipogenic and mesenchymal stem cells but also temporarily suppressed somatic identity programs. Our pooled screens revealed that many subsets of the Yamanaka Factors both restore youthful expression and suppress somatic identity, but these effects were not tightly entangled. We also found that a multipotent reprogramming strategy inspired by amphibian regeneration restored youthful expression in myogenic cells. Our results suggest that various sets of reprogramming factors can restore youthful expression with varying degrees of somatic identity suppression. A record of this paper's Transparent Peer Review process is included in the supplemental information.
部分多能性重编程可以逆转哺乳动物细胞衰老的特征，但对体细胞身份的影响以及单个重编程因子的必要性仍不清楚。在这里，我们使用单细胞基因组学来绘制多种鼠类细胞类型中部分重编程诱导的身份轨迹，并通过 pooled single-cell screens 筛选所有 Yamanaka 因子亚群来剖析每个因子的影响。我们发现，部分重编程在脂肪细胞和成纤维干细胞中恢复了年轻的表达，但也暂时抑制了体细胞身份程序。我们的 pooled screens 揭示了 Yamanaka 因子的许多亚群都可以恢复年轻的表达并抑制体细胞身份，但这些效果并没有紧密交织。我们还发现，受两栖动物再生启发的多能性重编程策略可以恢复肌源性细胞的年轻表达。我们的结果表明，各种重编程因子集可以在不同程度的体细胞身份抑制下恢复年轻的表达。本论文的透明同行评审过程记录包含在补充信息中。
