A simpler way to make sensory hearing cells

Date:
July 1, 2020
Source:
Keck School of Medicine of USC
Summary:
Scientists are whispering the secrets of a simpler way to generate
the sensory cells of the inner ear. Their approach uses direct
reprogramming to produce sensory cells known as 'hair cells,'
due to their hair-like protrusions that sense sound waves.



FULL STORY ========================================================================== Scientists from the USC Stem Cell laboratories of Neil Segil and Justin
Ichida are whispering the secrets of a simpler way to generate the
sensory cells of the inner ear. Their approach uses direct reprogramming
to produce sensory cells known as "hair cells," due to their hair-like protrusions that sense sound waves. The study was published in the
journal eLife.


========================================================================== "We've succeeded in directly reprogramming a variety of mouse cell
types into what we're calling 'induced hair cell-like cells, or iHCs,"
said PhD student Louise Menendez, the study's lead author. "This allows
us to efficiently generate large numbers of iHCs to identify causes and treatments for hearing loss." The scientists successfully reprogrammed
three different types of mouse cells to become iHCs. The first two
types were embryonic and adult versions of connective tissue cells,
known as fibroblasts. The third was a different type of inner ear cell,
known as a supporting cell.

To achieve reprogramming, the scientists exposed fibroblasts and
supporting cells to a cocktail of four transcription factors, which
are molecules that help convey the instructions encoded in DNA. The
scientists identified this cocktail by testing various combinations of
16 transcription factors that were highly active in the hair cells of
newborn mice.

"The four key ingredients turned out to be the transcription factors Six1, Atoh1, Pou4f3, and Gfi1," said Menendez.

The resulting iHCs resembled naturally occurring hair cells in terms
of their structure, electrophysiology, and genetic activity. The iHCs
also possessed several other distinct characteristics of hair cells,
including vulnerability to an antibiotic known to cause hearing loss.

"Hair cells are easy to damage, and currently impossible to repair in
humans," said Segil, a professor in the Department of Stem Cell Biology
and Regenerative Medicine, and the USC Tina and Rick Caruso Department
of Otolaryngology -- Head and Neck Surgery, and one of the corresponding authors of the study. "Aging, loud noises, and certain chemotherapy drugs
and antibiotics can all lead to the permanent loss of hair cells, which
is the leading contributor to hearing loss worldwide." iHCs have the
potential to accelerate hearing loss research in at least two important
ways, according to Ichida, who is the John Douglas French Alzheimer's Foundation Associate Professor of Stem Cell Biology and Regenerative
Medicine at USC, and the other corresponding author of the study.

"In the near term, researchers can use iHCs to screen large numbers of
drug candidates that might prevent or treat hearing loss," said Ichida,
who is also a New York Stem Cell Foundation-Robertson Investigator. "And further in the future, it could become possible to directly reprogram supporting cells in the inner ear of a deafened individual, as a way to
restore hearing."

========================================================================== Story Source: Materials provided by
Keck_School_of_Medicine_of_USC. Original written by Cristy Lytal. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Louise Menendez, Talon Trecek, Suhasni Gopalakrishnan, Litao Tao,
Alexander L Markowitz, Haoze V Yu, Xizi Wang, Juan Llamas,
Chichou Huang, James Lee, Radha Kalluri, Justin Ichida, Neil
Segil. Generation of inner ear hair cells by direct lineage
conversion of primary somatic cells.

eLife, 2020; 9 DOI: 10.7554/eLife.55249 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200701134242.htm

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