Spatial, a gene expressed in thymic stromal cells, depends on three-dimensional thymus organization for its expression

Flomerfelt, FA; Kim, MG; Schwartz, R H

doi:10.1038/sj.gene.6363695

Cited by 13 publications

(26 citation statements)

References 24 publications

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“…2C). Since computational analyses predict an homology to homeobox and POU domain transcription factors [13], we first suggested a nuclear function of Spatial specific to mature mTEC. In order to see if all mature mTEC are also Spatial positive, we quantified on WT adult thymic sections the respective cellularity of Aire 1 and Spatial 1 cells presents in medullary areas, detected with K5 or MTS10 markers (Fig.…”

Section: Spatial Is Expressed In Mature Medullary Thymic Epithelial Cmentioning

confidence: 99%

“…In the thymus, Spatial expression was first documented by Flomerfelt et al [13]. Accordingly, it has been described that in mouse embryos, Spatial-g expression begins at day 10 while Spatial-a is not detected until day 12.…”

Section: Introductionmentioning

confidence: 96%

“…1) and seems to be involved in cell differentiation in other organs [10,11]. In addition, computational analyses predict a homology to homeobox and POU domain transcription factors [13]. Therefore, we can suggest that its expression could be related to the medulla organization through an Aire-dependant manner.…”

mentioning

confidence: 94%

“…According to the highly specific distribution of Spatial in cellular extensions, we determined its association to the kinesin motor KIF17 conserved in the flagellum and dendrites [10,11]. These previous findings thus imply a function of Spatial in cell differentiation in a microtubule-dependent mechanism.In the thymus, Spatial expression was first documented by Flomerfelt et al [13]. Accordingly, it has been described that in mouse embryos, Spatial-g expression begins at day 10 while Spatial-a is not detected until day 12.…”

mentioning

confidence: 96%

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Spatial (Tbata) expression in mature medullary thymic epithelial cells

et al. 2010

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The Spatial gene is expressed in highly polarized cell types such as testis germ cells, brain neurons and thymic epithelial cells (TEC). Its expression was documented in testis and brain but poorly characterized in thymus. Here, we characterize for the first time Spatial-expressing TEC throughout ontogeny and adult mouse thymus. Spatial is expressed in thymicfated domain by embryonic day E10.5 and persists in subcapsular, cortical, medullary epithelial cells and in MTS24 1 progenitor TEC. Using mouse strains in which thymocyte development is blocked at various stages, we show that Spatial expression is independent of thymocyte-derived signals during thymus organogenesis. Analyses on purified thymic cell subsets show that Spatial short isoforms are expressed in cortical TEC (cTEC) and mature medullary TEC (mTEC). Spatial long isoforms were detected in the same TEC population. Spatial presents a nuclear distribution specific to mature mTEC expressing UEA1 and Aire. Aire-and RANKL-deficient mice revealed that Spatial expression is drastically reduced in the thymus of these mutants. These findings reveal a critical function of Aire in regulating Spatial expression, which is compatible with promiscuous Spatial gene expression. 530 IntroductionThe vertebrate thymus is responsible for the production of functional nonautoreactive T lymphocytes. In this primary lymphoid organ, T-cell precursors commonly called thymocytes undergo a series of developmental stages through interactions with thymic stromal cells, resulting in the generation of mature T lymphocytes that are exported to the periphery [1,2]. The unique function of the thymus resides mainly in the thymic epithelium, which forms the major subcompartment of the stroma [3,4]. The thymic epithelium itself is commonly divided into two main regions, the cortex and the medulla, and each of these regions contains several ultrastructurally and phenotypically distinct types of thymic epithelial cells (TEC) [5,6]. TEC are required both for thymus organogenesis and for the promotion of most if not all stages of thymocyte maturation [3,4]. Understanding the molecular mechanisms regulating TEC differentiation and function provides crucial insights into mechanisms controlling T-cell development in the thymus.Using DNA chip technology we isolated the Spatial gene (Stromal Protein Associated with Thymii and Lymph node), also known as Tbata (thymus, brain and testes associated), by an approach based on differential screening between different knock-out mice models exhibiting distinct thymic immunodeficiencies [7]. This analysis led to the identification of three adult variants of the Spatial gene expressed in the thymus [8]. In addition, we also described two other isoforms isolated in the testis [8][9][10]. According to the size of alternative spliced variants, we have respectively named Spatial isoforms: Spatial-a (1035 bp), Spatial-b (1002 bp), Spatial-g (933 bp) for the short isoforms identified in the thymus; Spatial-d (1353 bp) and Spatial-e (1454 bp) for the long isoforms ...

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Section: Spatial Is Expressed In Mature Medullary Thymic Epithelial Cmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

mentioning

confidence: 94%

mentioning

confidence: 96%

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Spatial (Tbata) expression in mature medullary thymic epithelial cells

et al. 2010

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“…This analysis led to the identification of three adult variants of the Spatial gene expressed in the thymus (GenBank accession nos. AF257502, AF257503 and AY243457) [2,3]. In addition, we also described two other isoforms isolated in the testis (GenBank accession no.…”

Section: Introductionmentioning

confidence: 98%

Neuronal distribution of Spatial in the developing cerebellum and hippocampus and its somatodendritic association with the kinesin motor KIF17

Irla

Saade

Fernandez

et al. 2007

Experimental Cell Research

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Recapitulation of Thymic Function by Tissue Engineering Strategies

Silva

Reis

Martins

et al. 2021

Adv Healthcare Materials

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The thymus is responsible for the development and selection of T lymphocytes, which in turn also participate in the maturation of thymic epithelial cells. These events occur through the close interactions between hematopoietic stem cells and developing thymocytes with the thymic stromal cells within an intricate 3D network. The complex thymic microenvironment and function, and the current therapies to induce thymic regeneration or to overcome the lack of a functional thymus are herein reviewed. The recapitulation of the thymic function using tissue engineering strategies has been explored as a way to control the body's tolerance to external grafts and to generate ex vivo T cells for transplantation. In this review, the main advances in the thymus tissue engineering field are disclosed, including both scaffold-and cell-based strategies. In light of the current gaps and limitations of the developed systems, the design of novel biomaterials for this purpose with unique features is also discussed.

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Spatial, a gene expressed in thymic stromal cells, depends on three-dimensional thymus organization for its expression

Cited by 13 publications

References 24 publications

Spatial (Tbata) expression in mature medullary thymic epithelial cells

Spatial (Tbata) expression in mature medullary thymic epithelial cells

Neuronal distribution of Spatial in the developing cerebellum and hippocampus and its somatodendritic association with the kinesin motor KIF17

Recapitulation of Thymic Function by Tissue Engineering Strategies

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