Early in human development, during the first trimester of gestation, a fetus may have XX or XY chromosomes that indicate its sex. Yet at this stage a mass of cells known as the bipotential gonad that ultimately develops into either ovaries or testes has yet to commit to its final destiny.
While researchers had studied the steps that go into the later stages of this process, little has been known about the precursors of the bipotential gonad. In a new study published in Cell Reports and co-led by Kotaro Sasaki of Penns School of Veterinary Medicine, an international team lays out the detailed development of this key facet of sexual determination in two mammalian models.
Using single-cell transcriptome data, we can get a lot of information about gene expression at each developmental stage, says Sasaki. We can define what the default process is and how it might go awry in some cases. This has never been done in traditional developmental biology. Now we can understand development in molecular terms.
Disorders of sex development (DSD) occur when internal and external reproductive structures develop differently from what would be expected based on an individuals genetics. For example someone with XY chromosomes might develop ovaries. These conditions often affect fertility and are associated with an increased risk of germ cell tumors.
These disorders oftentimes create psychological and physical distress for patients, Sasaki says. Thats why understanding gonadal development is important.
To understand atypical development, Sasaki and colleagues in the current study sought to layout the steps of typical development, working with a mouse model and a monkey model.
The researchers began by examining mouse embryos throughout embryonic development, using molecular markers to track the location of different proteins suspected to be involved in the formation of reproductive structures. They noticed that by day nine of a mouses embryonic development, a structure called the posterior intermediate mesoderm (PIM) lit up brightly with the marker for a gene critical to the development of gonads, kidneys, and the hormone-producing adrenal glands, which are located adjacent to the kidneys.
Zeroing in on the PIM and its progeny cells, the team found that, by day 10.5, these also expressed a marker known to be associated with the bipotential gonad.
People have previously studied the origin of the urogenital organs and the kidney and based on that believed that their origins were very close, Sasaki says. So our hypothesis was that the PIM was the origin of the gonads as well as the kidneys.
To identify the origin of the gonad, they performed lineage tracing, in which scientists label cells in order to track their descendents, which indeed supported the connection between the PIM and the gonads.
To further confirm that the PIM played a similar role in an organism closer to humans in reproductive biology, the researchers made similar observations in embryos from cynomolgus monkeys. Though the developmental timing was different from the mouse, as was expected, the PIM again appeared to give rise to the bipotential gonad.
Digging even deeper into the molecular mechanism of the transition between the PIM and bipotential gonad, the researchers used a cutting-edge technique: single-cell sequencing analysis, whereby they can identify which genes are being turned on during each developmental stage.
Not only were they able to identify genes that were turned onmany of which had never before been associated with reproductive developmentbut they observed a transition state between the PIM and bipotential gonad, called the coelomic epithelium. Comparing the mice and monkey embryos, the researchers came up with a group of genes that were conserved, or shared between the species. Some of these genes are already known to be important for the development of mouse and human ovaries and testes, Sasaki says, and some have been implicated in the development of DSDs.
He notes that in roughly half of patients with DSDs, however, the genetic cause is unknown. So this database were assembling may now be used to predict some additional genes that are important in DSD and could be used for screening and diagnosis of DSDs, or even treatment and prevention.
The study also illuminated the relationship between the origin of the kidneys, adrenal glands, and gonads. They all originate from the PIM, but the timing and positioning is different, Sasaki says.
The adrenal glands, he says, develop from the anterior portion of the PIM, or that section closer to the head and arise early, while the kidney arises later from the posterior portion of the PIM. The gonadal glands span the PIM, with some regions developing earlier and others later.
In future studies, Sasaki and colleagues would like to continue teasing out the details and stages of gonadal development. Sasakis ultimate goal is to coax a patients own stem cells to grow into reproductive organs in the lab.
Some patients with DSDs dont have ovaries and testes, and some cancer patients undergo chemotherapy and completely lose their ovary function, Sasaki says. If you could induce a stem cell to grow into an ovary in the lab, you could provide a replacement therapy for these patients, allowing them to regain normal hormone levels and even fertility. With a precise molecular map to the developing gonad in hand, we are now one step closer to the this goal.
Kotaro Sasaki is an assistant professor in the Department of Biomedical Sciences in the University of Pennsylvania School of Veterinary Medicine.
Sasakis coauthors on the study were Penns Keren Cheng and Yasunari Seita; Kyoto Universitys Akiko Oguchi, Yasuhiro Murakawa, Ikuhiro Okamoto, Hiroshi Ohta, Yukihiro Yabuta, Takuya Yamamoto, and Mitinori Saitou; and Shiga University of Medical Sciences Chizuru Iwatani and Hideaki Tsuchiya. Sasaki and Saitou were corresponding authors.
The study was supported by a JST-ERATO Grant (JPMJER1104), Grant-in-Aid for Specially Promoted Research from JSPS (17H06098), the Pythias Fund, and the Open Philanthropy Fund from Silicon Valley Community Foundation (2019-197906).
Here is the original post:
The origin of reproductive organs | Penn Today - Penn Today
- Secret to eternal youth? John Cleese extols virtues of stem cell treatment - The Guardian - April 26th, 2024
- Cabinet approves two bills on regenerative medicine - - April 26th, 2024
- Parental Fury After Stem Cell Bank Ruins Thousands of Samples in Singapore - Bloomberg - April 24th, 2024
- Pressure in the womb may influence facial development - Phys.org - April 24th, 2024
- Circadian regulation of cancer stem cells and the tumor microenvironment during metastasis - Nature.com - April 24th, 2024
- Shinobi strikes deal with electronics powerhouse Panasonic to create new cell therapy manufacturing platform - FiercePharma - April 19th, 2024
- The Stem Cells Market expected to grow at the value of USD 28.1 Billion by 2030 with a 10.48% CAGR. - WhaTech - April 19th, 2024
- Scientists produce in vitro model of cell differentiation during early facial development - Phys.org - April 19th, 2024
- Somite: AI-Based Stem Cell Therapy Company Closes $5.3 Million In Funding - Pulse 2.0 - April 19th, 2024
- Paralyzed man who can walk again shows potential benefit of stem cell therapy - ABC News - April 5th, 2024
- Stem Cells Market Innovations Investigated by Industry Overview and Global Forecast - WhaTech - April 5th, 2024
- New tool provides researchers with improved understanding of stem cell aging in the brain - University of Wisconsin-Madison - April 1st, 2024
- The PTM profiling of CTCF reveals the regulation of 3D chromatin structure by O-GlcNAcylation - Nature.com - April 1st, 2024
- Signatures of Autofluorescence Used To Study Stem Cells Aging in the Brain - Technology Networks - March 30th, 2024
- Two decades of embryonic stem cells: a historical overview - March 28th, 2024
- Researchers at Phoenix Children's First in the World to Produce Mouse Lungs in Rats - The Malaysian Reserve - March 26th, 2024
- Unlocking the mysteries of early human development through blastoid models - News-Medical.Net - March 24th, 2024
- Unlocking the Secrets of Aging: Researchers Reveal Key to Intestinal Balance - SciTechDaily - March 17th, 2024
- Human stem-cell-based therapy for Parkinson's disease proven safe PET - BioNews - March 13th, 2024
- Exploring the inner workings of stem cells: When location changes the message - Phys.org - March 9th, 2024
- Confronting IVF: Human Embryos Are Persons With a Right to Life - Walter Bradley Center for Natural and Artificial Intelligence - March 7th, 2024
- When Location Changes the Message - UConn Today - University of Connecticut - March 7th, 2024
- Distinct pathways drive anterior hypoblast specification in the implanting human embryo - Nature.com - March 6th, 2024
- In light of the Alabama court ruling, a look at the science of IVF : Short Wave - NPR - March 3rd, 2024
- The weird way Alabamas embryo ruling takes on artificial wombs - MIT Technology Review - February 25th, 2024
- Alabama's biggest hospital to suspend transfer of embryos after court ruling - ABC News - February 24th, 2024
- Stem Cells: FAQs Answered for Patients and Caregivers - Corporate Wellness Magazine - February 22nd, 2024
- Charles River Collaborates with Pluristyx, Expanding its Portfolio of Human Pluripotent Stem Cells - Business Wire - February 22nd, 2024
- Breakthrough Stem Cell Treatments for Stroke Recovery: What You Need to Know - Medical Tourism Magazine - February 20th, 2024
- Global Cell Isolation Market Size To Worth USD 13.4 Billion By 2033 | CAGR of 12.5% - Yahoo Finance - February 20th, 2024
- The Mechanism of Positional Cues in Embryonic Development and Signaling Molecules in Cell Fate - Medriva - February 18th, 2024
- Regeneration of the Retina Using Pluripotent Stem Cells: A Comprehensive Review - Cureus - February 5th, 2024
- CRISPR/Cas9-mediated deletion of a GA-repeat in human GPM6B leads to disruption of neural cell differentiation from ... - Nature.com - January 29th, 2024
- Global Human Embryonic Stem Cell Market Analysis 2024-2034: A Deep Dive into Applications, End-users, and ... - GlobeNewswire - January 26th, 2024
- No, Rep. Steve Scalise Didn't Vote Against Stem Cell Research From Which He Is Now Benefiting - Yahoo News - January 14th, 2024
- Clinical applications of stem cell-derived exosomes | Signal Transduction and Targeted Therapy - Nature.com - January 12th, 2024
- How Stem Cell Embryo Models Won Method of the Year - Technology Networks - January 12th, 2024
- Changing the public perception of human embryology - ESHRE - January 11th, 2024
- How the Human Body Regenerates New Cells Every Year - Laughing Squid - January 4th, 2024
- Lab-grown models of embryos increasingly resemble the real thing | Mint - Mint - January 4th, 2024
- Singapore should ban reproductive applications of synthetic human embryos - BioEdge - January 4th, 2024
- Machine learning-based estimation of spatial gene expression pattern during ESC-derived retinal organoid ... - Nature.com - December 21st, 2023
- The development of embryos may be less shaped by genes than we thought - New Scientist - December 21st, 2023
- Embryonic stem cell - Wikipedia - December 13th, 2023
- Researchers discover a mechanism that controls the identity of stem cells - Phys.org - December 9th, 2023
- 'Fascinating and completely unexpected': Tiny robots fix neurons - FierceBiotech - December 5th, 2023
- Establishment and characterization of matched immortalized human ... - Nature.com - December 5th, 2023
- Proteomic insights into the associations between obesity, lifestyle ... - BMC Medicine - December 5th, 2023
- New therapy can treat rare and hereditary diseases - ScienceNorway - December 5th, 2023
- Scientists Still Can't Be Trusted on Gene Editing - Progressive.org - December 5th, 2023
- Harvard Apparatus Regenerative Technology and Renowned ... - Yahoo Finance - December 5th, 2023
- 4.4 Million Funding Injection Fuels World-Class Bioscience Research Programme - India Education Diary - December 3rd, 2023
- A two-kinesin mechanism controls neurogenesis in the developing ... - Nature.com - December 3rd, 2023
- What happens when nature and cities collide - CNN - December 3rd, 2023
- Pro-Life This Week: December 1, 2023 | ALL - All.org - December 3rd, 2023
- A look at the international race to create human eggs and sperm in ... - NPR - December 1st, 2023
- Synthetic genetic circuits to uncover the OCT4 trajectories of ... - Science - December 1st, 2023
- Why the Novo Nordisk Foundation is betting big on stem cells - pharmaphorum - November 29th, 2023
- Charity Watchlist Helps Donors Ensure Their Year-End Gifts Don't ... - All.org - November 29th, 2023
- A green glowing monkey has been created in China. What were the ... - Genetic Literacy Project - November 29th, 2023
- Fetal Bovine Serum Market to reach USD 1.26 Bn by 2029, emerging at a CAGR of 5.3 percent according to a ne... - WhaTech Technology and Markets News - November 29th, 2023
- Implications of Gene Therapy in Dentistry and Periodontics: A ... - Cureus - November 27th, 2023
- Study shows how to treat hereditary, rare diseases - ETHealthWorld - November 27th, 2023
- Drugs identified that may reverse brain fog caused by COVID-19 - New Atlas - November 27th, 2023
- The genes that made us truly human may also make us ill - BBC.com - November 25th, 2023
- Therapy to treat rare, hereditary diseases: Study - Hindustan Times - November 25th, 2023
- How the growth of a giant single cell is intertwined with daily self-rhythms - Phys.org - November 25th, 2023
- On this day: Mahmoud Abbas becomes leader of Fatah in 2004 - In-Cyprus - November 25th, 2023
- Evaluation of A-ring hydroxymethylene-amino- triterpenoids as ... - Nature.com - November 25th, 2023
- Disruption of the autism gene and chromatin regulator KDM5A alters ... - Science - November 23rd, 2023
- Scientists Created a Monkey With Two Different Sets of DNA - Smithsonian Magazine - November 23rd, 2023
- Genomic tug of war could boost cancer therapy - Science Daily - November 23rd, 2023
- What are stem cells? Throw light on various types of stem cells and ... - Insights IAS - November 23rd, 2023
- The Paul G. Allen Family Foundation awards $10.5 million to new ... - EurekAlert - November 23rd, 2023
- Daily briefing: Why these PhD scientists went into teaching - Nature.com - November 23rd, 2023
- Innovative Therapy Targets Rare, Hereditary Diseases - Mirage News - November 23rd, 2023
- Scientists uncover "genomic tug of war" that influences ... - News-Medical.Net - November 21st, 2023
- DOT1L is a barrier to histone acetylation during reprogramming to ... - Science - November 21st, 2023
- Tumor microenvironment composition & related therapy in HCC | JHC - Dove Medical Press - November 21st, 2023
- T-Therapeutics raises $59M in series A for T-cell receptors - BioWorld Online - November 19th, 2023
Recent Comments