Zhen Liu

All Publications

• Epigenetic imprinting in innate lymphoid cell precursors directs the lineage segregation of innate lymphoid cells. Nature immunology Liu, Z., Shao, F., Zhang, Q., Zhao, M., Gao, S., Zhang, X., Yu, D., Zhang, J., Xia, P., Wang, S. 2025; 26 (10): 1686-1698

  Abstract

  Innate lymphoid cells (ILCs) are essential for mucosal homeostasis, but the epigenetic regulation of their lineage segregation remains elusive. Here we simultaneously profiled the single-cell DNA methylome, chromatin accessibility and transcriptome of ILC subsets and ILC precursors (ILCPs) and found that ILCPs could be divided into two subgroups (ILCP1 and ILCP2). ILCP2s had highly heterogeneous DNA methylation profiles and could be divided into three groups according to their DNA methylation characteristics, which matched those of ILC subsets. We identified the signature methylation regions (SMRs) of each ILC subset and traced the DNA methylation imprinting during ILCP differentiation. ILCP2s with hypomethylated SMRs characteristic of ILC subsets differentiated into those subsets. DNA methylation editing of SMRs suppressed ILC lineage segregation, while deletion of Dnmt1 in ILCPs abrogated the heterogeneous distribution of SMRs and resulted in ILC differentiation defects. These findings provide evidence that epigenetic imprinting determines lineage segregation during immune cell development.

  View details for DOI 10.1038/s41590-025-02261-0

  View details for PubMedID 40968162

  View details for PubMedCentralID 4003507

• FOXO1 orchestrates the intestinal homeostasis via neuronal signaling in group 3 innate lymphoid cells. The Journal of experimental medicine Shao, F., Liu, Z., Wei, Q., Yu, D., Zhao, M., Zhang, X., Gao, X., Fan, Z., Wang, S. 2023; 220 (10)

  Abstract

  The neuro-immune regulation is associated with homeostasis of the intestine. Intestinal group 3 innate lymphoid cells (ILC3s) are tissue-resident lymphocytes whose functions are affected by the intestine niche. However, how a gut neuronal signal coordinates the immune response of ILC3s is largely unknown. Here, we found that cyclic adenosine monophosphate (cAMP) signaling exacerbated the inflammatory response and attenuated the expression level of the transcription factor forkhead box O1 (FOXO1) in ILC3s. Deficiency of FOXO1 drove the hyperactivation of ILC3s and resulted in gut inflammation independently of T cells. Mechanistically, FOXO1 promoted the transcription of neuropeptide receptor VIPR2 and inhibited the transcription of adrenoceptor ADRA2A in ILC3s. FOXO1-related regulation of VIPR2 and ADRA2A signaling balanced the activation of ILC3s under steady condition or during colitis. Moreover, chronic stress elevated cAMP level and downregulated FOXO1 level, exacerbating intestinal inflammation. Our findings reveal that FOXO1 balances the activation of ILC3s via VIP and adrenergic signaling and regulates intestinal homeostasis.

  View details for DOI 10.1084/jem.20230133

  View details for PubMedID 37549024

  View details for PubMedCentralID PMC10405431

• A “Cool” route to the Higgs boson and beyond. The Cool Copper Collider JINST - Journal of Instrumentation Vernieri, C., Nanni, E., Dasu, S., Peskin, M., Ntounis, D., et al 2023; 18 (07)

  View details for DOI 10.1088/1748-0221/18/07/P07053