Understand Biology Using Single Cell RNA-Sequencing

This dissertation summarizes the development of experimental and analytical tools for single cell RNA sequencing (scRNA-Seq), including 1) scPLATE-Seq, a FACS- and plate-based scRNASeq platform, which is accurate, robust, fully automated and cost-efficient; 2) metaVIPER, an algorithm for transcriptional regulator activity inference based on scRNA-Seq profiles; and 3) iterClust, a statistical framework for iterative clustering analysis, especially suitable for dissecting hierarchy of heterogeneity among single cells. Further this dissertation summarizes biological questions answered by combining these tools, including 1) understanding inter- and intra-tumor heterogeneity of human glioblastoma; 2) elucidating regulators of β-cell de-differentiation in type-2 diabetes; and 3) developing novel therapeutics targeting cell-state regulators of breast cancer stem cells

Bone Marrow Myeloid Cells Regulate Myeloid-Biased Hematopoietic Stem Cells via a Histamine-Dependent Feedback Loop

Myeloid-biased hematopoietic stem cells (MB-HSCs) play critical roles in recovery from injury, but little is known about how they are regulated within the bone marrow niche. Here we describe an auto-/paracrine physiologic circuit that controls quiescence of MB-HSCs and hematopoietic progenitors marked by histidine decarboxylase (Hdc). Committed Hdc+ myeloid cells lie in close anatomical proximity to MB-HSCs and produce histamine, which activates the H2 receptor on MB-HSCs to promote their quiescence and self-renewal. Depleting histamine-producing cells enforces cell cycle entry, induces loss of serial transplant capacity, and sensitizes animals to chemotherapeutic injury. Increasing demand for myeloid cells via lipopolysaccharide (LPS) treatment specifically recruits MB-HSCs and progenitors into the cell cycle; cycling MB-HSCs fail to revert into quiescence in the absence of histamine feedback, leading to their depletion, while an H2 agonist protects MB-HSCs from depletion after sepsis. Thus, histamine couples lineage-specific physiological demands to intrinsically primed MB-HSCs to enforce homeostasis. Chen et al. show that histidine decarboxylase (Hdc) marks quiescent myeloid-biased HSCs (MB-HSCs). Daughter myeloid cells form a spatial cluster with Hdc+ MB-HSCs and secrete histamine to enforce their quiescence and protect them from depletion, following activation by a variety of physiologic insults

Human GBM ARACNe Network

ARACNe gene regulatory networks for human glioblastoma

Human Melanoma Interactome Set (SKCM, T and B Lymphocyte)

Human melanoma interactome set, including SKCM, T and B Lymphocyte interactome

Simultaneous Determination of Three Effective Components in Different Compatibility Proportion of the Couple of Sophora flavescens-Fructus Ligustri lucidi by HPLC

Sophora flavescens - Ligustrum lucidum has the effect of increasing the anti-cancer effect of white blood cells and treating liver fibrosis. In order to determine the optimal compatibility ratio of this drug pair, the rationality of the drug pairs in different proportions was revealed. In this experiment, three active ingredients of the Sophora flavescens-Fructus Ligustri lucidi were extracted by reflux extraction, which were matrine, oxymatrine and specnuezhenide. A method for simultaneously determining the content of matrine, oxymatrine and specnuezhenide in a short time by HPLC was established. The method is simple, precise, and stable. Reproducibility can be used to determine the content of three active ingredients of matrine, oxymatrineand specnuezhenide. The analysis results was indicated that the different proportions of compatibility and different extraction solvents have significant effects on the content of active ingredients and dissolution rate of Sophora flavescens- Fructus Ligustri lucidi, after the combination of Sophora flavescens- Fructus Ligustri lucidi in different proportions, the content of matrine, oxymatrine and specnuezhenide is greater than the content of the active ingredients of each single herb. When the ratio of compatibility of Sophora flavescens-Ligustrum Ligustri lucidi is <1:1, it is beneficial to the dissolution of the three active ingredients. By determining the optimal compatibility ratio of this drug pair, provided a theoretical basis for the study of late pharmacodynamics and provide theoretical basis for clinicalapplication of traditional Chinese medicine

Simultaneous Determination of Three Effective Components in Different Compatibility Proportion of the Couple of Sophora flavescens-Fructus Ligustri lucidi by HPLC

Sophora flavescens - Ligustrum lucidum has the effect of increasing the anti-cancer effect of white blood cells and treating liver fibrosis. In order to determine the optimal compatibility ratio of this drug pair, the rationality of the drug pairs in different proportions was revealed. In this experiment, three active ingredients of the Sophora flavescens-Fructus Ligustri lucidi were extracted by reflux extraction, which were matrine, oxymatrine and specnuezhenide. A method for simultaneously determining the content of matrine, oxymatrine and specnuezhenide in a short time by HPLC was established. The method is simple, precise, and stable. Reproducibility can be used to determine the content of three active ingredients of matrine, oxymatrineand specnuezhenide. The analysis results was indicated that the different proportions of compatibility and different extraction solvents have significant effects on the content of active ingredients and dissolution rate of Sophora flavescens- Fructus Ligustri lucidi, after the combination of Sophora flavescens- Fructus Ligustri lucidi in different proportions, the content of matrine, oxymatrine and specnuezhenide is greater than the content of the active ingredients of each single herb. When the ratio of compatibility of Sophora flavescens-Ligustrum Ligustri lucidi is <1:1, it is beneficial to the dissolution of the three active ingredients. By determining the optimal compatibility ratio of this drug pair, provided a theoretical basis for the study of late pharmacodynamics and provide theoretical basis for clinicalapplication of traditional Chinese medicine

Efficiency of Sophora flavescens-Fructus Ligustri Lucidi Drug Pairs in the Treatment of Liver Fibrosis Based on the Response Surface Method

The pairing of Sophora flavescens and Fructus Ligustri lucidi is taken from Shi Jinmo Medicine. The idea behind this pairing was inspired by the similarity in pharmacological effects of the two herbal drugs, both of which are known to be effective in the treatment and protection against liver fibrosis. To quantitatively study the extent of the interaction between these drugs and the effect of pairing on the treatment of liver fibrosis, an animal model of liver fibrosis mice was established by intraperitoneal injection of low-dose carbon tetrachloride. The drugs were then administered individually, or in predefined compatibility ratio pairs, by gavage, and the effects on indexes of liver fibrosis were observed. The multisynthetic index method was adopted using Matlab software in order to construct a three-dimensional response surface map of the integration effect and conduct interaction analysis of Sophora flavescens and Fructus Ligustri lucidi. The quadratic surface fitting pattern was designed by quadratic regression to determine the optimal range of each drug. The obtained results show that when the compatibility ratio of Sophora flavescens-Fructus Ligustri lucidi drug pairs is less than or equal to 1:1, their therapeutic effect is enhanced by synergy (interaction value ranging between -0.2 and -1). Overall, the synergy of the high-dose drug pairs is stronger than that of the low-dose drug pairs. The optimal dose ranges are 6~12 g and 8~17 g for Sophora flavescens and Fructus Ligustri lucidi, respectively