Smooth Move

In the mouse lung, hardening of a blood vessel can result from just a single progenitor cell forming new smooth muscle.

By | January 1, 2016

PATHOLOGICAL PIONEERS: In low-oxygen conditions, smooth muscle cells in the arteriole of a mouse migrate distally (red and blue cells).COURTESY OF A. SHEIKH AND D. GREIF, YALE UNIVERSITY


The paper
A.Q. Sheikh et al., “Smooth muscle cell progenitors are primed to muscularize in pulmonary hypertension,” Sci Transl Med, 7:308ra159, 2015.

The sleeve
Blood vessels are surrounded by a layer of smooth muscle that helps regulate blood flow. In healthy lungs, this muscular sleeve ends midway along the length of arterioles, which branch into capillaries. In pulmonary hypertension (PH), however, the muscle extends distally toward the capillary bed and stiffens the vessel.

The migration
Previous research in mice from Yale University’s Daniel Greif and colleagues found that oxygen deprivation (hypoxia), which can cause PH in humans and animal models, leads smooth muscle cells (SMCs) in the proximal and middle arteriole to dedifferentiate, migrate distally, and redifferentiate to form new muscle. The researchers also found that, among these proximal SMCs, a few cells expressed a dedifferentiation marker called PDGFR-β.

The expansion
To find out if and how these PDGFR-β-expressing cells contribute to extra muscle distally, Greif’s postdoc Abdul Sheikh labeled and tracked them in mice. Under hypoxic conditions these cells gave rise to the distal musculature as if “primed” to do so. Although each arteriole has one to three primed cells, only one cell migrates, the researchers found. It then clonally expands to coat the distal vessel with SMCs.

The clonal expansion “is really a fascinating discovery that they’ve made,” says University of Virginia School of Medicine’s Gary Owens. “It’s the coolest paper I’ve read in some time.”

The applications
Greif says the group’s finding is “particularly exciting” because it suggests that this pathological muscle arises from a small number of specific progenitors, which could potentially be targets for treatments.

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