Strict lineage tracing crucial to nerve cell regeneration research


Date:
September 29, 2021
Source:
UT Southwestern Medical Center
Summary:
Stem cell scientists find that stringent lineage tracing is crucial
for studies of nerve cell regeneration.



FULL STORY ==========================================================================
UT Southwestern stem cell scientists find that stringent lineage tracing
is crucial for studies of nerve cell regeneration. Their results, which
are published in Cell, show that this tracing is far from routine in the
field and suggest that earlier studies reporting "striking" regeneration results must be reexamined.


========================================================================== Lineage tracing, which is a fundamental approach in developmental biology, refers to tests used to map out the progeny -- or descendants -- of a
given cell in an organism.

Lineage tracing is also central to the field of stem cell biology, so
it was surprising to learn how often such testing had been omitted, the
authors write in the newly published study in Cell. The two corresponding authors are Chun-Li Zhang, Ph.D., a Professor of Molecular Biology and
a W.W. Caruth, Jr. Scholar in Biomedical Research; and Lei-Lei Wang,
Ph.D., an Instructor of Molecular Biology and member of the Zhang lab,
which studies nerve cell regeneration in the brain and spinal cord.

"We have from the start employed the most stringent methods to analyze
nerve cell regeneration. It was therefore astonishing to read a number
of other papers -- including some that make phenomenal claims -- that
failed to do careful analyses," said Dr. Zhang, a member of the Hamon
Center for Regenerative Science and Medicine at UT Southwestern.

After running dozens of experiments using a range of protocols, the
researchers identified which specific lineage tracing assays appeared most robust and reliable -- the so-called gold standard tests. "We employed the currently available lineage tracing assays. No new ones were developed,"
Dr. Zhang said.

The scientists also identified tests that were less likely to provide
precise results.

The study concludes by listing reliable lineage tracing tests and strongly recommending these assays be used in all laboratories doing nerve cell regeneration research. "The methods we list are straightforward to
establish in a laboratory, and we believe they should always be used,"
he said.

Dr. Zhang received his Ph.D. in genetics and development from UT
Southwestern Medical Center, where he worked on muscle development and
heart disease. He conducted postdoctoral research on neural stem cells
as a Howard Hughes Medical Institute Fellow of the Life Sciences Research Foundation at the Salk Institute in La Jolla, California.

At UT Southwestern, Dr. Zhang's laboratory has reported several advances
in neural stem cell biology, such as regeneration of the brain and spinal
cord in mice following injury. The Scientistrecognized his lab's work on
cell fate reprogramming in live animals as one of 2014's Big Advances in Science. He won a National Institutes of Health Director's New Innovator
Award in 2009.

Using rigorous lineage tracing, the team of Drs. Wang and Zhang reported
in 2018 that while attempting to transform a type of brain cell known as
a glial cell into a neuron, they instead reprogrammed mature inhibitory
neurons into a different type of neuron that produces the neurotransmitter
lost in Parkinson's disease. Their study indicated that the brain's
neurons were more malleable in adulthood than previously thought.

Earlier this year, they reported in Cell Stem Cell that the latent
neurogenic potential of glial cells can be leveraged to produce new
neurons and lead to functional recovery after spinal cord injury in mice.

UTSW co-authors include: Carolina Serrano Garcia, Xiaoling Zhong,
Shuaipeng Ma, and Yuhua Zou.

The Welch Foundation supported the study (I-1724), as did the Decherd Foundation, the Kent Waldrep Foundation Center for Basic Research on
Nerve Growth and Regeneration, the Texas Alzheimer's Research and Care Consortium (TARCC2020), and the NIH (NS099073, NS092616, NS111776,
NS117065, and NS088095).

========================================================================== Story Source: Materials provided by UT_Southwestern_Medical_Center. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Lei-Lei Wang, Carolina Serrano, Xiaoling Zhong, Shuaipeng Ma,
Yuhua Zou,
Chun-Li Zhang. Revisiting astrocyte to neuron conversion with
lineage tracing in vivo. Cell, 2021; DOI: 10.1016/j.cell.2021.09.005 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210929125803.htm

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