Gene expression profile of hiPSC-derived cells differentiated with growth factors, forskolin and conditioned medium from human adrenocortical cell line.

Abstract

Background: Adrenocortical carcinoma (ACC) affects approx. 2 in 1,000,000 individuals in the USA, and is more common in females than males. Adrenocortical carcinoma often presents with severe symptoms, such as abdominal pain, high blood pressure, acne, hair overgrowth, and voice deepening.

Objectives: Research on ACC constitutes a large body of published data. There is an increased need for easy access to ACC-derived biological material. Moreover, there are limited numbers of human cell lines available. For this reason, we attempted to differentiate human induced pluripotent stem cells (hiPSCs) into adrenocortical-like cells to establish a new functional cell line.

Material and methods: We conducted a long-term differentiation process (35 and 70 days) in the presence of growth factors (GFs), forskolin and conditioned medium collected from the human adrenal carcinoma (HAC15) cell line. Then, we analyzed the gene expression profile of the differentiated cells.

Results: The obtained cells possess features characteristic of all 3 primary germ layers. Interestingly, the differentiated cells demonstrated an extremely high level of gene expression for those involved in endocrine processes, namely glycoprotein hormones, alpha polypeptide (CGA), insulin receptor substrate 4 (IRS4), and pancreatic progenitor cell differentiation and proliferation factor-like protein (PPDPFL).

Conclusions: The results of the study indicate that we obtained progenitors derived from endoderm with some characteristics of pancreatic-like cells. The endodermal derivative differentiation is a very challenging and complicated process; thus, the results presented in this study deserve closer consideration.