Ying Liang

University of Kentucky | UKY · College of Medicine

In recent years, pharmacological ascorbic acid has emerged as a promising therapeutic approach in cancer treatment, owing to its capacity to induce extracellular hydrogen peroxide (H 2 O 2 ) production in solid tumors....

In recent years, small non-coding RNAs (ncRNAs) have emerged as a new player in the realm of cancer therapeutics. Their unique capacity to directly modulate genetic networks and target oncogenes positions them as valuable complements to existing small-molecule drugs. Concurrently, the advancement of small ncRNA-based therapeutics has rekindled the...

Iron oxide nanoparticles (IONPs) have garnered significant attention as a promising platform for reactive oxygen species (ROS)‐dependent disease treatment, owing to their remarkable biocompatibility and Fenton catalytic activity. However, the low catalytic activity of IONPs is a major hurdle in their clinical translation. To overcome this challenge...

Hematopoietic stem cells (HSCs) have the ability to self-renew and differentiate to all blood cell types. HSCs and their differentiated progeny show sex/gender differences. The fundamental mechanisms remain largely unexplored. We previously reported that latexin (Lxn) deletion increased HSC survival and repopulation capacity in female mice. Here, w...

Introduction Hematopoiesis is a continuous and well-regulated process requiring both the capacity for self-renewal and the potential for differentiation of hematopoietic stem cells. Results Multiple studies indicate that sex hormones exert significant effects on not only hematopoietic stem and progenitor cells, but also the development of hematopo...

Acute myeloid leukemia (AML) is the most commonly diagnosed adult leukemia. The MLL–AF9 fusion oncogenic protein is predominantly associated with leukemic stem cells (LSCs) transformation and expansion. AML disease initiation and progression are heavily influenced by the bone marrow (BM) microenvironment (or niche). Current treatment by targeting M...

Shwachman–Diamond syndrome (SDS) is a bone marrow failure (BMF) syndrome associated with an increased risk of myelodysplasia and leukemia. The molecular mechanisms of SDS are not fully understood. We report that primitive hematopoietic cells from SDS patients present with a reduced activity of the small RhoGTPase Cdc42 and concomitantly a reduced f...

Hematopoietic stem cells (HSCs) are ultimately responsible for the lifelong renewal of all blood cell lineages. In the bone marrow (BM), HSCs reside in specialized microenvironments referred to as the “niche.” HSC niche consists of complex components including heterogeneous cell populations, growth factors, and extracellular matrix molecules. The c...

Senescent cells (SnCs) accumulate with age. Genetic or pharmacological clearance of SnCs delays several age-associated disorders and extends the healthspan of both progeroid and wild-type (WT) mice (Baker DJ et al. Nature, 479: 232, 2011; Baker DJ et al. Nature, 530: 184, 2016). In addition, our previous study showed that transient depletion of SnC...

Hematopoietic stem cells provide life-long production of blood cells and undergo self-renewal division in order to sustain the stem cell pool. Homeostatic maintenance of HSC pool and blood cell production is vital for organismal survival. We previously reported that latexin is a negative regulator of HSCs in mice, whose natural variation in the exp...

Myelodysplastic syndromes (MDS) are a diverse group of malignant clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, dysplastic cell morphology in one or more hematopoietic lineages, and a risk of progression to acute myeloid leukemia (AML). Approximately 50% of MDS patients respond to current FDA-approved drug ther...

Natural genetic diversity offers an important yet largely untapped resource to decipher the molecular mechanisms regulating hematopoietic stem cell (HSC) function. Latexin (Lxn) is a negative stem cell regulatory gene identified on the basis of genetic diversity. By using an Lxn knockout mouse model, we found that Lxn inactivation in vivo led to th...

Supplementary material:Supplement 1. MnP treatment does not affect mature bone marrow cells by serial bone marrow transplantations. A. Donor cells were isolated from 60-day vehicle or MnP in vivo- treated mice. B. The donor cells were in vitro treated with vehicle or 20 μM MnP (MnP) for 16 h. Percentage of donor derived Granulocyte, T-cell, B-cell...

The signaling of reactive oxygen species (ROS) is essential for the maintenance of normal cellular function. However, whether and how ROS regulate stem cells are unclear. Here, we demonstrate that, in transgenic mice expressing the human manganese superoxide dismutase (MnSOD) gene, a scavenger of ROS in mitochondria, the number and function of mous...

The large size of the pig and its similarity in anatomy, physiology, metabolism, and genetics to humans make it an ideal platform to develop a genetically defined, large animal model of cancer. To this end, we created a transgenic "oncopig" line encoding Cre recombinase inducible porcine transgenes encoding KRASG12D and TP53R167H, which represent a...

In order to take full advantage of the potential for new therapeutics and biotechnology applications, there is an urgent need for new animal models supporting cancer research. Pigs share many genetic and physiological similarities with humans. Our previous studies have shown that overexpression of several human oncogenes led to tumor development in...

Leukemia is a leading cause of cancer death. Recently, the latexin (Lxn) gene was identified as a potential tumor suppressor in several types of solid tumors and lymphoma, and Lxn expression was found to be absent or downregulated in leukemic cells. Whether Lxn functions as a tumor suppressor in leukemia and what molecular and cellular mechanisms a...

Common rodent-based models have limitations in terms of modeling human cancers. Given that pigs share many genetic and physiological similarities with humans, we investigated the potential of developing genetic porcine models of cancer. In this regard, we previously reported that activation of oncogenes like Ras in conjunction with inhibiting tumor...

2314 We have previously shown a novel role for Latexin (Lxn), a carboxypeptidase inhibitor, in influencing the size of murine hematopoietic stem cell (HSC) population. Lxn negatively regulates HSC population size by enhancing apoptosis while repressing proliferation and self-renewal. However, the major mechanisms underlying this phenotype remain un...

Latexin is a negative regulator of hematopoietic stem cell number in mice. Its dysregulated expression in other tumors led us to hypothesize that latexin may have tumor suppressor properties in hematological malignancies. We found that latexin was down-regulated in a variety of leukemia and lymphoma cell lines as well as in CD34+ cells from the blo...

Cpa3 is not expressed in A20 cells. Real-time PCR was performed on A20 cells that were either uninfected (A20 control) or infected with empty (vector control) or Lxn expression vector (Lxn vector) to quantify Cpa3 mRNA expression. The amplification plots for Lxn (A), Cpa3 (B) and Gapdh (C) transcript show that Lxn is highly expressed in A20 cells i...

Carboxypeptidase A3 (Cpa3) is highly expressed in stem/progenitor cells. Expression level of CPAs were measured by microarray on a bone marrow population null for cell markers characteristic of lineage-specific differentiated blood cells (Lin-negative), and positive for the Sca-1 and c-Kit cell markers (LSK) cells, enriched for hematopoietic stem/p...

Self-renewal and multilineage differentiation of stem cells are keys to the lifelong homeostatic maintenance of tissues and organs. Hematopoietic aging, characterized by immunosenescence, proinflammation, and anemia, is attributed to age-associated changes in the number and function of hematopoietic stem cells (HSCs) and their microenvironmental ni...

The B6.SJL-Ptprc(d)Pep3(b)/BoyJ (B6.SJL) congenic mouse strain, a valuable and widely used tool in murine bone marrow transplantation studies, has long been considered equivalent to the parental C57B/L6 (B6) strain with the exception of a small congenic interval on chromosome 1 harboring an alternative CD45/Ly-5 alloantigen (Ly-5.1). In this study...

Natural genetic diversity is a largely untapped reservoir for use in the discovery of stem cell regulatory pathways. Here we explore the means by which phenotypic diversity in mice can lead to the discovery of novel genes affecting stem cell regulation. We use as an example the discovery that latexin is a regulator of the natural size of the hemato...

A complex interaction of cell-intrinsic and extra-cellular signals cooperate to determine the number and behavior of Hematopoietic Stem Cells (HSCs). Elucidation of these regulatory networks promises to offer novel insights into HSC biology and HSC-mediated clinical therapies. In an effort to identify cell-intrinsic, genetic regulatory mechanisms d...

We recently found that latexin is a negative regulator of the size of the hematopoietic stem cell population in mice. It acts by increasing apoptosis and decreasing cell proliferation. This 29 kD protein bears a strong structural resemblance to tazarotene-induced gene 1 (TIG1), a tumor suppressor down-regulated in a variety of cancers. The structur...

There are many definitions of the term “ageing” and perhaps even more theories that seek to explain its causes (Balcombe and Sinclair 2001). From a physiological standpoint, ageing beyond reproductive maturity is often viewed as a progression of multisystem deficits in tissue function. In adult mammals, tissue homeostasis is maintained by stem cell...

Aging in a statistical sense is the increasing probability of death with increasing time of an organism’s existence (1, 2). Can we extrapolate this to self-regenerating tissues and most particularly to the stem cells that drive the replenishment of lost and damaged cells throughout life? To be succinct, how close is the linkage between the vitality...

We mapped quantitative trait loci that accounted for the variation in hematopoietic stem cell (HSC) numbers between young adult C57BL/6 (B6) and DBA/2 (D2) mice. In reciprocal chromosome 3 congenic mice, introgressed D2 alleles increased HSC numbers owing to enhanced proliferation and self-renewal and reduced apoptosis, whereas B6 alleles had the o...

Hematopoietic stem cell replacement therapy is an area of research lacking an optimal culture system that allows for the ex vivo expansion of CD34+ cells for transplant. The necessity for expansion is due to the lack of sufficient material from umbilical cord blood (UCB), the preferred source of CD34+ cells. The final composition of the expanded ce...

To investigate aging mechanisms in murine hematopoietic stem cells (HSCs), a microarray analysis was performed on sorted Lin-cKit+ Sca-1+ cells of young and old mice of two strains: long-lived C57B6L/6 (B6) and short-lived DBA/2 (D2). Following analysis by two-way ANOVA with a FDR of 5%, the data was organized using gene ontology software. The foll...

To test the hypothesis that aging has negative effects on stem-cell homing and engraftment, young or old C57BL/6 bone marrow (BM) cells were injected, using a limiting-dilution, competitive transplantation method, into old or young Ly5 congenic mice. Numbers of hematopoietic stem cells (HSCs) and progenitor cells (HPCs) recovered from BM or spleen...

The efficiency with which hematopoietic stem (HSC) and progenitor cells (HPC) home to bone marrow (BM) critically impacts their engraftment after transplantation. Little is known about the effects of aging on this parameter. The present study was thus initiated to test the hypothesis that homing efficiency of HSCs and HPCs to the BM will vary with...

The objectives of this review were first to critically review what is known about the effects of aging on stem cells in general, and hematopoietic stem cells in particular. Secondly, evidence is marshalled in support of the hypothesis that aging stem cells play a critical role in determining the effects of aging on organ function, and ultimately on...

Studies to uncover genes regulating stem cells usually adopt one of two distinct lines of investigation: forward genetics and reverse genetics approaches. The forward genetics approach proceeds from measurable phenotypic differences to genetic polymorphism and, as the name implies, the path of investigation is reversed using reverse genetics. The n...