دورية أكاديمية

Decoding single-cell molecular mechanisms in astrocyte-to-iN reprogramming via Ngn2- and Pax6-mediated direct lineage switching

التفاصيل البيبلوغرافية
العنوان: Decoding single-cell molecular mechanisms in astrocyte-to-iN reprogramming via Ngn2- and Pax6-mediated direct lineage switching
المؤلفون: Rongxing Qin, Yingdan Zhang, Yue Yang, Jiafeng Chen, Lijuan Huang, Wei Xu, Qingchun Qin, Xiaojun Liang, Xinyu Lai, Xiaoying Huang, Minshan Xie, Li Chen
المصدر: European Journal of Medical Research, Vol 29, Iss 1, Pp 1-15 (2024)
بيانات النشر: BMC, 2024.
سنة النشر: 2024
المجموعة: LCC:Medicine
مصطلحات موضوعية: Medicine
الوصف: Abstract Background The limited regenerative capacity of damaged neurons in adult mammals severely restricts neural repair. Although stem cell transplantation is promising, its clinical application remains challenging. Direct reprogramming, which utilizes cell plasticity to regenerate neurons, is an emerging alternative approach. Methods We utilized primary postnatal cortical astrocytes for reprogramming induced neurons (iNs) through the viral-mediated overexpression of the transcription factors Ngn2 and Pax6 (NP). Fluorescence-activated cell sorting (FACS) was used to enrich successfully transfected cells, followed by single-cell RNA sequencing (scRNA-seq) using the 10 × Genomics platform for comprehensive transcriptomic analysis. Results The scRNA-seq revealed that NP overexpression led to the differentiation of astrocytes into iNs, with percentages of 36% and 39.3% on days 4 and 7 posttransduction, respectively. CytoTRACE predicted the developmental sequence, identifying astrocytes as the reprogramming starting point. Trajectory analysis depicted the dynamic changes in gene expression during the astrocyte-to-iN transition. Conclusions This study elucidates the molecular dynamics underlying astrocyte reprogramming into iNs, revealing key genes and pathways involved in this process. Our research contributes novel insights into the molecular mechanisms of NP-mediated reprogramming, suggesting avenues for optimizing the efficiency of the reprogramming process.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2047-783X
75895560
Relation: https://doaj.org/toc/2047-783X
DOI: 10.1186/s40001-024-01989-z
URL الوصول: https://doaj.org/article/a71bba5879ab4c758955609b0eacebb7
رقم الأكسشن: edsdoj.71bba5879ab4c758955609b0eacebb7
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2047783X
75895560
DOI:10.1186/s40001-024-01989-z