scholarly journals FBW7 couples structural integrity with functional output of primary cilia

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Eleni Petsouki ◽  
Vasileios Gerakopoulos ◽  
Nicholas Szeto ◽  
Wenhan Chang ◽  
Mary Beth Humphrey ◽  
...  
Keyword(s):  
Stem Cell ◽  
Primary Cilia ◽  
Structural Integrity ◽  
Interaction Network ◽  
Stem Cell Differentiation ◽  
Bone Architecture ◽  
Structural Defects ◽  
Independent Manner ◽  
And Function ◽  
Msc Differentiation

AbstractStructural defects in primary cilia have robust effects in diverse tissues and systems. However, how disorders of ciliary length lead to functional outcomes are unknown. We examined the functional role of a ciliary length control mechanism of FBW7-mediated destruction of NDE1, in mesenchymal stem cell (MSC) differentiation. We show that FBW7 functions as a master regulator of both negative (NDE1) and positive (TALPID3) regulators of ciliogenesis, with an overall positive net effect on primary cilia formation, MSC differentiation to osteoblasts, and bone architecture. Deletion of Fbxw7 suppresses ciliation, Hedgehog activity, and differentiation, which are partially rescued in Fbxw7/Nde1-null cells. We also show that NDE1, despite suppressing ciliogenesis, promotes MSC differentiation by increasing the activity of the Hedgehog pathway by direct binding and enhancing GLI2 activity in a cilia-independent manner. We propose that FBW7 controls a protein-protein interaction network coupling ciliary structure and function, which is essential for stem cell differentiation.

scholarly journals FBW7 couples structural integrity with functional output of primary cilia

2020 ◽  
Author(s):  
Eleni Petsouki ◽  
Vasileios Gerakopoulos ◽  
Nicholas Szeto ◽  
Wenhan Chang ◽  
Mary Beth Humphrey ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Structural Integrity ◽  
Stem Cell Differentiation ◽  
Bone Architecture ◽  
Structural Defects ◽  
Independent Manner ◽  
Mesenchymal Stem Cell Differentiation ◽  
Cilia Formation ◽  
Length Changes ◽  
Msc Differentiation

AbstractStructural defects in cilia have robust effects in diverse tissues and systems. However, how ciliary length changes influence signaling output are unknown. Here, we examined the functional role of a ciliary length control mechanism whereby FBW7-mediated destruction of NDE1 positively regulated ciliary length, in mesenchymal stem cell differentiation. We show that FBW7 functions as a master regulator of both negative (NDE1) and positive (TALPID3) regulators of ciliogenesis, with an overall positive net effect on cilia formation, MSC differentiation, and bone architecture. Deletion of Fbxw7 suppresses ciliation, Hedgehog activity, and differentiation, which are rescued in Fbxw7/Nde1-null cells. However, despite formation of abnormally long cilia in Nde1-null cells, MSC differentiation is suppressed. NDE1 promotes MSC differentiation by increasing the activity of the Hedgehog pathway by direct binding and enhancing GLI2 activity in a cilia-independent manner. We propose that ciliary structure-function coupling is determined by intricate interactions of structural and functional proteins.

scholarly journals Plasmonic Nanofactors as Switchable Devices to Promote or Inhibit Neuronal Activity and Function

Nanomaterials ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 1029 ◽  
Author(s):  
Karrer M. Alghazali ◽  
Rabab N. Hamzah ◽  
Zeid A. Nima ◽  
Richard Steiner ◽  
Madhu Dhar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Neuronal Activity ◽  
Tissue Regeneration ◽  
Cellular Proliferation ◽  
Neuronal Cells ◽  
Stem Cell Differentiation ◽  
Extracellular Matrices ◽  
Specific Cancer ◽  
Cancer Cell Targeting ◽  
And Function

Gold nanosystems have been investigated extensively for a variety of applications, from specific cancer cell targeting to tissue regeneration. Specifically, a recent and exciting focus has been the gold nanosystems’ interface with neuronal biology. Researchers are investigating the ability to use these systems neuronal applications ranging from the enhancement of stem cell differentiation and therapy to stimulation or inhibition of neuronal activity. Most of these new areas of research are based on the integration of the plasmonic properties of such nanosystems into complex synthetic extracellular matrices (ECM) that can interact and affect positively the activity of neuronal cells. Therefore, the ability to integrate the plasmonic properties of these nanoparticles into multidimensional and morphological structures to support cellular proliferation and activity is potentially of great interest, particularly to address medical conditions that are currently not fully treatable. This review discusses some of the promising developments and unique capabilities offered by the integration of plasmonic nanosystems into morphologically complex ECM devices, designed to control and study the activity of neuronal cells.

scholarly journals Expression Patterns and Function of Chromatin Protein HMGB2 during Mesenchymal Stem Cell Differentiation

2011 ◽  
Vol 286 (48) ◽  
pp. 41489-41498 ◽  
Author(s):  
Noboru Taniguchi ◽  
Beatriz Caramés ◽  
Emily Hsu ◽  
Stephanie Cherqui ◽  
Yasuhiko Kawakami ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Mesenchymal Stem Cell ◽  
Expression Patterns ◽  
Stem Cell Differentiation ◽  
Chromatin Protein ◽  
Mesenchymal Stem Cell Differentiation ◽  
And Function

Could Substrate Stiffness and Oxygen Tension Regulate Stem Cell Differentiation During Fracture Healing?

2011 ◽  
Author(s):  
D. Burke ◽  
D. J. Kelly
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Fracture Healing ◽  
Oxygen Tension ◽  
Temporal Patterns ◽  
Stem Cell Differentiation ◽  
Tissue Differentiation ◽  
Substrate Stiffness ◽  
Spatial And Temporal Patterns ◽  
Msc Differentiation

Extrinsic mechanical signals have been implicated as key regulators of Mesenchymal Stem Cell (MSC) differentiation [1]. It has been possible to test different hypotheses for mechano-regulated differentiation by attempting to simulate regenerative events such as bone fracture repair [2]. During such events, repeatable spatial and temporal patterns of tissue differentiation occur. More recently, in vitro studies have identified other environmental cues, such as substrate stiffness [3] and oxygen tension [4], as key regulators of MSC differentiation. The hypothesis of this study is that a computational model that assumes substrate stiffness and oxygen tension regulate stem cell differentiation can be used to predict the spatial and temporal patterns of tissue differentiation that occur during fracture healing.

scholarly journals Primary Cilium Is Involved in Stem Cell Differentiation and Renewal through the Regulation of Multiple Signaling Pathways

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1428
Author(s):  
Sila Yanardag ◽  
Elena N. Pugacheva
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Signaling Pathways ◽  
Primary Cilium ◽  
Primary Cilia ◽  
Vision Loss ◽  
Stem Cell Differentiation ◽  
Future Research ◽  
Renal Anomalies

Signaling networks guide stem cells during their lineage specification and terminal differentiation. Primary cilium, an antenna-like protrusion, directly or indirectly plays a significant role in this guidance. All stem cells characterized so far have primary cilia. They serve as entry- or check-points for various signaling events by controlling the signal transduction and stability. Thus, defects in the primary cilia formation or dynamics cause developmental and health problems, including but not limited to obesity, cardiovascular and renal anomalies, hearing and vision loss, and even cancers. In this review, we focus on the recent findings of how primary cilium controls various signaling pathways during stem cell differentiation and identify potential gaps in the field for future research.

Bio-mimicking Shear Stress Environments for Enhancing Mesenchymal Stem Cell Differentiation

2020 ◽  
Vol 15 (5) ◽  
pp. 414-427
Author(s):  
Seep Arora ◽  
Akshaya Srinivasan ◽  
Chak Ming Leung ◽  
Yi-Chin Toh
Keyword(s):  
Stem Cells ◽  
Shear Stress ◽  
Stem Cell ◽  
Stem Cell Differentiation ◽  
In Vitro Differentiation ◽  
Msc Differentiation ◽  
Biophysical Cues

Mesenchymal stem cells (MSCs) are multipotent stromal cells, with the ability to differentiate into mesodermal (e.g., adipocyte, chondrocyte, hematopoietic, myocyte, osteoblast), ectodermal (e.g., epithelial, neural) and endodermal (e.g., hepatocyte, islet cell) lineages based on the type of induction cues provided. As compared to embryonic stem cells, MSCs hold a multitude of advantages from a clinical translation perspective, including ease of isolation, low immunogenicity and limited ethical concerns. Therefore, MSCs are a promising stem cell source for different regenerative medicine applications. The in vitro differentiation of MSCs into different lineages relies on effective mimicking of the in vivo milieu, including both biochemical and mechanical stimuli. As compared to other biophysical cues, such as substrate stiffness and topography, the role of fluid shear stress (SS) in regulating MSC differentiation has been investigated to a lesser extent although the role of interstitial fluid and vascular flow in regulating the normal physiology of bone, muscle and cardiovascular tissues is well-known. This review aims to summarise the current state-of-the-art regarding the role of SS in the differentiation of MSCs into osteogenic, cardiovascular, chondrogenic, adipogenic and neurogenic lineages. We will also highlight and discuss the potential of employing SS to augment the differentiation of MSCs to other lineages, where SS is known to play a role physiologically but has not yet been successfully harnessed for in vitro differentiation, including liver, kidney and corneal tissue lineage cells. The incorporation of SS, in combination with biochemical and biophysical cues during MSC differentiation, may provide a promising avenue to improve the functionality of the differentiated cells by more closely mimicking the in vivo milieu.

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