Transcriptional Responses of In Vitro Blood–Brain Barrier Models to Shear Stress

Foreman, Koji L.; Gastfriend, Benjamin D.; Katt, Moriah E.; Palecek, Sean P.; Shusta, Eric V.

doi:10.3390/biom15020193

This is an early access version, the complete PDF, HTML, and XML versions will be available soon.

Open AccessArticle

Transcriptional Responses of In Vitro Blood–Brain Barrier Models to Shear Stress

by

Koji L. Foreman

¹,

Benjamin D. Gastfriend

^1,†,

Moriah E. Katt

^1,‡

,

Sean P. Palecek

^1,*

and

Eric V. Shusta

^1,2,*

¹

Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA

²

Department of Neurosurgery, University of Wisconsin-Madison, Madison, WI 53792, USA

^*

Authors to whom correspondence should be addressed.

^†

Current address: Departments of Neurosciences and Pharmacology, University of California San Diego, La Jolla, CA 92093, USA.

^‡

Current address: Department of Chemical and Biomedical Engineering, West Virginia University, Morgantown, WV 26506, USA.

Biomolecules 2025, 15(2), 193; https://doi.org/10.3390/biom15020193

Submission received: 19 December 2024 / Revised: 19 January 2025 / Accepted: 22 January 2025 / Published: 29 January 2025

(This article belongs to the Special Issue Barrier Formation and Homeostasis in the Vertebrate Brain)

Download Versions Notes

Abstract

Endothelial cells throughout the body sense blood flow, eliciting transcriptional and phenotypic responses. The brain endothelium, known as the blood–brain barrier (BBB), possesses unique barrier and transport properties, which are in part regulated by blood flow. We utilized RNA sequencing to analyze the transcriptome of primary cultured rat brain microvascular endothelial cells (BMECs), as well as three human induced pluripotent stem cell-derived models. We compared the transcriptional responses of these cells to either low (0.5 dyne/cm²) or high (12 dyne/cm²) shear stresses, and subsequent analyses identified genes and pathways that were influenced by shear including key BBB-associated genes (SLC2A1, LSR, PLVAP) and canonical endothelial shear-stress-response transcription factors (KLF2, KLF4). In addition, our analysis suggests that shear alone is insufficient to rescue the de-differentiation caused by in vitro primary BMEC culture. Overall, these datasets and analyses provide new insights into the influence of shear on BBB models that will aid in model selection and guide further model development.

Keywords: human pluripotent stem cell; blood–brain barrier; shear stress; fluid flow; brain endothelium; transcriptomics

Share and Cite

MDPI and ACS Style

Foreman, K.L.; Gastfriend, B.D.; Katt, M.E.; Palecek, S.P.; Shusta, E.V. Transcriptional Responses of In Vitro Blood–Brain Barrier Models to Shear Stress. Biomolecules 2025, 15, 193. https://doi.org/10.3390/biom15020193

AMA Style

Foreman KL, Gastfriend BD, Katt ME, Palecek SP, Shusta EV. Transcriptional Responses of In Vitro Blood–Brain Barrier Models to Shear Stress. Biomolecules. 2025; 15(2):193. https://doi.org/10.3390/biom15020193

Chicago/Turabian Style

Foreman, Koji L., Benjamin D. Gastfriend, Moriah E. Katt, Sean P. Palecek, and Eric V. Shusta. 2025. "Transcriptional Responses of In Vitro Blood–Brain Barrier Models to Shear Stress" Biomolecules 15, no. 2: 193. https://doi.org/10.3390/biom15020193

APA Style

Foreman, K. L., Gastfriend, B. D., Katt, M. E., Palecek, S. P., & Shusta, E. V. (2025). Transcriptional Responses of In Vitro Blood–Brain Barrier Models to Shear Stress. Biomolecules, 15(2), 193. https://doi.org/10.3390/biom15020193

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

Transcriptional Responses of In Vitro Blood–Brain Barrier Models to Shear Stress

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI