Differentiation success of reprogrammed cells is heterogeneous in vivo and modulated by somatic cell identity memory.

IF 5.9 2区 医学 Q1 CELL & TISSUE ENGINEERING Stem Cell Reports Pub Date : 2025-03-12 DOI:10.1016/j.stemcr.2025.102447
Tomas Zikmund, Jonathan Fiorentino, Chris Penfold, Marco Stock, Polina Shpudeiko, Gaurav Agarwal, Larissa Langfeld, Kseniya Petrova, Leonid Peshkin, Stephan Hamperl, Antonio Scialdone, Eva Hoermanseder
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Abstract

Nuclear reprogramming can change cellular fates. Yet, reprogramming efficiency is low, and the resulting cell types are often not functional. Here, we used nuclear transfer to eggs to follow single cells during reprogramming in vivo. We show that the differentiation success of reprogrammed cells varies across cell types and depends on the expression of genes specific to the previous cellular identity. We find subsets of reprogramming-resistant cells that fail to form functional cell types, undergo cell death, or disrupt normal body patterning. Reducing expression levels of genes specific to the cell type of origin leads to better reprogramming and improved differentiation trajectories. Thus, our work demonstrates that failing to reprogram in vivo is cell type specific and emphasizes the necessity of minimizing aberrant transcripts of the previous somatic identity for improving reprogramming.

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核重编可以改变细胞的命运。然而,重编程的效率很低,产生的细胞类型往往不具备功能。在这里,我们利用核移植到卵子中来跟踪单个细胞在体内重编程的过程。我们发现,重编程细胞的分化成功率因细胞类型而异,并取决于先前细胞身份特异性基因的表达。我们发现了抗重编细胞亚群,它们无法形成功能细胞类型、发生细胞死亡或破坏正常的身体形态。降低原细胞类型特异性基因的表达水平,可以更好地进行重编程并改善分化轨迹。因此,我们的研究表明,体内重编程失败是细胞类型特异性的结果,并强调有必要尽量减少先前体细胞特征的异常转录本,以改善重编程。
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来源期刊
Stem Cell Reports
Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY
CiteScore
10.50
自引率
1.70%
发文量
200
审稿时长
28 weeks
期刊介绍: Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.
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