Expandable Arterial Endothelial Precursors from Human CD34+ Cells Differ in Their Proclivity to Undergo an Endothelial-to-Mesenchymal Transition

Summary: Arterial diseases continue to pose a major health concern but in vitro studies are limited because explanted cells can exhibit poor proliferative capacity and a loss of specificity. Here, we find that two transcription factors, MYCN and SOX17, induce and indefinitely expand in culture precu...

Full description

Bibliographic Details
Main Authors: Auston Z. Miller, Alexander Satchie, Alex P. Tannenbaum, Aman Nihal, James A. Thomson, David T. Vereide
Format: Article
Language:English
Published: Elsevier 2018-01-01
Series:Stem Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2213671117305593
_version_ 1818204044675514368
author Auston Z. Miller
Alexander Satchie
Alex P. Tannenbaum
Aman Nihal
James A. Thomson
David T. Vereide
author_facet Auston Z. Miller
Alexander Satchie
Alex P. Tannenbaum
Aman Nihal
James A. Thomson
David T. Vereide
author_sort Auston Z. Miller
collection DOAJ
description Summary: Arterial diseases continue to pose a major health concern but in vitro studies are limited because explanted cells can exhibit poor proliferative capacity and a loss of specificity. Here, we find that two transcription factors, MYCN and SOX17, induce and indefinitely expand in culture precursors of human arterial endothelial cells (expandable arterial endothelial precursors [eAEPs]). The eAEPs are derived from CD34+ cells found in umbilical cord blood or adult bone marrow. Independent eAEP lines differ in their proclivity to undergo an endothelial-to-mesenchymal transition (EndoMT), a hallmark event in a broad array of vascular diseases and disorders. Some cell lines spontaneously become mesenchymal over time in culture, an effect exacerbated by inhibition of the fibroblast growth factor receptor, while others do not readily convert. These distinctions were exploited to identify genes that correlate with resistance to an EndoMT and to elucidate transcriptional changes that underpin the transition.
first_indexed 2024-12-12T03:34:59Z
format Article
id doaj.art-d9c44a1aad6b4790860c335842d05648
institution Directory Open Access Journal
issn 2213-6711
language English
last_indexed 2024-12-12T03:34:59Z
publishDate 2018-01-01
publisher Elsevier
record_format Article
series Stem Cell Reports
spelling doaj.art-d9c44a1aad6b4790860c335842d056482022-12-22T00:39:49ZengElsevierStem Cell Reports2213-67112018-01-01101738610.1016/j.stemcr.2017.12.011Expandable Arterial Endothelial Precursors from Human CD34+ Cells Differ in Their Proclivity to Undergo an Endothelial-to-Mesenchymal TransitionAuston Z. Miller0Alexander Satchie1Alex P. Tannenbaum2Aman Nihal3James A. Thomson4David T. Vereide5Morgridge Institute for Research, Madison, WI 53715, USAMorgridge Institute for Research, Madison, WI 53715, USAMorgridge Institute for Research, Madison, WI 53715, USAMorgridge Institute for Research, Madison, WI 53715, USAMorgridge Institute for Research, Madison, WI 53715, USA; Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, USAMorgridge Institute for Research, Madison, WI 53715, USA; Corresponding authorSummary: Arterial diseases continue to pose a major health concern but in vitro studies are limited because explanted cells can exhibit poor proliferative capacity and a loss of specificity. Here, we find that two transcription factors, MYCN and SOX17, induce and indefinitely expand in culture precursors of human arterial endothelial cells (expandable arterial endothelial precursors [eAEPs]). The eAEPs are derived from CD34+ cells found in umbilical cord blood or adult bone marrow. Independent eAEP lines differ in their proclivity to undergo an endothelial-to-mesenchymal transition (EndoMT), a hallmark event in a broad array of vascular diseases and disorders. Some cell lines spontaneously become mesenchymal over time in culture, an effect exacerbated by inhibition of the fibroblast growth factor receptor, while others do not readily convert. These distinctions were exploited to identify genes that correlate with resistance to an EndoMT and to elucidate transcriptional changes that underpin the transition.http://www.sciencedirect.com/science/article/pii/S2213671117305593self-renewalarterial endothelial precursorsendothelial-to-mesenchymal transitionMYCNSOX17transcription factors
spellingShingle Auston Z. Miller
Alexander Satchie
Alex P. Tannenbaum
Aman Nihal
James A. Thomson
David T. Vereide
Expandable Arterial Endothelial Precursors from Human CD34+ Cells Differ in Their Proclivity to Undergo an Endothelial-to-Mesenchymal Transition
Stem Cell Reports
self-renewal
arterial endothelial precursors
endothelial-to-mesenchymal transition
MYCN
SOX17
transcription factors
title Expandable Arterial Endothelial Precursors from Human CD34+ Cells Differ in Their Proclivity to Undergo an Endothelial-to-Mesenchymal Transition
title_full Expandable Arterial Endothelial Precursors from Human CD34+ Cells Differ in Their Proclivity to Undergo an Endothelial-to-Mesenchymal Transition
title_fullStr Expandable Arterial Endothelial Precursors from Human CD34+ Cells Differ in Their Proclivity to Undergo an Endothelial-to-Mesenchymal Transition
title_full_unstemmed Expandable Arterial Endothelial Precursors from Human CD34+ Cells Differ in Their Proclivity to Undergo an Endothelial-to-Mesenchymal Transition
title_short Expandable Arterial Endothelial Precursors from Human CD34+ Cells Differ in Their Proclivity to Undergo an Endothelial-to-Mesenchymal Transition
title_sort expandable arterial endothelial precursors from human cd34 cells differ in their proclivity to undergo an endothelial to mesenchymal transition
topic self-renewal
arterial endothelial precursors
endothelial-to-mesenchymal transition
MYCN
SOX17
transcription factors
url http://www.sciencedirect.com/science/article/pii/S2213671117305593
work_keys_str_mv AT austonzmiller expandablearterialendothelialprecursorsfromhumancd34cellsdifferintheirproclivitytoundergoanendothelialtomesenchymaltransition
AT alexandersatchie expandablearterialendothelialprecursorsfromhumancd34cellsdifferintheirproclivitytoundergoanendothelialtomesenchymaltransition
AT alexptannenbaum expandablearterialendothelialprecursorsfromhumancd34cellsdifferintheirproclivitytoundergoanendothelialtomesenchymaltransition
AT amannihal expandablearterialendothelialprecursorsfromhumancd34cellsdifferintheirproclivitytoundergoanendothelialtomesenchymaltransition
AT jamesathomson expandablearterialendothelialprecursorsfromhumancd34cellsdifferintheirproclivitytoundergoanendothelialtomesenchymaltransition
AT davidtvereide expandablearterialendothelialprecursorsfromhumancd34cellsdifferintheirproclivitytoundergoanendothelialtomesenchymaltransition