The surprising diversity of the fallopian tube
A study provides a new cell atlas of the female reproductive organ

Date:
March 28, 2022
Source:
Michigan Medicine - University of Michigan
Summary:
A new study creates a detailed 'atlas' of the various cell types
and their gene activities within the highly specialized fallopian
tube, paving the way for new research into infertility and other
diseases affecting this organ, including some cancers.



FULL STORY ==========================================================================
The fallopian tube is the site of fertilization, where once a month for
the duration of a female's post-pubescent, pre-menopausal life, an egg
is moved from the ovary, ready for fertilization by a sperm cell.


==========================================================================
A new study from Michigan Medicine researchers creates a detailed
"atlas" of the various cell types and their gene activities within the
highly specialized fallopian tube, paving the way for new research
into infertility and other diseases affecting this organ, including
some cancers.

Using tissue samples from four premenopausal women, Saher Sue Hammoud,
Ph.D., and Jun Li, Ph.D. from the Department of Human Genetics led a team
at U-M to analyze almost 60,000 cells by single-cell RNA sequencing. They
used the data to characterize the diversity of cells that make up the
fallopian tube, including both the lining of the tube (the epithelium)
and the deeper stromal layer, consisting of immune, blood, muscle,
and other cells.

Hammoud and Li are joined by Ariella Shikanov, Ph.D., of the Department
of Biomedical Engineering, Erica Marsh, M.D., of the Department of
Obstetrics and Gynecology, and team members Nicole Ulrich, M.D.,
Yu-chi Shen, Ph.D., and Qianyi Ma, Ph.D. Their project is part of the
Human Cell Atlas Seed Networks, an international effort supported by
the Chan-Zuckerberg Initiative to map all cells in the human body as a
resource for better understanding health and disease.

Prior to their work, "it was known that there are about four epithelial
cell types in the fallopian tube," said Hammoud. "We were able to reveal
a deeper level of heterogeneity within these cells." Specifically,
they identified 10 epithelial cell subtypes, including four of the
finger-like ciliated cells responsible for moving the egg through the
fallopian tube's three sections before and after fertilization.



==========================================================================
The cells within the fallopian tube are ever changing, replenishing
themselves over time and varying in number depending on a woman's age, hormones, menstrual cycle, and in the presence of disease. By comparing
cells from women with healthy fallopian tubes to two samples from women
with a fallopian tube disease known as hydrosalpinx (conventionally known
as a blocked fallopian tube), the researchers were able to pinpoint
which cells increased in number, and which changed characteristics,
such as a high degree of inflammation.

"Some of the cells are the cause of the disease state, and some others are
the consequence; and now we know the patterns for individual cell types
to figure out the molecular reasons for that pathology," commented Li.

Precursor cells in the tube and cancer connection? The team also found
that some of the cell subtypes they defined in the fallopian tube may
function as precursor cells, those that can regenerate multiple cell
types in response to normal tissue turnover, or for repairing a damage.

One of the most surprising findings of the study, says Hammoud, was the discovery of cells with markers for epithelial-mesenchymal transition,
also known as EMT, a process not previously associated with the fallopian
tube, through which a cell can, under certain circumstances, become
cancerous.



========================================================================== Ovarian cancer, it turns out, may be a misnomer. The new study adds
to accumulating evidence that the root of ovarian cancer -- the fifth
leading cause of cancer death in women -- may originate within the
adjacent fallopian tube.

"The EMT process seems to be tightly regulated in the pre-menopausal
woman," she said. "One possible connection to cancer is that when there is misregulation in this population of cells in some unfortunate individuals,
they may develop ovarian cancer. With EMT cells in the fallopian tube,
you do have the predisposition right there." Additional insights came
from the fallopian tube cells from women with hydrosalpinx, specifically,
that the disease may lead to a type of scarring called fibrosis. The implication is that for women who don't want to have their tubes removed,
"you could think about treating them with anti-fibrotic drugs such as
the ones used to treat lung fibrosis as a way to save their tubes during reproductive age," noted Hammoud.

Compared to past efforts, the study provides much more detailed
information about cell types and functions in the tube for researchers interested in a host of questions about the normal female reproductive
system. "This really is a basecamp to launch future studies," says Li, including ones that look at the effects of age, the menstrual cycle,
hormone therapy, and ancestral background on cellular diversity and
disease pathology.

Additional authors on the paper include Kun Yang, D. Ford Hannum, Andrea
Jones, Jordan Machlin, John F. Randolph Jr, Yolanda R. Smith, Samantha
B. Schon, Richard Lieberman, Stephen J. Gurczynski, and Bethany B. Moore.


========================================================================== Story Source: Materials provided by
Michigan_Medicine_-_University_of_Michigan. Original written by Kelly
Malcom. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Nicole D. Ulrich, Yu-chi Shen, Qianyi Ma, Kun Yang, D. Ford Hannum,
Andrea Jones, Jordan Machlin, John F. Randolph, Yolanda
R. Smith, Samantha B. Schon, Ariella Shikanov, Erica E. Marsh,
Richard Lieberman, Stephen J. Gurczynski, Bethany B. Moore,
Jun Z. Li, Sue Hammoud. Cellular heterogeneity of human
fallopian tubes in normal and hydrosalpinx disease states
identified using scRNA-seq. Developmental Cell, 2022; DOI:
10.1016/j.devcel.2022.02.017 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220328112719.htm

--- up 4 weeks, 10 hours, 50 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)