Division of Cardiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA.
Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA.
Stem Cells. 2022 Oct 21;40(10):932-948. doi: 10.1093/stmcls/sxac048.
Adipose-derived cells (ADCs) from white adipose tissue are promising stem cell candidates because of their large regenerative reserves and the potential for cardiac regeneration. However, given the heterogeneity of ADC and its unsolved mechanisms of cardiac acquisition, ADC-cardiac transition efficiency remains low. In this study, we explored the heterogeneity of ADCs and the cellular kinetics of 39,432 single-cell transcriptomes along the leukemia inhibitory factor (LIF)-induced ADC-cardiac transition. We identified distinct ADC subpopulations that reacted differentially to LIF when entering the cardiomyogenic program, further demonstrating that ADC-myogenesis is time-dependent and initiates from transient changes in nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. At later stages, pseudotime analysis of ADCs navigated a trajectory with 2 branches corresponding to activated myofibroblast or cardiomyocyte-like cells. Our findings offer a high-resolution dissection of ADC heterogeneity and cell fate during ADC-cardiac transition, thus providing new insights into potential cardiac stem cells.
脂肪组织来源的细胞（ADCs）因其具有较大的再生储备能力和潜在的心脏再生能力，是有前途的干细胞候选者。然而，鉴于 ADC 的异质性及其心脏获得的未解决机制，ADC 向心脏的转化效率仍然较低。在这项研究中，我们探讨了 ADC 的异质性以及沿着白血病抑制因子（LIF）诱导的 ADC 向心脏转化过程中 39432 个单细胞转录组的细胞动力学。我们鉴定了不同的 ADC 亚群，当它们进入心肌生成程序时，对 LIF 的反应不同，这进一步表明 ADC 肌生成是时间依赖性的，并且是由核因子红细胞 2 相关因子 2（Nrf2）信号的短暂变化引发的。在后期，ADC 的拟时间分析导航了一个具有 2 个分支的轨迹，对应于激活的成肌纤维细胞或类似于心肌细胞的细胞。我们的研究结果提供了 ADC 异质性和 ADC 向心脏转化过程中细胞命运的高分辨率剖析，从而为潜在的心脏干细胞提供了新的见解。
