Klinefelter syndrome(KS)is the most common sex chromosome disorder in men.It is characterized by germ cell loss and other variable clinical features,including autoimmunity.The sex-determining region of Y(SRY)-box 13(S...Klinefelter syndrome(KS)is the most common sex chromosome disorder in men.It is characterized by germ cell loss and other variable clinical features,including autoimmunity.The sex-determining region of Y(SRY)-box 13(Sox13)gene is expressed in mouse spermatogonia.In addition,it has been identified as islet cell autoantigen 12(ICA12),which is involved in the pathogenesis of autoimmune diseases,including type 1 diabetes mellitus(DM)and primary biliary cirrhosis.SOX13 expression has never been investigated in patients with KS.In this age-matched,case-control study performed on ten patients with KS and ten controls,we found that SOX13 is significantly downregulated in peripheral blood mononuclear cells of patients with KS compared to controls.This finding might be consistent with the germ cell loss typical of patients with KS.However,the role of SOX13 in the pathogenesis of germ cell loss and humoral autoimmunity in patients with KS deserves to be further explored.展开更多
Heterogeneous nuclear ribonucleoproteins（hn RNPs） belong to the RNA-binding proteins family. They are involved in processing heterogeneous nuclear RNAs（hn RNAs） into mature m RNAs. These proteins participate in ev...Heterogeneous nuclear ribonucleoproteins（hn RNPs） belong to the RNA-binding proteins family. They are involved in processing heterogeneous nuclear RNAs（hn RNAs） into mature m RNAs. These proteins participate in every step of m RNA cycle, such as m RNA export, localization, translation, stability and alternative splicing. At least 14 major hn RNPs, which have structural and functional homologues in mammals, are expressed in Drosophila melanogaster. Until now, six of these hn RNPs are known to be nucleus-localized and associated with the long non-coding RNA（lnc RNA） heat shock responsive u（hsru）in the omega speckle compartments（u-speckles）. The chromatin remodeler ISWI is the catalytic subunit of several ATP-dependent chromatin-remodeling complexes, and it is an essential factor for organization of u-speckles. Indeed, in ISWI null mutant, severe defects in u-speckles structure are detectable. Here, we clarify the role of ISWI in the hn RNPs-hsru interaction. Moreover, we describe how ISWI by its remodeling activity, controls hsru and hn RNPs engagement in u-speckles. Finally, we demonstrate that the sequestration of hn RNPs in u-speckles nuclear compartment is a fundamental event in gene expression control and represents a key step in the regulation of several pathways.展开更多
Understanding how certain animals are capable of regenerating their hearts will provide much needed insights into how this process can be induced in humans in order to reverse the damage caused by myocardial infarctio...Understanding how certain animals are capable of regenerating their hearts will provide much needed insights into how this process can be induced in humans in order to reverse the damage caused by myocardial infarction.Currently,it is becoming increasingly evident that cardiac interstitial cells play crucial roles during cardiac regeneration.To understand how interstitial cells behave during this process,we performed single-cell RNA sequencing of regenerating zebrafish hearts.Using a combination of immunohistochemistry,chemical inhibition,and novel transgenic animals,we were able to investigate the role of cell type-specific mechanisms during cardiac regeneration.This approach allowed us to identify a number of important regenerative processes within the interstitial cell populations.Here,we provide detailed insight into how interstitial cells behave during cardiac regeneration,which will serve to increase our understanding of how this process could eventually be induced in humans.展开更多
文摘Klinefelter syndrome(KS)is the most common sex chromosome disorder in men.It is characterized by germ cell loss and other variable clinical features,including autoimmunity.The sex-determining region of Y(SRY)-box 13(Sox13)gene is expressed in mouse spermatogonia.In addition,it has been identified as islet cell autoantigen 12(ICA12),which is involved in the pathogenesis of autoimmune diseases,including type 1 diabetes mellitus(DM)and primary biliary cirrhosis.SOX13 expression has never been investigated in patients with KS.In this age-matched,case-control study performed on ten patients with KS and ten controls,we found that SOX13 is significantly downregulated in peripheral blood mononuclear cells of patients with KS compared to controls.This finding might be consistent with the germ cell loss typical of patients with KS.However,the role of SOX13 in the pathogenesis of germ cell loss and humoral autoimmunity in patients with KS deserves to be further explored.
基金supported by an Associazione Italiana Ricerca sul Cancro (AIRC) (MFAG-12779) fellowshipsupported by My First Airc Grant (MFAG) number 12779 from AIRC to M.C.O
文摘Heterogeneous nuclear ribonucleoproteins（hn RNPs） belong to the RNA-binding proteins family. They are involved in processing heterogeneous nuclear RNAs（hn RNAs） into mature m RNAs. These proteins participate in every step of m RNA cycle, such as m RNA export, localization, translation, stability and alternative splicing. At least 14 major hn RNPs, which have structural and functional homologues in mammals, are expressed in Drosophila melanogaster. Until now, six of these hn RNPs are known to be nucleus-localized and associated with the long non-coding RNA（lnc RNA） heat shock responsive u（hsru）in the omega speckle compartments（u-speckles）. The chromatin remodeler ISWI is the catalytic subunit of several ATP-dependent chromatin-remodeling complexes, and it is an essential factor for organization of u-speckles. Indeed, in ISWI null mutant, severe defects in u-speckles structure are detectable. Here, we clarify the role of ISWI in the hn RNPs-hsru interaction. Moreover, we describe how ISWI by its remodeling activity, controls hsru and hn RNPs engagement in u-speckles. Finally, we demonstrate that the sequestration of hn RNPs in u-speckles nuclear compartment is a fundamental event in gene expression control and represents a key step in the regulation of several pathways.
基金MRI is supported by the French National Research Agency(ANR-10-INBS-04,‘Investments for the future')MGX acknowledges financial support from France Génomique National infrastrusture,funded as part of Investissement d‘Avenir’program managed by Agence National pour la Recherche(ANR-10-INBS-09)+2 种基金The Jopling lab is part of the Laboratory of Excellence lon Channel Science and Therapeutics supported by a grant from the ANRWork in the Jopling lab is supported by grants from the‘la Fondation Leducq'and from the ANR(ANR-20-CE14-003 MetabOx-Heart)A.H.was supported by European Research Area Network on Cardiovascular Diseases(ERA-CVD,ANR-18-ECVD-0006)awarded to T.M.-M.
文摘Understanding how certain animals are capable of regenerating their hearts will provide much needed insights into how this process can be induced in humans in order to reverse the damage caused by myocardial infarction.Currently,it is becoming increasingly evident that cardiac interstitial cells play crucial roles during cardiac regeneration.To understand how interstitial cells behave during this process,we performed single-cell RNA sequencing of regenerating zebrafish hearts.Using a combination of immunohistochemistry,chemical inhibition,and novel transgenic animals,we were able to investigate the role of cell type-specific mechanisms during cardiac regeneration.This approach allowed us to identify a number of important regenerative processes within the interstitial cell populations.Here,we provide detailed insight into how interstitial cells behave during cardiac regeneration,which will serve to increase our understanding of how this process could eventually be induced in humans.
