ISWI ATPase Smarca5 Regulates Differentiation of Thymocytes Undergoing beta-Selection

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F19%3A00518837" target="_blank" >RIV/68378041:_____/19:00518837 - isvavai.cz</a>

Alternative codes found

RIV/68378050:_____/19:00518837

Result on the web

<a href="https://www.jimmunol.org/content/202/12/3434" target="_blank" >https://www.jimmunol.org/content/202/12/3434</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.4049/jimmunol.1801684" target="_blank" >10.4049/jimmunol.1801684</a>

Result language

angličtina

Original language name

ISWI ATPase Smarca5 Regulates Differentiation of Thymocytes Undergoing beta-Selection

Original language description

Development of lymphoid progenitors requires a coordinated regulation of gene expression, DNA replication, and gene rearrangement. Chromatin-remodeling activities directed by SWI/SNF2 superfamily complexes play important roles in these processes. In this study, we used a conditional knockout mouse model to investigate the role of Smarca5, a member of the ISWI subfamily of such complexes, in early lymphocyte development. Smarca5 deficiency results in a developmental block at the DN3 stage of alpha beta thymocytes and pro-B stage of early B cells at which the rearrangement of Ag receptor loci occurs. It also disturbs the development of committed (CD73(+)) gamma delta thymocytes. The alpha beta thymocyte block is accompanied by massive apoptotic depletion of beta-selected double-negative DN3 cells and premitotic arrest of CD4/CD8 double-positive cells. Although Smarca5-deficient alpha beta T cell precursors that survived apoptosis were able to undergo a successful TCR beta rearrangement, they exhibited a highly abnormal mRNA profile, including the persistent expression of CD44 and CD25 markers characteristic of immature cells. We also observed that the p53 pathway became activated in these cells and that a deficiency of p53 partially rescued the defect in thymus cellularity (in contrast to early B cells) of Smarca5-deficient mice. However, the activation of p53 was not primarily responsible for the thymocyte developmental defects observed in the Smarca5 mutants. Our results indicate that Smarca5 plays a key role in the development of thymocytes undergoing beta-selection, gamma delta thymocytes, and also B cell progenitors by regulating the transcription of early differentiation programs.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30101 - Human genetics

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Immunology

ISSN

0022-1767

e-ISSN

—

Volume of the periodical

202

Issue of the periodical within the volume

12

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

3434-3446

UT code for WoS article

000470083000010

EID of the result in the Scopus database

2-s2.0-85067217780