Scholarlink

<p>Differentiation of induced pluripotent stem cells (iPSCs) into specialized cell types is essential for uncovering cell-type specific molecular mechanisms and interrogating cellular function. Transcription factor screens have enabled efficient production of a few cell types; however, engineering cell types that require complex transcription factor combinations remains challenging. Here, we report an iterative, high-throughput single-cell transcription factor screening method that enables the identification of transcription factor combinations for specialized cell differentiation, which we validated by differentiating human microglia-like cells. We found that the expression of six transcription factors, SPI1, CEBPA, FLI1, MEF2C, CEBPB, and IRF8, is sufficient to differentiate human iPSC into cells with transcriptional and functional similarity to primary human microglia within 4 days. Through this screening method, we also describe a novel computational method allowing the exploration of single-cell RNA sequencing data derived from transcription factor perturbation assays to construct causal gene regulatory networks for future cell fate engineering.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Iterative transcription factor screening enables rapid generation of microglia-like cells from human iPSC

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月10日

查看全文
  • Songlei Liu,
  • Li Li,
  • Fan Zhang,
  • Mariana Garcia-Corral,
  • Katharina Meyer,
  • Patrick R. J. Fortuna,
  • Björn van Sambeek,
  • Evan Appleton,
  • Alex H. M. Ng,
  • Parastoo Khoshakhlagh,
  • Yuancheng Ryan Lu,
  • James Cameron,
  • Ricardo N. Ramirez,
  • Yuting Chen,
  • Chun-Ting Wu,
  • Jeremy Y. Huang,
  • Yuqi Tan,
  • George Chao,
  • John Aach,
  • Elaine T. Lim,
  • Jenny M. Tam,
  • Soumya Raychaudhuri,
  • George M. Church

摘要

Differentiation of induced pluripotent stem cells (iPSCs) into specialized cell types is essential for uncovering cell-type specific molecular mechanisms and interrogating cellular function. Transcription factor screens have enabled efficient production of a few cell types; however, engineering cell types that require complex transcription factor combinations remains challenging. Here, we report an iterative, high-throughput single-cell transcription factor screening method that enables the identification of transcription factor combinations for specialized cell differentiation, which we validated by differentiating human microglia-like cells. We found that the expression of six transcription factors, SPI1, CEBPA, FLI1, MEF2C, CEBPB, and IRF8, is sufficient to differentiate human iPSC into cells with transcriptional and functional similarity to primary human microglia within 4 days. Through this screening method, we also describe a novel computational method allowing the exploration of single-cell RNA sequencing data derived from transcription factor perturbation assays to construct causal gene regulatory networks for future cell fate engineering.