Jia Nie, PhD

Research

Identify Molecular Mechanisms in Aged Mouse Pancreatic Islets

An estimated 33.9% of U.S. adults had prediabetes in 2015, and nearly half (48.3%) of adults aged 65 years or older had prediabetes.  Age is the main risk factor for the disease. The progressive deterioration of glucose tolerance from normal glucose tolerance (NGT) to impaired glucose tolerance, then to prediabetes and type 2 diabetes (T2D), will last several years. The acute insulin responses from pancreatic islet and insulin resistance are the primary determinants of glucose tolerance status over time. One of the hypotheses that links T2D with islet beta-cell mass is an initial proliferative expansion of beta-cell mass in the prediabetic state, followed by increased rates of beta-cell death after the onset of obesity. However, due to the limitations of postmortem studies performed after the onset of diabetes, the increased beta-cell mass required to maintain NGT in the early stages of T2D would not be detectable in humans and the molecular mechanism during this period remains unclear.

To better understand the cell heterogeneity within the aged islet, we applied single-cell RNA-Seq and single-cell western blot experiments in mouse islets of different ages and compared the transcriptional profile during aging. We further assessed the metabolic impact of long-term administration of a high-fat diet (HFD) to young and aged mice. We measure insulin secretion dynamics by the islet perifusion assay, use the microscopy method for cell morphology analysis, perform fluorescent staining for cell markers, and construct the in vivo mouse models for physiological and pathophysiological phenomena. We also further test our hypothesis in the common marmoset (Callithrix jacchus) by examining beta-cell dysfunction, glucose intolerance, and insulin sensitivity.

Single-Nucleus RNA Profiling of Human Adipose Tissues to Identify Cell Communication During Aging

White adipose tissue (WAT) is an extremely flexible organ with a remarkable ability to adapt to changes throughout the human lifespan. With aging and obesity, adipose tissue undergoes significant changes in abundance, distribution, cellular composition, and endocrine signaling. It plays a central role in developing insulin resistance, metabolic dysfunction, inflammation, and impaired regenerative capacity. Importantly, the subcutaneous and visceral adipose depots differ in their effects on metabolism. While visceral adipose tissue (VAT) is associated with pathological conditions, such as insulin resistance and cardiovascular diseases, subcutaneous adipose tissue (SAT) is protective against these diseases in humans. Loss of SAT is a common feature with advancing age in both mice and humans. Thus, a comprehensive insight into the cell composition changes in SAT during aging is critical for understanding the cellular and molecular mechanisms driving SAT plasticity and the associated comorbidities.

Here, we applied single-nucleus RNA-sequencing (snRNA-seq) to obtain cell-type-resolved insight into the transcriptional reprogramming and tissue remodeling of human SAT, samples across middle (40–65 years of age) to older (> 65 years of age) group. Using bioinformatics tools, we found new adipocyte subpopulations with distinct functions and constructed an in vivo adipogenesis trajectory in human SAT that covers a full transition path from adipocyte progenitors to mature adipocytes. We investigate the communication between different cell types by ex-vivo cell culture experiment and spatial transcriptomics method.

Awards & Accomplishments

Publications

Complete List of Published Works in My Bibliography:

https://www.ncbi.nlm.nih.gov/myncbi/jia.nie.1/bibliography/public/