Single-cell RNA-seq Identifies Dynamic Cardiac Transition Program from Adipose Derived Cells Induced by Leukemia Inhibitory Factor
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ABSTRACT: Adipose-derived cells (ADCs) from white adipose tissue (WAT) are promising stem cell candidates due to large innate regenerative reserves and achievement of clinically meaningful cardiac regeneration. However, due to the heterogeneity of ADCs and unsolved molecular mechanism underpins of cardiac acquisition, the ADC-Cardiac transition efficiency remains low. Here, we found a population of ADCs reacted to leukemia inhibitory factor (LIF) and differentiated into functional beating cardiomyocyte-like cells. With single cells sequencing, we profiled 39,432 single cell transcriptomes at multiple time points throught the cardiac transition course. Combined with FACS, we identified three distinct pdgfra+ ADC populations that responded differently to the LIF signaling and transited to cardiomyocyte like cells. Dynamic trajectories derived from pseudotime analysis on ADCs navigate a trajectory with two branches that correspond to two alternative fate decisions. Analysis of starting branch revealed Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling is the crucial event in initiation of myogenic program. The ending two branches represented activated myofibroblast and cardiomyocyte like cells. Collectively, our findings offer a high-resolution dissection of ADC heterogeneity and cell fate dynamics during ADCs-Cardiac transition, thus shed new insights into potential cardiac stem cells for future usage.
ORGANISM(S): Mus musculus
PROVIDER: GSE164410 | GEO | 2022/10/26
REPOSITORIES: GEO
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