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<p>Stem-like progenitor CD8<sup>+</sup> T (T<sub>PRO</sub>) cells sustain cytotoxic immunity during chronic infection and cancer through quiescence, multipotency and self-renewal, hallmarks shared with memory T cells. However, how these properties are maintained under persistent antigen stimulation remains unclear. Here we identify the genomic organizer SATB1 as selectively enriched in both T<sub>PRO</sub> and memory CD8<sup>+</sup> T cells. Given its role in promoting quiescence in hematopoietic stem cells, we hypothesized that SATB1 supports CD8<sup>+</sup> T cell stemness. Using CD8<sup>+</sup> T cell-specific CRISPR deletion of the <i>Satb1</i> gene, we show that SATB1 is essential for maintaining T<sub>PRO</sub> cells during chronic lymphocytic choriomeningitis virus infection and for memory CD8<sup>+</sup> T cell formation during acute infection. Multi-omic profiling revealed that SATB1 regulates the chromatin accessibility, transcriptional activity and genome architecture of stemness-associated genes including <i>Tcf7</i>, <i>Bach2</i> and <i>Myb</i>. These findings reveal a critical role for SATB1 in preserving the transcriptional and epigenetic programs that sustain the stem-like state of antigen-specific CD8<sup>+</sup> T cells.</p>

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SATB1 is a key regulator of quiescence in stem-like CD8+ T cells

  • 期刊论文

  • 发表日期：

    2025年8月22日

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  • Siying Lin,
  • Hongshen Niu,
  • Yuqi Zhang,
  • Kexin Gai,
  • Ryan Brown,
  • Ashley Brown,
  • Jian Shen,
  • Ziyang Xu,
  • Ravi K. Shah,
  • Jessica L. Schmeling,
  • Marlenny Vargas-Cortes,
  • Anthony E. Zamora,
  • Terumi Kohwi-Shigematsu,
  • Jie Fan,
  • Bin Zhang,
  • Weiguo Cui

摘要

Stem-like progenitor CD8+ T (TPRO) cells sustain cytotoxic immunity during chronic infection and cancer through quiescence, multipotency and self-renewal, hallmarks shared with memory T cells. However, how these properties are maintained under persistent antigen stimulation remains unclear. Here we identify the genomic organizer SATB1 as selectively enriched in both TPRO and memory CD8+ T cells. Given its role in promoting quiescence in hematopoietic stem cells, we hypothesized that SATB1 supports CD8+ T cell stemness. Using CD8+ T cell-specific CRISPR deletion of the Satb1 gene, we show that SATB1 is essential for maintaining TPRO cells during chronic lymphocytic choriomeningitis virus infection and for memory CD8+ T cell formation during acute infection. Multi-omic profiling revealed that SATB1 regulates the chromatin accessibility, transcriptional activity and genome architecture of stemness-associated genes including Tcf7, Bach2 and Myb. These findings reveal a critical role for SATB1 in preserving the transcriptional and epigenetic programs that sustain the stem-like state of antigen-specific CD8+ T cells.