University of Arizona
Browse

Development of human pituitary adenoma organoids to facilitate effective targeted treatments of Cushing's disease

dataset
posted on 2022-07-06, 15:30 authored by Jayati ChakrabartiJayati Chakrabarti, Ritu Pandey, Jared Churko, Jennifer Eschbacher, Saptarshi Mallick, Yuliang Chen, Beth Hermes, Palash Mallick, Ben Stansfield, Kelvin W. Pond, Curtis Thorne, Kevin Yuen, Andrew S. Little, Yana Zavros

Cushing's disease (CD) is a serious endocrine disorder caused by an unregulated adrenocorticotropic hormone (ACTH)-secreting pituitary tumor that stimulates the adrenal glands to overproduce cortisol. Chronic exposure to excess cortisol has detrimental effects on health, including increased stroke rates, diabetes, obesity, cognitive impairment, anxiety, depression, and death. The first-line treatment for CD is pituitary surgery, which is followed by disease remission in only 47% of patients. The lack of specificity of current standard of care treatments with low efficacy and tolerability makes CD a medical therapeutic challenge. One major limitation that hinders the development of specific medical therapies is the lack of human relevant model systems that recapitulate the cellular composition of pituitary adenomas. Human pituitary adenoma tissue was harvested during transsphenoidal surgery from CD patients to generate organoids (hPITOs). hPITOs generated from corticotroph, lactotroph, gonadotroph and somatotroph adenomas exhibited morphological diversity among the organoid lines between individual patients and amongst subtypes. The similarity in cell lineages between the organoid line and the patient’s tumor was validated by comparing the neuropathology report, to the expression pattern of pituitary adenoma specific markers using spectral flow cytometry and exome sequencing. A high-throughput drug screen demonstrated patient-specific drug responses of hPITOs amongst each adenoma subtype. Generation of induced pluripotent stem cells (iPSCs) from patients carrying germline mutations relevant to CD exhibited dysregulated cell lineage commitment. The development of the human pituitary adenoma organoids represent a paradigm shift in how we model complex pathologies in CD patients that may alter patient care.


For inquiries regarding the contents of this dataset, please contact the Corresponding Author listed in the README.txt file. Administrative inquiries (e.g., removal requests, trouble downloading, etc.) can be directed to data-management@arizona.edu

History

Usage metrics

    Medicine & Health

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC