Rockefeller University

About: Rockefeller University is a education organization based out in New York, New York, United States. It is known for research contribution in the topics: Population & Gene. The organization has 15867 authors who have published 32938 publications receiving 2940261 citations. The organization is also known as: Rockefeller University & Rockefeller Institute.

Functional annotation of a full-length mouse cDNA collection

Abstract: The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.

The origin and development of nonlymphoid tissue CD103+ DCs

Abstract: CD103+ dendritic cells (DCs) in nonlymphoid tissues are specialized in the cross-presentation of cell-associated antigens. However, little is known about the mechanisms that regulate the development of these cells. We show that two populations of CD11c+MHCII+ cells separated on the basis of CD103 and CD11b expression coexist in most nonlymphoid tissues with the exception of the lamina propria. CD103+ DCs are related to lymphoid organ CD8+ DCs in that they are derived exclusively from pre-DCs under the control of fms-like tyrosine kinase 3 (Flt3) ligand, inhibitor of DNA protein 2 (Id2), and IFN regulatory protein 8 (IRF8). In contrast, lamina propria CD103+ DCs express CD11b and develop independently of Id2 and IRF8. The other population of CD11c+MHCII+ cells in tissues, which is CD103−CD11b+, is heterogenous and depends on both Flt3 and MCSF-R. Our results reveal that nonlymphoid tissue CD103+ DCs and lymphoid organ CD8+ DCs derive from the same precursor and follow a related differentiation program.

ABA induction of miR159 controls transcript levels of two MYB factors during Arabidopsis seed germination.

Abstract: Upon seed imbibition, abscisic acid (ABA) levels decrease to allow embryos to germinate and develop into seedlings. However, under abiotic stress conditions, ABA levels remain high, and growth and development are arrested. Several transcription factors, including abscisic acid-insensitive (ABI)3 and ABI5, are known to control this developmental checkpoint. Here, we show that, in germinating Arabidopsis thaliana seeds, ABA induces the accumulation of microRNA 159 (miR159) in an ABI3-dependent fashion, and miRNA159 mediates cleavage of MYB101 and MYB33 transcripts in vitro and in vivo. The two MYB transcription factors function as positive regulators of ABA responses, as null mutants of myb33 and myb101 show hyposensitivity to the hormone. Consistent with this, miR159 over-expression suppresses MYB33 and MYB101 transcript levels and renders plants hyposensitive to ABA, whereas transgenic plants over-expressing cleavage-resistant forms of MYB33 and MYB101 are hypersensitive, as are plants over-expressing the Turnip mosaic virus (TuMV) P1/HC-Pro viral protein that is known to inhibit miRNA function. Our results suggest that ABA-induced accumulation of miR159 is a homeostatic mechanism to direct MYB33 and MYB101 transcript degradation to desensitize hormone signaling during seedling stress responses.

Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis

Abstract: Chronic mucocutaneous candidiasis disease (CMCD) may be caused by autosomal dominant (AD) IL-17F deficiency or autosomal recessive (AR) IL-17RA deficiency. Here, using whole-exome sequencing, we identified heterozygous germline mutations in STAT1 in 47 patients from 20 kindreds with AD CMCD. Previously described heterozygous STAT1 mutant alleles are loss-of-function and cause AD predisposition to mycobacterial disease caused by impaired STAT1-dependent cellular responses to IFN-γ. Other loss-of-function STAT1 alleles cause AR predisposition to intracellular bacterial and viral diseases, caused by impaired STAT1-dependent responses to IFN-α/β, IFN-γ, IFN-λ, and IL-27. In contrast, the 12 AD CMCD-inducing STAT1 mutant alleles described here are gain-of-function and increase STAT1-dependent cellular responses to these cytokines, and to cytokines that predominantly activate STAT3, such as IL-6 and IL-21. All of these mutations affect the coiled-coil domain and impair the nuclear dephosphorylation of activated STAT1, accounting for their gain-of-function and dominance. Stronger cellular responses to the STAT1-dependent IL-17 inhibitors IFN-α/β, IFN-γ, and IL-27, and stronger STAT1 activation in response to the STAT3-dependent IL-17 inducers IL-6 and IL-21, hinder the development of T cells producing IL-17A, IL-17F, and IL-22. Gain-of-function STAT1 alleles therefore cause AD CMCD by impairing IL-17 immunity.