洞察 - Cell Biology - # Regulation of Tracheal Stem Cell Migration by Fat Body-Derived Cytokine Upd2

Fat Body-Derived Cytokine Upd2 Regulates the Directional Migration of Tracheal Stem Cells in Drosophila

Q: How might the findings from this study on Drosophila tracheal stem cells be applicable to the regulation of stem cell migration in other organisms, including mammals?

The findings from this study on Drosophila tracheal stem cells provide significant insights into the mechanisms governing stem cell migration, which may be applicable to other organisms, including mammals. The study highlights the role of inter-organ communication mediated by cytokines, specifically Upd2, in regulating the directional migration of stem cells. This concept of systemic signaling is also observed in mammals, where various cytokines and growth factors influence stem cell behavior. For instance, in mammals, the migration of hematopoietic stem cells is regulated by signals from the bone marrow microenvironment, including chemokines and cytokines such as SDF-1 (CXCL12) and IL-6, which are analogous to the Upd2 signaling pathway in Drosophila. Moreover, the study emphasizes the importance of planar cell polarity (PCP) in maintaining the disciplined migration of tracheal progenitors. PCP is a conserved mechanism in many organisms, including mammals, where it plays a crucial role in the orientation and movement of cells during development and tissue regeneration. Understanding how JAK/STAT signaling and PCP interact to regulate stem cell migration in Drosophila may inform similar pathways in mammals, potentially leading to novel therapeutic strategies for enhancing stem cell mobilization and tissue repair in regenerative medicine.

Q: What other signaling pathways or mechanisms, besides the JAK/STAT pathway and planar cell polarity, might be involved in coordinating the directional migration of stem cells in response to systemic cues?

In addition to the JAK/STAT pathway and planar cell polarity, several other signaling pathways and mechanisms are likely involved in coordinating the directional migration of stem cells in response to systemic cues. One prominent pathway is the Wnt signaling pathway, which is known to regulate cell migration and polarity through its effects on cytoskeletal dynamics and cell adhesion. Wnt signaling can influence the expression of various genes involved in cell motility and has been implicated in the migration of neural stem cells and other progenitor populations. Another critical pathway is the chemokine signaling pathway, which utilizes chemokines to create gradients that guide stem cell migration. For example, the interaction between chemokines and their receptors can direct the movement of hematopoietic stem cells towards sites of injury or inflammation. Additionally, the Notch signaling pathway plays a role in cell fate determination and can influence the migratory behavior of stem cells by modulating their interactions with the surrounding microenvironment. Integrin signaling is also essential for stem cell migration, as integrins mediate cell adhesion to the extracellular matrix (ECM) and facilitate the transduction of mechanical and biochemical signals that guide migration. Furthermore, the role of mechanical cues, such as tissue stiffness and topography, in influencing stem cell behavior is gaining recognition, suggesting that physical properties of the microenvironment can also coordinate directional migration.

Q: Could the vesicular trafficking system that transports the Upd2 cytokine from the fat body to the tracheal progenitors be targeted as a potential therapeutic approach to modulate stem cell behavior in regenerative medicine or disease contexts?

Yes, the vesicular trafficking system that transports the Upd2 cytokine from the fat body to the tracheal progenitors presents a promising target for therapeutic intervention in regenerative medicine and disease contexts. By modulating this vesicular transport mechanism, it may be possible to enhance or inhibit the signaling pathways that regulate stem cell migration and behavior. For instance, enhancing the efficiency of Upd2 transport could improve the recruitment and migration of stem cells to sites of injury, thereby promoting tissue regeneration. This could be particularly beneficial in conditions where stem cell mobilization is impaired, such as in aging or certain degenerative diseases. Pharmacological agents that stimulate vesicle formation or enhance the function of Rab GTPases involved in vesicular trafficking could be explored as potential therapies. Conversely, in contexts where excessive stem cell migration contributes to disease, such as in cancer metastasis, targeting the vesicular transport of Upd2 could provide a means to inhibit aberrant stem cell behavior. By disrupting the signaling pathways activated by Upd2, it may be possible to reduce the migratory capacity of cancer stem cells, thereby limiting tumor spread. Overall, targeting the vesicular trafficking system offers a novel approach to modulate stem cell behavior, with the potential for applications in both regenerative therapies and cancer treatment.

核心概念

Upd2, a cytokine produced by the Drosophila fat body, is essential for maintaining the disciplined, directional migration of tracheal stem cells through the activation of the JAK/STAT signaling pathway and the regulation of planar cell polarity genes.

摘要

The study investigates the mechanisms underlying the directional migration of tracheal stem cells (progenitors) in Drosophila. The key findings are:

The fat body, the functional analog of mammalian adipose tissue, is essential for maintaining the disciplined, anterior-to-posterior migration of tracheal progenitors. Disruption of the fat body leads to bidirectional, undisciplined movement of the progenitors.
The fat body-derived cytokine Upd2 targets the tracheal progenitors and activates the JAK/STAT signaling pathway in these cells. Knockdown of Upd2 or components of the JAK/STAT pathway (Dome, Hop, Stat92E) phenocopies the bidirectional migration observed upon fat body disruption.
JAK/STAT signaling in the tracheal progenitors promotes the expression of genes involved in planar cell polarity (PCP), such as Dachsous, Four-jointed, Frizzled, and Fat2. Disruption of these PCP components also leads to undisciplined progenitor migration.
Upd2 is transported from the fat body to the tracheal progenitors through a vesicular trafficking mechanism involving Rab5, Rab7, Grasp65, and the tetraspanin Lbm. Perturbation of this vesicular transport system impairs JAK/STAT signaling and the disciplined migration of progenitors.

In summary, the study uncovers an inter-organ communication mechanism involving the fat body-derived cytokine Upd2, which regulates the directional migration of tracheal stem cells through the activation of JAK/STAT signaling and the modulation of planar cell polarity.

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"The fat body resides anatomically in proximity with trachea and is the principal reservoir for energy consumption."
"Expression of hid and rpr in L3 stage impaired fat body integrity and adipocyte abundance, and generated slender larvae and pupae."
"Knockdown of upd2 in the fat body led to bidirectional movement of tracheal progenitors, reminiscent of fat body ablation."
"Depletion of components of the JAK/STAT pathway (Dome, Hop, Stat92E) in tracheal progenitors also caused bidirectional migration."
"Perturbation of planar cell polarity genes (Dachsous, Four-jointed, Frizzled, Fat2) in tracheal progenitors led to undisciplined migration."
"Upd2 is transported from the fat body to the tracheal progenitors through a vesicular trafficking mechanism involving Rab5, Rab7, Grasp65, and the tetraspanin Lbm."

引用

"The directional migration of the progenitors relies on JAK/STAT signaling and its downstream targets of planar cell polarity (PCP) components."
"Upd2, a cytokine produced by the fat body, is essential for maintaining the disciplined, directional migration of tracheal stem cells through the activation of the JAK/STAT signaling pathway and the regulation of planar cell polarity genes."
"The transport of Upd2 from fat body to trachea suggests intensive inter-organ communication during the migration of tracheal progenitors."

从中提取的关键见解

Fat body-derived cytokine Upd2 controls disciplined migration of tracheal stem cells in Drosophila

by Huang,H., Do... 在 www.biorxiv.org 07-05-2024

https://www.biorxiv.org/content/10.1101/2024.07.03.601877v2

更深入的查询

How might the findings from this study on Drosophila tracheal stem cells be applicable to the regulation of stem cell migration in other organisms, including mammals?

The findings from this study on Drosophila tracheal stem cells provide significant insights into the mechanisms governing stem cell migration, which may be applicable to other organisms, including mammals. The study highlights the role of inter-organ communication mediated by cytokines, specifically Upd2, in regulating the directional migration of stem cells. This concept of systemic signaling is also observed in mammals, where various cytokines and growth factors influence stem cell behavior. For instance, in mammals, the migration of hematopoietic stem cells is regulated by signals from the bone marrow microenvironment, including chemokines and cytokines such as SDF-1 (CXCL12) and IL-6, which are analogous to the Upd2 signaling pathway in Drosophila.
Moreover, the study emphasizes the importance of planar cell polarity (PCP) in maintaining the disciplined migration of tracheal progenitors. PCP is a conserved mechanism in many organisms, including mammals, where it plays a crucial role in the orientation and movement of cells during development and tissue regeneration. Understanding how JAK/STAT signaling and PCP interact to regulate stem cell migration in Drosophila may inform similar pathways in mammals, potentially leading to novel therapeutic strategies for enhancing stem cell mobilization and tissue repair in regenerative medicine.

What other signaling pathways or mechanisms, besides the JAK/STAT pathway and planar cell polarity, might be involved in coordinating the directional migration of stem cells in response to systemic cues?

In addition to the JAK/STAT pathway and planar cell polarity, several other signaling pathways and mechanisms are likely involved in coordinating the directional migration of stem cells in response to systemic cues. One prominent pathway is the Wnt signaling pathway, which is known to regulate cell migration and polarity through its effects on cytoskeletal dynamics and cell adhesion. Wnt signaling can influence the expression of various genes involved in cell motility and has been implicated in the migration of neural stem cells and other progenitor populations.
Another critical pathway is the chemokine signaling pathway, which utilizes chemokines to create gradients that guide stem cell migration. For example, the interaction between chemokines and their receptors can direct the movement of hematopoietic stem cells towards sites of injury or inflammation. Additionally, the Notch signaling pathway plays a role in cell fate determination and can influence the migratory behavior of stem cells by modulating their interactions with the surrounding microenvironment.
Integrin signaling is also essential for stem cell migration, as integrins mediate cell adhesion to the extracellular matrix (ECM) and facilitate the transduction of mechanical and biochemical signals that guide migration. Furthermore, the role of mechanical cues, such as tissue stiffness and topography, in influencing stem cell behavior is gaining recognition, suggesting that physical properties of the microenvironment can also coordinate directional migration.

Could the vesicular trafficking system that transports the Upd2 cytokine from the fat body to the tracheal progenitors be targeted as a potential therapeutic approach to modulate stem cell behavior in regenerative medicine or disease contexts?

Yes, the vesicular trafficking system that transports the Upd2 cytokine from the fat body to the tracheal progenitors presents a promising target for therapeutic intervention in regenerative medicine and disease contexts. By modulating this vesicular transport mechanism, it may be possible to enhance or inhibit the signaling pathways that regulate stem cell migration and behavior.
For instance, enhancing the efficiency of Upd2 transport could improve the recruitment and migration of stem cells to sites of injury, thereby promoting tissue regeneration. This could be particularly beneficial in conditions where stem cell mobilization is impaired, such as in aging or certain degenerative diseases. Pharmacological agents that stimulate vesicle formation or enhance the function of Rab GTPases involved in vesicular trafficking could be explored as potential therapies.
Conversely, in contexts where excessive stem cell migration contributes to disease, such as in cancer metastasis, targeting the vesicular transport of Upd2 could provide a means to inhibit aberrant stem cell behavior. By disrupting the signaling pathways activated by Upd2, it may be possible to reduce the migratory capacity of cancer stem cells, thereby limiting tumor spread.
Overall, targeting the vesicular trafficking system offers a novel approach to modulate stem cell behavior, with the potential for applications in both regenerative therapies and cancer treatment.