Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective To explore the doctor-nurse integrated health care management model in perioperative nursing management of transvaginal natural orifice transluminal endoscopic surgery (NOTES). Methods A total of 70 female patients underwent transvaginal NOTES. All patients were randomly divided into the control and the study groups. The control group adopted the traditional model of care, and the study group implemented a layered panel system of integrated health care nursing mode, which consisted of three lines (leader), second line, front-line doctors, anesthesiologists consisting of the doctor series and secondary responsibility leader, a responsibility of nurses, operating room nurses laparoscopy group traveling together constituted a series of nurses′ health care integration of the health care team. The average length of stay, preoperative waiting days, awareness of the disease, early postoperative activities and reasonable diet, patient satisfaction with care, doctors′ satisfaction with nurses′ operation and overall satisfaction with health care work were compared. Results The preoperative waiting days, average length of stay, surgical satisfaction, patients′ satisfaction, doctors-nurses′overall satisfaction in the study group were (3.95±0.51) d, (11.58±1.83) d, (95.48±3.82)%, (99.26± 0.61)%, (96.33±0.29)%, the control group were (5.50±0.68) d, (15.79±2.14) d, (82.08±7.21)%, (92.18± 3.54)%, (80.03 ± 5.88)%, the differences were statistically significant (t=-4.431-6.172, P < 0.05). The patients awareness of the disease, early postoperative activities and reasonable diet (postoperative eating time) in the study group were (92.77 ± 0.59)%, (1.60 ± 0.63) d, (2.20 ± 0.54) d, the control group were (93.15 ± 0.47)%, (1.90 ± 0.42) d, (2.40 ± 0.33) d, the difference was not statistically significant (t=-0.898,-0.771,-0.201, P>0.05). Conclusions The implementation ofdoctor-nurse integrated health carenew model can optimize the collocation of medical health care integration, enhance the quality of care, improve patient experience, and improve patients′and doctors′satisfaction for nursing work.