BACH2 enforces the transcriptional and epigenetic programs of stem-like CD8+ T cells

Chen Yao, Guohua Lou, Hong Wei Sun, Ziang Zhu, Yi Sun, Zeyu Chen, Daniel Chauss, E. Ashley Moseman, Jun Cheng, Marc A. D’Antonio, Wangke Shi, Junwei Shi, Kohei Kometani, Tomohiro Kurosaki, E. John Wherry, Behdad Afzali, Luca Gattinoni, Yuwen Zhu, Dorian B. McGavern, John J. O’SheaPamela L. Schwartzberg, Tuoqi Wu

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


During chronic infection and cancer, a self-renewing CD8+ T cell subset maintains long-term immunity and is critical to the effectiveness of immunotherapy. These stem-like CD8+ T cells diverge from other CD8+ subsets early after chronic viral infection. However, pathways guarding stem-like CD8+ T cells against terminal exhaustion remain unclear. Here, we show that the gene encoding transcriptional repressor BACH2 is transcriptionally and epigenetically active in stem-like CD8+ T cells but not terminally exhausted cells early after infection. BACH2 overexpression enforced stem-like cell fate, whereas BACH2 deficiency impaired stem-like CD8+ T cell differentiation. Single-cell transcriptomic and epigenomic approaches revealed that BACH2 established the transcriptional and epigenetic programs of stem-like CD8+ T cells. In addition, BACH2 suppressed the molecular program driving terminal exhaustion through transcriptional repression and epigenetic silencing. Thus, our study reveals a new pathway that enforces commitment to stem-like CD8+ lineage and prevents an alternative terminally exhausted cell fate.

Original languageEnglish (US)
Pages (from-to)370-380
Number of pages11
JournalNature immunology
Issue number3
StatePublished - Mar 2021
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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