Simple Science

Cutting edge science explained simply

# Biology# Cell Biology

Research Reveals Cell Changes in Mammary Glands

Study highlights how mammary cells adapt in response to their environment.

Nikki K Lytle, Q. Vallmajo-Martin, Z. Ma, S. Srinivasan, D. Murali, C. Dravis, K. Mukund, S. Subramaniam, G. M. Wahl

― 6 min read


Cell Changes in MammaryCell Changes in MammaryResearchand transform.Study reveals how mammary cells adapt
Table of Contents

Mammary Glands are special organs found in mammals that produce milk. The name "mammalia" comes from these glands. A lot of study has been done to understand how these glands work, especially at the cellular level. The new approaches used have shown how cells in the mammary glands can change and adapt. In developing mice, cells from the skin above create a structure called the mammary bulb by a certain day in their growth. After a period of rest, these cells begin to grow rapidly, forming early duct systems that include various Cell Types.

The Development of Mammary Glands

After a mouse is born, its mammary glands quickly develop into two main types of cells. One type can respond to hormones and the other is responsible for making milk. There are also muscle-like cells that form an outer layer. The ducts in the glands continue to grow until the mouse reaches puberty. There are cells at the end of these ducts that help them grow longer. In young mice, the mammary glands grow greatly in response to hormones during pregnancy. This leads to the formation of milk-producing structures. After the young ones are weaned, the mammary glands go through a process called involution, where they shrink back to a pre-pregnancy state.

Stem Cells in Mammary Glands

Early studies indicated that mammary glands could maintain themselves thanks to specific stem cells that last into adulthood. This was shown by transplanting certain cells into cleared areas of fat in mice. However, later studies using new methods have led to different findings. They confirmed the existence of special stem cells in developing mammary glands but also showed that in adults, the different cell types are maintained by more defined cell groups.

The Hypothesis on Cell Transformation

In this study, researchers wanted to see if Basal Cells in the mammary gland could change into a more versatile state when the tissue structure was disrupted. This idea was supported by transplantation studies where damaged tissues led to similar kinds of changes in cells in other organs. These studies indicate that healthy cells can change to help repair tissue when their normal environment is altered.

New Mouse Models for Research

To test the hypothesis, new mouse models were developed that allowed researchers to observe what changes occur at the molecular level. They used a technique called CRISPR to attach fluorescent markers to specific genes in the mammary glands. This allowed for easy identification and analysis of different cell types in the glands.

Observing Cell States in Mice

By using these fluorescent markers, researchers could track and characterize various cell types within the mammary glands. Traditional methods for studying these cells involved using surface markers, but the new models provided a much clearer view of how cells behave during regeneration or when responding to injury.

Analysis of Mammary Tissue

Flow cytometry was then used to analyze the different cell types in the mammary glands. The fluorescent markers in the newly created mice correlated well with traditional markers, confirming their effectiveness. When the fluorescent reporters were used, they accurately showed the presence of specific cell types in both developing and adult mammary tissue.

Identifying Co-expressing Cells

Researchers noticed a small percentage of cells that expressed both basal and luminal markers. These cells were thought to be a potential stem cell population because they could produce both types of cells. To understand their true nature, scientists conducted experiments to see if these co-expressing cells had the ability to regenerate mammary tissues.

Functionality of Co-expressing Cells

When the researchers performed experiments on the co-expressing cells, they found that they showed intermediate characteristics between the two major cell types in the mammary gland. These experiments also indicated that the co-expressing cells were not true stem cells but instead represented a mix of characteristics from both cell types.

Cell Transformations in Laboratory Conditions

Using a special culture system, researchers could transform basal cells into Luminal Cells. This transformation occurred rapidly when basal cells were cultured in three-dimensional conditions designed for mammary cells. The analysis of these cells over time revealed a quick switch where basal cells began expressing luminal markers.

Transplanting Cells into Mice

To further understand the transformations, basal cells from the new reporter mice were transplanted into recipient mice. Within days, these cells began to change and acquire characteristics of luminal cells. This change showed that basal cells could adapt and assume different roles based on their environment.

Molecular Changes During Cell Transition

Using advanced techniques, researchers studied the molecular changes happening within the cells during their transition from basal to luminal states. The analysis suggested that these cells underwent significant changes at the level of gene expression and chromatin structure, positioning themselves for their new identities.

Comparing Different Cell States

Through analyzing various time points post-transplant, researchers discovered a pattern in how cells transitioned from one state to another. They identified specific molecular markers and scoring systems to categorize cells according to their stages of development and similarity to adult cell types.

Understanding the Transition Pathway

The researchers conducted a detailed analysis to understand the pathways that allowed basal cells to transition. They used tools to visualize cell development through time and found that the cells initially appeared to resemble earlier developmental stages before fully adopting luminal characteristics.

Investigating Signaling Pathways

To learn more about how these transitions occur, the researchers explored various signaling pathways known to be important in other developmental processes. They identified changes in several pathways, including those linked to cell growth and survival, and looked into how these pathways influenced the transition from basal to luminal cells.

The Role of Specific Genes

Further investigation revealed that certain genes associated with signaling pathways were upregulated during the transitions. These findings pointed to a complex network of interactions that helped guide the cells as they changed.

Functional Testing of Pathways

To see how these pathways worked in practice, researchers conducted experiments using different inhibitors to block the signals responsible for cell transitions. The results showed that inhibiting certain pathways significantly affected the efficiency of basal-to-luminal transitions.

Comparing Natural and Induced Changes

Researchers compared their findings with previous studies that looked at similar processes in the mammary glands. They found that many of the mechanisms identified in this study mirrored those seen during natural events, highlighting the importance of understanding these transitions in broader biological contexts.

Implications for Cancer Research

The study concluded by discussing the potential implications for understanding breast cancer. The transient hybrid states observed during cell transitions might play a role in the development of breast tumors. The authors suggested that this research could provide insights into how cancer cells behave and develop over time.

Conclusion

Overall, this research sheds light on the mechanisms by which mammary cells adapt and change in response to their environment. The findings offer a better understanding of how these cells can regenerate and maintain mammary function, as well as the possible connections to disease processes like cancer. The new mouse models and techniques developed for this study provide valuable tools for future research in this area, and the insights gained could lead to advances in regenerative medicine and cancer treatment strategies.

Original Source

Title: The molecular chronology of mammary epithelial cell fate switching

Abstract: The adult mammary gland is maintained by lineage-restricted progenitor cells through pregnancy, lactation, involution, and menopause. Injury resolution, transplantation-associated mammary gland reconstitution, and tumorigenesis are unique exceptions, wherein mammary basal cells gain the ability to reprogram to a luminal state. Here, we leverage newly developed cell-identity reporter mouse strains, and time-resolved single-cell epigenetic and transcriptomic analyses to decipher the molecular programs underlying basal-to-luminal fate switching in vivo. We demonstrate that basal cells rapidly reprogram toward plastic cycling intermediates that appear to hijack molecular programs we find in bipotent fetal mammary stem cells and puberty-associatiated cap cells. Loss of basal-cell specifiers early in dedifferentiation coincides with activation of Notch and BMP, among others. Pharmacologic blockade of each pathway disrupts basal-to-luminal transdifferentiation. Our studies provide a comprehensive map and resource for understanding the coordinated molecular changes enabling terminally differentiated epithelial cells to transition between cell lineages and highlights the stunning rapidity by which epigenetic reprogramming can occur in response to disruption of tissue structure.

Authors: Nikki K Lytle, Q. Vallmajo-Martin, Z. Ma, S. Srinivasan, D. Murali, C. Dravis, K. Mukund, S. Subramaniam, G. M. Wahl

Last Update: 2024-11-04 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.10.08.617155

Source PDF: https://www.biorxiv.org/content/10.1101/2024.10.08.617155.full.pdf

Licence: https://creativecommons.org/licenses/by/4.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

More from authors

Similar Articles