scholarly journals Analysis of LRRC45 indicates cooperative functions of distal appendages at early steps of ciliogenesis

2017 ◽  
Author(s):  
Bahtiyar Kurtulmus ◽  
Cheng Yuan ◽  
Jakob Schuy ◽  
Annett Neuner ◽  
Shoji Hata ◽  
...  
Keyword(s):  
Stem Cells ◽  
Basal Body ◽  
Tissue Homeostasis ◽  
The Core ◽  
Cilia Formation ◽  
Mother Centriole ◽  
Appendage Formation ◽  
Motile Cilia

AbstractCilia perform essential signalling functions during development and tissue homeostasis. Ciliary malfunction causes a variety of diseases, named ciliopathies. The key role that the mother centriole plays in cilia formation can be attributed to appendage proteins that associate exclusively with the mother centriole. The distal appendages form a platform that docks early ciliary vesicles and removes CP110/Cep97 inhibitory complexes from the mother centriole. Here, we analysed the role played by LRRC45 in appendage formation and ciliogenesis. We show that the core appendage proteins Cep83 and SCLT1 recruit LRRC45 to the mother centriole. Once there LRRC45 recruits FBF1. The association of LRRC45 with the basal body of primary and motile cilia in differentiated and stem cells reveals a broad function in ciliogenesis. In contrast to the appendage components Cep164 and Cep123, LRRC45 was neither essential for docking of early ciliary vesicles nor for removal of CP110. Rather, LRRC45 promotes cilia biogenesis in CP110-uncapped centrioles by organising centriolar satellites and promoting the docking of Rab8 GTPase-positive vesicles. We propose that, instead of acting solely as a platform to recruit early vesicles, centriole appendages form discrete scaffolds of cooperating proteins that execute specific functions that promote the initial steps of ciliogenesis.

scholarly journals The microtubule affinity regulating kinase MARK4 promotes axoneme extension during early ciliogenesis

2013 ◽  
Vol 200 (4) ◽  
pp. 505-522 ◽  
Author(s):  
Stefanie Kuhns ◽  
Kerstin N. Schmidt ◽  
Jürgen Reymann ◽  
Daniel F. Gilbert ◽  
Annett Neuner ◽  
...  
Keyword(s):  
Rna Interference ◽  
Protein Kinases ◽  
Basal Body ◽  
Kinase Activity ◽  
Complete Removal ◽  
Cilia Formation ◽  
Mother Centriole ◽  
Functional Analyses ◽  
Novel Protein

Despite the critical contributions of cilia to embryonic development and human health, key regulators of cilia formation await identification. In this paper, a functional RNA interference–based screen linked 30 novel protein kinases with ciliogenesis. Of them, we have studied the role of the microtubule (MT)-associated protein/MT affinity regulating kinase 4 (MARK4) in depth. MARK4 associated with the basal body and ciliary axoneme in human and murine cell lines. Ultrastructural and functional analyses established that MARK4 kinase activity was required for initiation of axoneme extension. We identified the mother centriolar protein ODF2 as an interaction partner of MARK4 and showed that ODF2 localization to the centriole partially depended on MARK4. Our data indicated that, upon MARK4 or ODF2 knockdown, the ciliary program arrested before the complete removal of the CP110–Cep97 inhibitory complex from the mother centriole, suggesting that these proteins act at this level of axonemal extension. We propose that MARK4 is a critical positive regulator of early steps in ciliogenesis.

scholarly journals Cep164 mediates vesicular docking to the mother centriole during early steps of ciliogenesis

2012 ◽  
Vol 199 (7) ◽  
pp. 1083-1101 ◽  
Author(s):  
Kerstin N. Schmidt ◽  
Stefanie Kuhns ◽  
Annett Neuner ◽  
Birgit Hub ◽  
Hanswalter Zentgraf ◽  
...  
Keyword(s):  
Basal Body ◽  
Distal Part ◽  
Membrane Biogenesis ◽  
Step Process ◽  
Ciliary Membrane ◽  
Functional Assays ◽  
Apical Domain ◽  
Cilia Formation ◽  
Mother Centriole

Cilia formation is a multi-step process that starts with the docking of a vesicle at the distal part of the mother centriole. This step marks the conversion of the mother centriole into the basal body, from which axonemal microtubules extend to form the ciliary compartment. How vesicles are stably attached to the mother centriole to initiate ciliary membrane biogenesis is unknown. Here, we investigate the molecular role of the mother centriolar component Cep164 in ciliogenesis. We show that Cep164 was indispensable for the docking of vesicles at the mother centriole. Using biochemical and functional assays, we identified the components of the vesicular transport machinery, the GEF Rabin8 and the GTPase Rab8, as interacting partners of Cep164. We propose that Cep164 is targeted to the apical domain of the mother centriole to provide the molecular link between the mother centriole and the membrane biogenesis machinery that initiates cilia formation.

scholarly journals Tcf3 is an integral component of the core regulatory circuitry of embryonic stem cells

2008 ◽  
Vol 22 (6) ◽  
pp. 746-755 ◽  
Author(s):  
M. F. Cole ◽  
S. E. Johnstone ◽  
J. J. Newman ◽  
M. H. Kagey ◽  
R. A. Young
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
The Core ◽  
Integral Component

scholarly journals Apoptosis resistance of senescent cells is an intrinsic barrier for senolysis induced by cardiac glycosides

2021 ◽  
Author(s):  
Pavel I. Deryabin ◽  
Alla N. Shatrova ◽  
Aleksandra V. Borodkina
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Broad Spectrum ◽  
General Feature ◽  
Cardiac Glycosides ◽  
Human Mesenchymal Stem Cells ◽  
Apoptosis Resistance ◽  
The Core ◽  
Bioinformatic Approaches

AbstractTargeted elimination of senescent cells, senolysis, is one of the core trends in the anti-aging therapy. Cardiac glycosides were recently proved to be a broad-spectrum senolytics. Here we tested senolytic properties of cardiac glycosides towards human mesenchymal stem cells (hMSCs). Cardiac glycosides had no senolytic ability towards senescent hMSCs of various origins. Using biological and bioinformatic approaches we compared senescence development in ‘cardiac glycosides-sensitive’ A549 and ‘-insensitive’ hMSCs. The absence of senolysis was found to be mediated by the effective potassium import and increased apoptosis resistance in senescent hMSCs. Weakening “antiapoptotic defense” predisposes hMSCs to senolysis. We revealed that apoptosis resistance, previously recognized as a common characteristic of senescence, in fact, is not a general feature of senescent cells. Moreover, only apoptosis-prone senescent cells are sensitive to cardiac glycosides-induced senolysis. Thus, we can speculate that the effectiveness of senolysis might depend on whether senescent cells indeed become apoptosis-resistant as compared to their proliferating counterparts. Graphic abstract

scholarly journals Growth Factors & Stem Cells Entrapment in Bio Compatible & Biodegradable Nano Particles to Prevent Early Degradation & Facilitate Gradual Release

2021 ◽  
Author(s):  
ANURUDDHA A. H. M. P. ◽  
C. A. N. FERNANDO ◽  
YOSHIHISA SAIDA ◽  
MINORU SAKURABA
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Extraction Process ◽  
Nano Particles ◽  
The Core ◽  
Experimental Process ◽  
One Step ◽  
Treatment Procedures ◽  
Early Degradation ◽  
Gradual Release

Abstract The use of growth factors and stem cells as the core treating agents is one step into creating a biocompatible Solid Lipid Nano Particles (SLNP) for treatments. Apart from obtaining these growth factors and stem cells from the patients, using the bi-product of the extraction process which is the lipid of the patient for the production of the SLNP assures the final product to be biocompatible and of a unique structure. The use of autologous cells and proteins from the patients makes the entire process medically ethical and more viable for treatment procedures. This article, thus discusses on the experimental process of developing such SLNP and the introduction of the relevant medical contraption designed uniquely for the procedure inclusive of a specified membrane.

Advanced platelet-rich fibrin extract treatment promotes the proliferation and differentiation of Human Adipose-Derived Mesenchymal Stem Cells through activation of tryptophan metabolism

2021 ◽  
Vol 16 ◽  
Author(s):  
Guan-Ming Lu ◽  
Li-Yuan Jiang ◽  
Dong-Lin Huang ◽  
Yong-Xian Rong ◽  
Yang-Hong Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Regulatory Network ◽  
Expression Profiles ◽  
Differential Expression Analysis ◽  
Tryptophan Metabolism ◽  
Enzyme Linked Immunosorbent Assay ◽  
Platelet Rich Fibrin ◽  
The Core ◽  
Proliferation And Differentiation

Background: Advanced platelet-rich fibrin extract (APRFE) contains a high concentration of various cytokines that are helpful for improving stem cells repair function. Objective: However, the underlying mechanism of APRFE improving stem cell repairing is not clear. Methods: We produced APRFE by centrifuging fresh peripheral blood samples and isolated and identified human adipose-derived mesenchymal stem cells (ADMSCs). The abundance of cytokines contained in APRFE was detected by the Enzyme-linked immunosorbent assay (ELISA). The ADMSCs treated with or without APRFE were collected for transcriptome sequencing. Results: Based on the sequencing data, the expression profiles were contracted. The differentially expressed genes and lncRNA (DEGs and DElncRNAs) were obtained using for the differential expression analysis. The lncRNA-miRNA-mRNA network was constructed based on the miRNet database. The further enrichment analysis results showed that the biological functions were mainly related to proliferation, differentiation, and cell-cell function. To explore the role of APRFE, the protein-protein interaction network was constructed among the cytokines included in APRFE and DEGs. Furthermore, we constructed the global regulatory network based on the RNAInter and TRRUST database. The pathways in the global regulatory network were considered as the core pathways. We found that the DEGs in the core pathways were associated with stemness scores. Conclusion: In summary, we predicted that APRFE activated three pathways (tryptophan metabolism, mTOR signaling pathway, and adipocytokine signaling) to promote the proliferation and differentiation of ADMSCs. The finding may be helpful for guiding the application of ADMSCs in the clinic.

Ultrastructure of the organ of Bellonci in the hypogean isopod Stenasellus virei boui Magniez (Crustacea, Asellota)

1992 ◽  
Vol 70 (1) ◽  
pp. 129-135
Author(s):  
Adriana Pitzalis ◽  
Christian Juberthie
Keyword(s):  
Glial Cells ◽  
Basal Body ◽  
Spatial Arrangement ◽  
Central Core ◽  
Sensory Cells ◽  
The Core ◽  
Ultrastructural Morphology

The ultrastructure of the organ of Bellonci in the hypogean isopod Stenasellus virei boui was investigated. There are two organs located anterodorsally, one on each side of the cephalon. Each organ consists of a wall surrounding a cavity with a central core irregular in shape. The bordering wall contains some glial cells and the inner dendritic segments of 25–28 sensory cells, each one bearing two cilia. Each cilium has a typical 9 + 0 axoneme, a basal body, and a long straight ciliary root that is at a right angle to the basal body; the cilium branches out into tubules that usually contain 1 microtubule, occasionally 2 or more. The ciliary tubules are gathered in three or four long bundles and are not linked to the core. The ciliary connections appear to be both conical and cylindrical. The ultrastructural morphology (polarization of the cilia, spatial arrangement of the bundles and central core) suggests that this organ can record directional stimuli.

scholarly journals Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem Cells

Cell ◽  
2008 ◽  
Vol 133 (6) ◽  
pp. 1106-1117 ◽  
Author(s):  
Xi Chen ◽  
Han Xu ◽  
Ping Yuan ◽  
Fang Fang ◽  
Mikael Huss ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Signaling Pathways ◽  
Embryonic Stem ◽  
Transcriptional Network ◽  
The Core

scholarly journals The Regulation of the CNS Innate Immune Response Is Vital for the Restoration of Tissue Homeostasis (Repair) after Acute Brain Injury: A Brief Review

2010 ◽  
Vol 2010 ◽  
pp. 1-18 ◽  
Author(s):  
M. R. Griffiths ◽  
P. Gasque ◽  
J. W. Neal
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
T Cell ◽  
Innate Immune Response ◽  
T Cell Activation ◽  
Cell Activation ◽  
Tissue Homeostasis ◽  
Innate Immune ◽  
Apoptotic Cells ◽  
Treg Population

Neurons and glia respond to acute injury by participating in the CNS innate immune response. This involves the recognition and clearance of “not self ” pathogens and “altered self ” apoptotic cells. Phagocytic receptors (CD14, CD36, TLR–4) clear “not self” pathogens; neurons and glia express “death signals” to initiate apoptosis in T cells.The complement opsonins C1q, C3, and iC3b facilitate the clearance of apoptotic cells by interacting with CR3 and CR4 receptors. Apoptotic cells are also cleared by the scavenger receptors CD14, Prs-R, TREM expressed by glia. Serpins also expressed by glia counter the neurotoxic effects of thrombin and other systemic proteins that gain entry to the CNS following injury. Complement pathway and T cell activation are both regulated by complement regulatory proteins expressed by glia and neurons. CD200 and CD47 are NIRegs expressed by neurons as “don't eat me” signals and they inhibit microglial activity preventing host cell attack. Neural stem cells regulate T cell activation, increase the Treg population, and suppress proinflammatory cytokine expression. Stem cells also interact with the chemoattractants C3a, C5a, SDF-1, and thrombin to promote stem cell migration into damaged tissue to support tissue homeostasis.

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