Trans-omics Impact of Thymoproteasome in Cortical Thymic Epithelial Cells

Ohigashi, Izumi; Tanaka, Yu; Kondo, Kenta; Fujimori, Sayumi; Kondo, Hiroyuki; Palin, Amy; Hoffmann, Victoria; Kozai, Mina; Matsushita, Yosuke; Uda, Shinsuke; Motosugi, Ryo; Hamazaki, Jun; Konishi, Hiroyuki; Murata, Shigeo; Tanaka, Keiji; Katagiri, Toyomasa; Kosako, Hidetaka; Takahama, Yousuke

doi:10.1016/j.celrep.2019.10.079

Cited by 34 publications

(100 citation statements)

References 55 publications

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“…Although TEC were found at ∼100-times greater frequency, the thymus from these mice had a normal structure, and supported a normal program of T cell development. Mass spectrometry proteomics and single cell RNA sequencing confirmed cTEC specific expression of Cathepsin L, TSPP, and β5t, and mTECspecific expression of Cathepsin S, CD40, and Aire (24). These mice could prove to be a useful platform for further interrogation of the cTEC compartment.…”

Section: Lineage Specific Thymic Epithelial Cells Ctec and Ctec Hetermentioning

confidence: 73%

“…In relation to functional heterogeneity within cTEC, thymic nurse cells (TNC) are large epithelial cell complexes in which single cTECs encase viable thymocytes. This is a unique feature of cTEC, and ∼10-15% of cTEC form such complexes; each containing between four and eight DP thymocytes (24). TNC are absent from the embryonic thymus, and are only detectable from 5 days post-birth; perhaps a reflection of a bias toward mature cTEC rather than cTEC-like progenitors.…”

Section: Lineage Specific Thymic Epithelial Cells Ctec and Ctec Hetermentioning

confidence: 96%

“…Interestingly, thymocytes contained within TNC are enriched for those that have undergone secondary TCRα rearrangements, suggesting they may provide an environment then enables efficient positive selection. The presence of such epithelial-thymocyte complexes results in an estimated 20% of RNA isolated from total cTECs reflecting gene expression by enclosed DP thymocytes (24). This can be seen in single cell RNA sequencing of cTECs where newborn and adult cTECs appear to be contaminated with DP thymocytes (26).…”

Section: Lineage Specific Thymic Epithelial Cells Ctec and Ctec Hetermentioning

confidence: 99%

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Generation and Regeneration of Thymic Epithelial Cells

2020

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The thymus is unique in its ability to support the maturation of phenotypically and functionally distinct T cell sub-lineages. Through its combined production of MHC-restricted conventional CD4 + and CD8 + , and Foxp3 + regulatory T cells, as well as non-conventional CD1d-restricted iNKT cells and invariant γδT cells, the thymus represents an important orchestrator of immune system development and control. It is now clear that thymus function is largely determined by the availability of stromal microenvironments. These specialized areas emerge during thymus organogenesis and are maintained throughout life. They are formed from both epithelial and mesenchymal components, and collectively they support a stepwise program of thymocyte development. Of these stromal cells, cortical, and medullary thymic epithelial cells represent functional components of thymic microenvironments in both the cortex and medulla. Importantly, a key feature of thymus function is that levels of T cell production are not constant throughout life. Here, multiple physiological factors including aging, stress and pregnancy can have either short-or long-term detrimental impact on rates of thymus function. Here, we summarize our current understanding of the development and function of thymic epithelial cells, and relate this to strategies to protect and/or restore thymic epithelial cell function for therapeutic benefit.

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Section: Lineage Specific Thymic Epithelial Cells Ctec and Ctec Hetermentioning

confidence: 73%

Section: Lineage Specific Thymic Epithelial Cells Ctec and Ctec Hetermentioning

confidence: 96%

Section: Lineage Specific Thymic Epithelial Cells Ctec and Ctec Hetermentioning

confidence: 99%

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Generation and Regeneration of Thymic Epithelial Cells

2020

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“…This continued Myc expression in TECs conferred expression of a fetal-specific transcriptional program, including high levels of expression of genes involved in cell cycle and ribosomal biogenesis (51). Interestingly, this ribosomal signature was unique to the Myc model, as another transgenic large thymus model, driven by cell cycle gene cyclin D1, did not present with increased transcripts of genes involved ribosomal biogenesis (51,67).…”

Section: Tecs Mediate Changes To Thymic Size Throughout Lifementioning

confidence: 97%

Postnatal Involution and Counter-Involution of the Thymus

et al. 2020

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Thymus involution occurs in all vertebrates. It is thought to impact on immune responses in the aged, and in other clinical circumstances such as bone marrow transplantation. Determinants of thymus growth and size are beginning to be identified. Ectopic expression of factors like cyclin D1 and Myc in thymic epithelial cells (TEC)s results in considerable increase in thymus size. These models provide useful experimental tools that allow thymus function to be understood. In future, understanding TEC-specific controllers of growth will provide new approaches to thymus regeneration.

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“…Recently, trans-omics, which combines the knowledge of signal transduction mechanisms, and database of omics analysis with systems biology, have been successful (Ohigashi et al, 2019;Yugi et al, 2016). However, these omics approaches presuppose that a cell population behaves uniformly.…”

Section: Introductionmentioning

confidence: 99%

Five patterns of cell signaling pathways associated with cell behavior

Takeda

Kawano

et al. 2020

Preprint

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Cell signaling pathway is complex systems. Here, we present a concept for a new approach to analyze cell signaling pathway associated with cell behavior. In theoretically, cell behavior is recognized by energy and fluctuation. In this study, we measured phosphorylation level of signal transducers in a cell and fluctuation of the phosphorylation level in the cell population using flow cytometry. Flow cytometric data of mean fluorescence intensity (MFI) and coefficient variation (CV) were considered to the energy and the fluctuation, respectively. Topologically, the changes of MFI and CV were categorized into five patterns (we tentatively named as attractive, subsequent, passive, counter, and negative arbiter). In this study, we clarified the relationship between the cell behavior and the five patterns. Furthermore, combining the five patterns can define the signaling pathways, such as simple activated signal, oscillating signal, regulatory signal, robust signal, or homeostatic signal. These observations provide a proof of concept for general strategy to use the five patterns for connection between cell signaling pathway and cell behavior.

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Trans-omics Impact of Thymoproteasome in Cortical Thymic Epithelial Cells

Cited by 34 publications

References 55 publications

Generation and Regeneration of Thymic Epithelial Cells

Generation and Regeneration of Thymic Epithelial Cells

Postnatal Involution and Counter-Involution of the Thymus

Five patterns of cell signaling pathways associated with cell behavior

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