Abstract:
:We report that p73 is expressed in multiciliated cells (MCCs), is required for MCC differentiation, and directly regulates transcriptional modulators of multiciliogenesis. Loss of ciliary biogenesis provides a unifying mechanism for many phenotypes observed in p73 knockout mice including hydrocephalus; hippocampal dysgenesis; sterility; and chronic inflammation/infection of lung, middle ear, and sinus. Through p73 and p63 ChIP-seq using murine tracheal cells, we identified over 100 putative p73 target genes that regulate MCC differentiation and homeostasis. We validated Foxj1, a transcriptional regulator of multiciliogenesis, and many other cilia-associated genes as direct target genes of p73 and p63. We show p73 and p63 are co-expressed in a subset of basal cells and suggest that p73 marks these cells for MCC differentiation. In summary, p73 is essential for MCC differentiation, functions as a critical regulator of a transcriptome required for MCC differentiation, and, like p63, has an essential role in development of tissues.
journal_name
Cell Repjournal_title
Cell reportsauthors
Marshall CB,Mays DJ,Beeler JS,Rosenbluth JM,Boyd KL,Santos Guasch GL,Shaver TM,Tang LJ,Liu Q,Shyr Y,Venters BJ,Magnuson MA,Pietenpol JAdoi
10.1016/j.celrep.2016.02.035subject
Has Abstractpub_date
2016-03-15 00:00:00pages
2289-300issue
10issn
2211-1247pii
S2211-1247(16)30138-3journal_volume
14pub_type
杂志文章相关文献
Cell Reports文献大全abstract::Folates are cofactors for biosynthetic enzymes in all eukaryotic and prokaryotic cells. Animals cannot synthesize folate and must acquire it from their diet or microbiota. Previously, we showed that inhibiting E. coli folate synthesis increases C. elegans lifespan. Here, we show that restriction or supplementation of ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.01.051
更新日期:2016-02-23 00:00:00
abstract::Viral persistence specifically inhibits CD4 Th1 responses and promotes Tfh immunity, but the mechanisms that suppress Th1 cells and the disease consequences of their loss are unclear. Here, we demonstrate that the loss of CD4 Th1 cells specifically leads to progressive CD8 T cell decline and dysfunction during viral p...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.08.065
更新日期:2016-09-20 00:00:00
abstract::Senescence is a cellular response preventing tumorigenesis. The Ras oncogene is frequently activated or mutated in human cancers, but Ras activation is insufficient to transform primary cells. In a search for cooperating oncogenes, we identify the lysine demethylase JMJD2A/KDM4A. We show that JMJD2A functions as a neg...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2012.09.033
更新日期:2012-11-29 00:00:00
abstract::Amyloidosis is a major problem in over one hundred diseases, including Alzheimer's disease (AD). Using the iDISCO visualization method involving targeted molecular labeling, tissue clearing, and light-sheet microscopy, we studied plaque formation in the intact AD mouse brain at up to 27 months of age. We visualized am...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.06.060
更新日期:2016-07-26 00:00:00
abstract::Oligodendrogenesis occurs during early postnatal development, coincident with neurogenesis and synaptogenesis, raising the possibility that microglia-dependent pruning mechanisms that modulate neurons regulate myelin sheath formation. Here we show a population of ameboid microglia migrating from the ventricular zone i...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108047
更新日期:2020-08-18 00:00:00
abstract::Neuregulin-1 (NRG1) gene variants are associated with increased genetic risk for schizophrenia. It is unclear whether risk haplotypes cause elevated or decreased expression of NRG1 in the brains of schizophrenia patients, given that both findings have been reported from autopsy studies. To study NRG1 functions in vivo...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.07.026
更新日期:2014-08-21 00:00:00
abstract::Mutations in BLM helicase predispose Bloom syndrome (BS) patients to a wide spectrum of cancers. We demonstrate that MIB1-ubiquitylated BLM in G1 phase functions as an adaptor protein by enhancing the binding of transcription factor c-Jun and its E3 ligase, Fbw7α. BLM enhances the K48/K63-linked ubiquitylation on c-Ju...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.06.101
更新日期:2018-07-24 00:00:00
abstract::The role of neurotrophic factors as endogenous survival proteins for brain neurons remains contentious. In the cerebellum, the signals controlling survival of molecular layer interneurons (MLIs) are unknown, and direct evidence for the requirement of a full complement of MLIs for normal cerebellar function and motor l...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.05.030
更新日期:2017-06-06 00:00:00
abstract::In many organs, stem cell function depends on communication with their niche partners. Cranial sensory neurons develop in close proximity to blood vessels; however, whether vasculature is an integral component of their niches is yet unknown. Here, two separate roles for vasculature in cranial sensory neurogenesis in z...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.107903
更新日期:2020-07-14 00:00:00
abstract::Transfer RNA (tRNA) fragmentation in response to stress conditions has been described in many organisms. tRNA fragments have been found in association with small interfering RNA (siRNA) components, but the biological role of these interactions remains unclear. We report here that the tRNA methyltransferase Dnmt2 is es...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.07.046
更新日期:2013-09-12 00:00:00
abstract::Inflammasome activation is associated with numerous diseases. However, in vivo detection of the activated inflammasome complex has been limited by a dearth of tools. We have developed transgenic mice that ectopically express the fluorescent adaptor protein, apoptosis-associated speck-like protein containing a caspase ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.06.011
更新日期:2016-07-12 00:00:00
abstract::Experimental large-scale screens for drug repositioning are limited by restriction to in vitro conditions and lack of applicability to real human conditions. Here, we developed an in silico screen in human in vivo conditions using a reference of single gene mutations' non-tissue-specific "core transcriptome signatures...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.09.031
更新日期:2018-10-09 00:00:00
abstract::Previous efforts to identify cross-neutralizing antibodies to the receptor-binding site (RBS) of ebolavirus glycoproteins have been unsuccessful, largely because the RBS is occluded on the viral surface. We report a monoclonal antibody (FVM04) that targets a uniquely exposed epitope within the RBS; cross-neutralizes E...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.04.026
更新日期:2016-05-17 00:00:00
abstract::Current theories of muscle contraction propose that the power stroke of a myosin motor is the sole source of mechanical energy driving the sliding filaments of a contracting muscle. These models exclude titin, the largest protein in the human body, which determines the passive elasticity of muscles. Here, we show that...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.01.025
更新日期:2016-02-16 00:00:00
abstract::People tend to fall asleep when gently rocked or vibrated. Experimental studies have shown that rocking promotes sleep in humans and mice. However, the mechanisms underlying the phenomenon are not well understood. A habituation model proposes that habituation, a form of non-associative learning, mediates sleep inducti...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108462
更新日期:2020-12-01 00:00:00
abstract::Health and survival in old age can be improved by changes in gene expression. RNA polymerase (Pol) I is the essential, conserved enzyme whose task is to generate the pre-ribosomal RNA (rRNA). We find that reducing the levels of Pol I activity is sufficient to extend lifespan in the fruit fly. This effect can be recapi...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.01.017
更新日期:2020-02-11 00:00:00
abstract::Clinical transplantation of tissue fragments, including islets, faces a critical challenge because of a lack of effective strategies that ensure efficient engraftment through the timely integration of vascular networks. We recently developed a complex organoid engineering method by "self-condensation" culture based on...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.03.123
更新日期:2018-05-08 00:00:00
abstract::During chronic infection, the inflammatory cytokine interferon gamma (IFNγ) damages hematopoietic stem cells (HSCs) by disrupting quiescence and promoting excessive terminal differentiation. However, the mechanism by which IFNγ hinders HSC quiescence remains undefined. Using intravital 3-dimensional microscopy, we fin...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108530
更新日期:2020-12-22 00:00:00
abstract::Oxytocin and its receptor (Oxtr) play a crucial role in the postnatal transition of neuronal GABA neurotransmission from excitatory to inhibitory, a developmental process known as the GABA switch. Using hippocampal neurons from Oxtr-null mice, we show that (1) Oxtr is necessary for the correct timing of the GABA switc...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.03.013
更新日期:2016-04-05 00:00:00
abstract::Cell-cycle arrest in quiescence and senescence is largely orchestrated by the retinoblastoma (Rb) tumor-suppressor pathway, but the mechanisms underlying the quiescence-senescence switch remain unclear. Here, we show that the crosstalk between the Rb-AKT-signaling pathways forms this switch by controlling the overlapp...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.03.006
更新日期:2014-04-10 00:00:00
abstract::In the presynaptic terminal, the magnitude and location of Ca2+ entry through voltage-gated Ca2+ channels (VGCCs) regulate the efficacy of neurotransmitter release. However, how presynaptic active zone proteins control mammalian VGCC levels and organization is unclear. To address this, we deleted the CAST/ELKS protein...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.06.024
更新日期:2018-07-10 00:00:00
abstract::GABAergic synapses in brain circuits generate inhibitory output signals with submillisecond latency and temporal precision. Whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Here, we examined the Ca2+ sensor of exocytosis at GABAergic basket cell (BC) to Pu...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.12.067
更新日期:2017-01-17 00:00:00
abstract::The Fanconi anemia (FA) pathway repairs DNA interstrand crosslinks (ICLs). Many FA proteins are recruited to ICLs in a timely fashion so that coordinated repair can occur. However, the mechanism of this process is poorly understood. Here, we report the purification of a FANCD2-containing protein complex with multiple ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.107850
更新日期:2020-07-07 00:00:00
abstract::The transcriptional coactivators PGC-1α and PGC-1β are widely thought to be required for mitochondrial biogenesis and fiber typing in skeletal muscle. Here, we show that mice lacking both PGC-1s in myocytes do indeed have profoundly deficient mitochondrial respiration but, surprisingly, have preserved mitochondrial co...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.04.023
更新日期:2013-05-30 00:00:00
abstract::Replication of a damaged DNA template can threaten the integrity of the genome, requiring the use of various mechanisms to tolerate DNA lesions. The Smc5/6 complex, together with the Nse2/Mms21 SUMO ligase, plays essential roles in genome stability through undefined tasks at damaged replication forks. Various subunits...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.10.123
更新日期:2019-12-03 00:00:00
abstract::Astroglia regulate neurovascular coupling while engaging in signal exchange with neurons. The underlying cellular machinery is thought to rely on astrocytic Ca2+ signals, but what controls their amplitude and waveform is poorly understood. Here, we employ time-resolved two-photon excitation fluorescence imaging in acu...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.02.043
更新日期:2020-03-10 00:00:00
abstract::The MRE11-RAD50-NBS1 complex plays a central role in response to DNA double-strand breaks. Here, we identify a patient with bone marrow failure and developmental defects caused by biallelic RAD50 mutations. One of the mutations creates a null allele, whereas the other (RAD50E1035Δ) leads to the loss of a single residu...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.108559
更新日期:2020-12-29 00:00:00
abstract::Recent studies have shown that lysines can be posttranslationally modified by various types of acylations. However, except for acetylation, very little is known about their scope and cellular distribution. We mapped thousands of succinylation sites in bacteria (E. coli), yeast (S. cerevisiae), human (HeLa) cells, and ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.07.024
更新日期:2013-08-29 00:00:00
abstract::Recurrent epidemics of drug-resistant Staphylococcus aureus illustrate the rapid lapse of antibiotic efficacy following clinical implementation. Over the last decade, community-associated methicillin-resistant S. aureus (MRSA) has emerged as a dominant cause of infections, and this problem is amplified by the hyper-vi...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.03.018
更新日期:2019-04-02 00:00:00
abstract::The hair follicle (HF) is a complex miniorgan that serves as an ideal model system to study stem cell (SC) interactions with the niche during growth and regeneration. Dermal papilla (DP) cells are required for SC activation during the adult hair cycle, but signal exchange between niche and SC precursors/transit-amplif...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.02.078
更新日期:2016-03-29 00:00:00