Biology subjects

Lee, T.-L.

Publications and source records attributed to Lee, T.-L..

4 recordsLinked to original sources

bioRxiv2023

MiR-221/222-enriched ADSC-exosome mitigates PM exposure-exacerbated cardiac ischemia/reperfusion injury through the modulation of the BNIP3/LC3B/PUMA pathway

BackgroundEpidemiology has demonstrated a strong relationship between fine particulate matter (PM) exposure and cardiovascular disease. Whether PM aggravates myocardial ischemia/reperfusion (I/R) injury and its related mechanisms remain unclear. Our previous study showed that adipose stem cell-derived exosomes (ADSC-Exo) contain a large amount of miR-221/222. This study investigated the effects of PM exposure on I/R-induced cardiac injury through mitophagy and apoptosis, as well as the potential role of miR-221/222 in ADSC-Exo. MethodsWild-type, miR-221/222 knockout (miR-221/222 KO), and miR-221/222 overexpressed transgenic (miR-221/222 TG) mice were intratracheally injected with 100 g/kg PM for 24 h before I/R treatment. Ischemia was induced by temporarily occluding the left anterior descending (LAD) coronary artery with sutures for 30 min, followed by 3 h of reperfusion. In an in vitro model, H9c2 cells were exposed to 50 g/mL PM for 6 h and subjected to hypoxia (1% O2) at 37{degrees}C for 6 h, followed by 12 h reoxygenation. ResultsPM aggravates I/R (H/R)-induced cardiac injury by increasing ROS levels and causing mitochondrial dysfunction, leading to an increase in mitochondrial fission-related proteins like Drp1 and Mff, mitophagy-related proteins such as BNIP3 and LC3B, as well as apoptosis-related proteins like PUMA and p-p53 in vivo and in vitro studies. In comparison, transfection of ADSC-Exo and miR-221/222 mimics significantly reduced PM+I/R (H/R)-induced cardiac injury. Importantly, ADSC-Exo contains miR-221/222, which directly targets BNIP3, LC3B, and PUMA, decreasing their expression and ultimately reducing cardiomyocyte mitophagy and apoptosis. ConclusionsThe study showed that PM aggravates I/R or H/R-induced cardiac injury, and ADSC-Exo treatment significantly reduced this by regulating mitophagy and apoptosis through miR-221/222/BNIP3/LC3B/PUMA.

cell biology↗

bioRxiv2023

Hematopoietic Transfer of the Anti-Cancer and Lifespan-Extending Capabilities of A Genetically Engineered Blood System

A causal relationship exists among the aging process, organ decay and dis-function, and the occurrence of various diseases including cancer. A genetically engineered mouse model, termed Klf1K74R/K74R or Klf1(K74R), carrying mutation on the well-conserved sumoylation site of the hematopoietic transcription factor KLF1/ EKLF has been generated that possesses extended lifespan and healthy characteristics including cancer resistance. We show that the healthy longevity characteristics of the Klf1(K74R) mice, as exemplified by their higher anti- cancer capability, are likely gender-, age- and genetic background-independent. Significantly, the anti-cancer capability, in particular that against melanoma as well as hepatocellular carcinoma, and lifespan-extending property of Klf1(K74R) mice could be transferred to wild-type mice via transplantation of their bone marrow mononuclear cells at young age of the latter. Furthermore, NK(K74R) cells carry higher in vitro cancer cell-killing ability than wild type NK cells. Targeted/global gene expression profiling analysis has identified changes of the expression of specific proteins, including the immune checkpoint factors PDCD and CD274, and cellular pathways in the leukocytes of the Klf1(K74R) that are in the directions of anti-cancer and/or anti-aging. This study demonstrates the feasibility of developing a transferable hematopoietic/ blood system for long-term anti-cancer and, potentially, for anti-aging.

cancer biology↗

bioRxiv2021

A Positive Regulatory Feedback Loop Between 1 EKLF/ KLF1 and TAL1/SCL2 Sustaining the Erythropoiesis

The erythroid Kruppel-like factor EKLF/KLF1 is a hematopoietic transcription factor binding to CACCC DNA motif and participating in the regulation of erythroid differentiation. With combined use of microarray-based gene expression profiling and promoter-based ChIP-chip assay of E14.5 fetal liver cells from wild type (WT) and EKLF-knockout (Eklf-/-) mouse embryos, we have identified the pathways and direct target genes activated or repressed by EKLF. This genome-wide study together with molecular/cellular analysis of mouse erythroleukemic cells (MEL) indicate that among the downstream direct target genes of EKLF is Tal1/Scl. Tal1/Scl encodes another DNA-binding hematopoietic transcription factor TAL1/SCL known to be an Eklf activator and essential for definitive erythroid differentiation. Further identification of the authentic Tall gene promoter in combination with in vivo genomic footprinting approach and DNA reporter assay demonstrate that EKLF activates Tall gene through binding to a specific CACCC motif located in its promoter. These data establish the existence of a previously unknow positive regulatory feedback loop between two DNA-binding hematopoietic transcription factors that sustains the mammalian erythropoiesis.

cell biology↗

bioRxiv2017

Single-cell RNA-Seq Resolves Cellular Heterogeneity and Transcriptional Dynamics during Spermatogonia Stem Cells Establishment and Differentiation

The transition of gonocytes to spermatogonia and subsequent differentiation provide the foundation of spermatogenesis. However, systematic understanding on the cellular and molecular basis of this process is still limited, mainly impeded by the asynchrony in development and the lack of stage-specific markers. Using single-cell RNA sequencing on Oct4-GFP+/KIT- cells isolated from PND5.5 mice, we dissected the cellular heterogeneity and established molecular regulations. We demonstrated that gonocyte-spermatogonial transition was characterized by gene expression change related to apoptosis, cell cycle progression, and regulation of migration processes. Pseudotime analysis reconstructed developmental dynamics of the spermatogonial populations and unraveled sequential cellular and molecular transitions. We also identified CD87 as a neonatal stem cell marker which are potentially involved in the intial establishment of SSC pool. Lastly, we uncovered an unexpected subpopulation of spermatogonia primed to differentiation within the undifferentiated compartment, which is characterized by the lack of self-renewal genes and enhanced Oct4 expression and retinoic acid signaling response. Our study thus provides a novel understanding of cellular and molecular changes during spermatogonial establishment.

developmental biology↗