The adrenal glands, located above the kidneys, are neuroendocrine organs that regulate numerous physiological processes. Structurally, the adrenal gland is divided into two distinct regions differing for developmental origins and functional roles: the outer cortex and the inner medulla. Contrary to its embryonic development, the postnatal adrenal medulla remains a poorly characterised tissue. The adrenal medulla plays a pivotal role in the body’s acute stress response, often referred to as the "fight or flight" mechanism. Other than chromaffin cells and neurons, a third cell type populates the medulla: sustentacular cells, whose supportive role still has to be properly characterised. Maintaining a stable population of catecholamine-secreting chromaffin cells is critical for lifelong physiological homeostasis. Currently, no stem/progenitor cell population has been identified in this postnatal tissue. Additionally, progenitor cells could be susceptible to oncogenic transformations, resulting in tumors such as neuroblastoma (NB), pheochromocytoma (PCC), and paraganglioma (PPGL). Recent studies have provided insight into sustentacular cells and their potential role as progenitor cells. These cells exhibited expression of glial markers similarly to embryonic Schwann Cell Precursors (SCPs) involved in sympathoadrenal system development. Notably, SOX2, a transcription factor associated with pluripotency, self-renewal, and plasticity, is co-expressed with SOX10 in SCPs during embryonic development. This research aims to provide a more detailed understanding of the postnatal adrenal medulla. In vivo genetic lineage tracing highlighted postnatal SOX10-expressing glial cells’ potential to differentiate into new TH+ chromaffin cells. IHC staining of postnatal mouse and human tissue revealed that SOX2 expression persists into adulthood, colocalizing in the nuclei of SOX10-expressing glial cells. A minor subset of these cells also expressed PHOX2B, a transcription factor involved in early sympathoadrenal specification, indicating a transitional state towards differentiation. SOX2+ SOX10+ PHOX2B+ triple- positive transitioning cells have been detected in a case of pheochromocytoma with an SDHB mutation and 1p loss. Here, sustentacular cells retained SDHB expression, suggesting they were not neoplastic. Nevertheless, the role of sustentacular cells in PPGL tumorigenesis should not be dismissed. Other than contributing to tumorigenesis in a cell-autonomous manner through commitment to differentiation, sustentacular cells may support tumor proliferation through paracrine signaling, as has been observed in other neuroendocrine organs such as the pituitary gland.
The adrenal glands, located above the kidneys, are neuroendocrine organs that regulate numerous physiological processes. Structurally, the adrenal gland is divided into two distinct regions differing for developmental origins and functional roles: the outer cortex and the inner medulla. Contrary to its embryonic development, the postnatal adrenal medulla remains a poorly characterised tissue. The adrenal medulla plays a pivotal role in the body’s acute stress response, often referred to as the "fight or flight" mechanism. Other than chromaffin cells and neurons, a third cell type populates the medulla: sustentacular cells, whose supportive role still has to be properly characterised. Maintaining a stable population of catecholamine-secreting chromaffin cells is critical for lifelong physiological homeostasis. Currently, no stem/progenitor cell population has been identified in this postnatal tissue. Additionally, progenitor cells could be susceptible to oncogenic transformations, resulting in tumors such as neuroblastoma (NB), pheochromocytoma (PCC), and paraganglioma (PPGL). Recent studies have provided insight into sustentacular cells and their potential role as progenitor cells. These cells exhibited expression of glial markers similarly to embryonic Schwann Cell Precursors (SCPs) involved in sympathoadrenal system development. Notably, SOX2, a transcription factor associated with pluripotency, self-renewal, and plasticity, is co-expressed with SOX10 in SCPs during embryonic development. This research aims to provide a more detailed understanding of the postnatal adrenal medulla. In vivo genetic lineage tracing highlighted postnatal SOX10-expressing glial cells’ potential to differentiate into new TH+ chromaffin cells. IHC staining of postnatal mouse and human tissue revealed that SOX2 expression persists into adulthood, colocalizing in the nuclei of SOX10-expressing glial cells. A minor subset of these cells also expressed PHOX2B, a transcription factor involved in early sympathoadrenal specification, indicating a transitional state towards differentiation. SOX2+ SOX10+ PHOX2B+ triple- positive transitioning cells have been detected in a case of pheochromocytoma with an SDHB mutation and 1p loss. Here, sustentacular cells retained SDHB expression, suggesting they were not neoplastic. Nevertheless, the role of sustentacular cells in PPGL tumorigenesis should not be dismissed. Other than contributing to tumorigenesis in a cell-autonomous manner through commitment to differentiation, sustentacular cells may support tumor proliferation through paracrine signaling, as has been observed in other neuroendocrine organs such as the pituitary gland.
Identification of postnatal adrenomedullary progenitor cells and their contribution in mediating intratumoral plasticity in human paraganglioma
SANTANGELI, CHRISTIAN
2023/2024
Abstract
The adrenal glands, located above the kidneys, are neuroendocrine organs that regulate numerous physiological processes. Structurally, the adrenal gland is divided into two distinct regions differing for developmental origins and functional roles: the outer cortex and the inner medulla. Contrary to its embryonic development, the postnatal adrenal medulla remains a poorly characterised tissue. The adrenal medulla plays a pivotal role in the body’s acute stress response, often referred to as the "fight or flight" mechanism. Other than chromaffin cells and neurons, a third cell type populates the medulla: sustentacular cells, whose supportive role still has to be properly characterised. Maintaining a stable population of catecholamine-secreting chromaffin cells is critical for lifelong physiological homeostasis. Currently, no stem/progenitor cell population has been identified in this postnatal tissue. Additionally, progenitor cells could be susceptible to oncogenic transformations, resulting in tumors such as neuroblastoma (NB), pheochromocytoma (PCC), and paraganglioma (PPGL). Recent studies have provided insight into sustentacular cells and their potential role as progenitor cells. These cells exhibited expression of glial markers similarly to embryonic Schwann Cell Precursors (SCPs) involved in sympathoadrenal system development. Notably, SOX2, a transcription factor associated with pluripotency, self-renewal, and plasticity, is co-expressed with SOX10 in SCPs during embryonic development. This research aims to provide a more detailed understanding of the postnatal adrenal medulla. In vivo genetic lineage tracing highlighted postnatal SOX10-expressing glial cells’ potential to differentiate into new TH+ chromaffin cells. IHC staining of postnatal mouse and human tissue revealed that SOX2 expression persists into adulthood, colocalizing in the nuclei of SOX10-expressing glial cells. A minor subset of these cells also expressed PHOX2B, a transcription factor involved in early sympathoadrenal specification, indicating a transitional state towards differentiation. SOX2+ SOX10+ PHOX2B+ triple- positive transitioning cells have been detected in a case of pheochromocytoma with an SDHB mutation and 1p loss. Here, sustentacular cells retained SDHB expression, suggesting they were not neoplastic. Nevertheless, the role of sustentacular cells in PPGL tumorigenesis should not be dismissed. Other than contributing to tumorigenesis in a cell-autonomous manner through commitment to differentiation, sustentacular cells may support tumor proliferation through paracrine signaling, as has been observed in other neuroendocrine organs such as the pituitary gland.File | Dimensione | Formato | |
---|---|---|---|
Santangeli_Christian.pdf
accesso riservato
Dimensione
7.98 MB
Formato
Adobe PDF
|
7.98 MB | Adobe PDF |
The text of this website © Università degli studi di Padova. Full Text are published under a non-exclusive license. Metadata are under a CC0 License
https://hdl.handle.net/20.500.12608/80841