RNA Helicase DDX5 Inhibits Reprogramming to Pluripotency by miRNA-Based Repression of RYBP and its PRC1-Dependent and -Independent Functions.


:RNA-binding proteins (RBPs), in addition to their functions in cellular homeostasis, play important roles in lineage specification and maintaining cellular identity. Despite their diverse and essential functions, which touch on nearly all aspects of RNA metabolism, the roles of RBPs in somatic cell reprogramming are poorly understood. Here we show that the DEAD-box RBP DDX5 inhibits reprogramming by repressing the expression and function of the non-canonical polycomb complex 1 (PRC1) subunit RYBP. Disrupting Ddx5 expression improves the efficiency of iPSC generation and impedes processing of miR-125b, leading to Rybp upregulation and suppression of lineage-specific genes via RYBP-dependent ubiquitination of H2AK119. Furthermore, RYBP is required for PRC1-independent recruitment of OCT4 to the promoter of Kdm2b, a histone demethylase gene that promotes reprogramming by reactivating endogenous pluripotency genes. Together, these results reveal important functions of DDX5 in regulating reprogramming and highlight the importance of a Ddx5-miR125b-Rybp axis in controlling cell fate.


Cell Stem Cell


Cell stem cell


Li H,Lai P,Jia J,Song Y,Xia Q,Huang K,He N,Ping W,Chen J,Yang Z,Li J,Yao M,Dong X,Zhao J,Hou C,Esteban MA,Gao S,Pei D,Hutchins AP,Yao H




Has Abstract


2017-04-06 00:00:00














  • De Novo DNA Methylation: Marking the Path from Stem Cell to Neural Fate.

    abstract::DNA methylation is an epigenetic mark that plays pivotal roles in gene regulation, but its functions in neural fate decisions are poorly understood. In this issue of Cell Stem Cell, Ziller et al. (2018) show that the de novo methyltransferase Dnmt3a ensures efficient generation of motor neurons from stem cells. ...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Sawai A,Dasen JS

    更新日期:2018-04-05 00:00:00

  • Autoimmune T cells lured to a FASL web of death by MSCs.

    abstract::Achieving immune tolerance through cell transplantation is a promising approach for treating autoimmune disease. In this issue of Cell Stem Cell, Akiyama et al. (2012) demonstrate that human and mouse mesenchymal stem cells can induce immune suppression by attracting and killing autoreactive T cells, which stimulates ...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Murphy WJ,Nolta JA

    更新日期:2012-05-04 00:00:00

  • Engineering Hematopoietic Stem Cells: Lessons from Development.

    abstract::Cell engineering has brought us tantalizingly close to the goal of deriving patient-specific hematopoietic stem cells (HSCs). While directed differentiation and transcription factor-mediated conversion strategies have generated progenitor cells with multilineage potential, to date, therapy-grade engineered HSCs remain...

    journal_title:Cell stem cell

    pub_type: 杂志文章,评审


    authors: Rowe RG,Mandelbaum J,Zon LI,Daley GQ

    更新日期:2016-06-02 00:00:00

  • Capturing Totipotent Stem Cells.

    abstract::Minority subpopulations within embryonic stem cell cultures display an expanded developmental potential similar to that of early embryo blastomeres or the early inner cell mass. The ability to isolate and culture totipotent cells capable of giving rise to the entire conceptus would enhance our capacity to study early ...

    journal_title:Cell stem cell

    pub_type: 杂志文章,评审


    authors: Baker CL,Pera MF

    更新日期:2018-01-04 00:00:00

  • Close Quarters Can Be a Good Fit for Stem Cells to Become T Cells.

    abstract::Human pluripotent stem cells (PSCs) could potentially provide a potentially unlimited supply of T cells. In this issue of Cell Stem Cell, Montel-Hagen et al. (2019) take advantage of a three-dimensional mouse stromal cell-based system that combines mesoderm specification with organoid-induced hematopoietic differentia...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Trotman-Grant A,Zúñiga-Pflücker JC

    更新日期:2019-03-07 00:00:00

  • Putting Two Heads Together to Build a Better Brain.

    abstract::3D organoids enable in vitro human brain development models, but they have not yet recapitulated some essential features of brain circuit formation. Recently, several studies appearing in Nature, Nature Methods, and Cell Stem Cell generated fused organoid models of inhibitory and excitatory neuron development, which c...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Mich JK,Close JL,Levi BP

    更新日期:2017-09-07 00:00:00

  • mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging.

    abstract::Epidermal integrity is a complex process established during embryogenesis and maintained throughout the organism lifespan by epithelial stem cells. Although Wnt regulates normal epithelial stem cell renewal, aberrant Wnt signaling can contribute to cancerous growth. Here, we explored the consequences of persistent exp...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Castilho RM,Squarize CH,Chodosh LA,Williams BO,Gutkind JS

    更新日期:2009-09-04 00:00:00

  • Sowing the Seeds of Clonal Hematopoiesis.

    abstract::As humans age, hematopoietic stem cells (HSCs) occasionally acquire mutations in genes including DNMT3A that enable them to outcompete other HSCs and increase leukemia risk. In this issue of Cell Stem Cell, Tovy et al. (2020) report a previously uncharacterized mechanism by which DNMT3A loss confers increased fitness ...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Liggett LA,Voit RA,Sankaran VG

    更新日期:2020-08-06 00:00:00

  • Genome Editing in hPSCs Reveals GATA6 Haploinsufficiency and a Genetic Interaction with GATA4 in Human Pancreatic Development.

    abstract::Human disease phenotypes associated with haploinsufficient gene requirements are often not recapitulated well in animal models. Here, we have investigated the association between human GATA6 haploinsufficiency and a wide range of clinical phenotypes that include neonatal and adult-onset diabetes using CRISPR (clustere...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Shi ZD,Lee K,Yang D,Amin S,Verma N,Li QV,Zhu Z,Soh CL,Kumar R,Evans T,Chen S,Huangfu D

    更新日期:2017-05-04 00:00:00

  • Tetraspanin 3 Is Required for the Development and Propagation of Acute Myelogenous Leukemia.

    abstract::Acute Myelogenous Leukemia (AML) is an aggressive cancer that strikes both adults and children and is frequently resistant to therapy. Thus, identifying signals needed for AML propagation is a critical step toward developing new approaches for treating this disease. Here, we show that Tetraspanin 3 is a target of the ...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Kwon HY,Bajaj J,Ito T,Blevins A,Konuma T,Weeks J,Lytle NK,Koechlein CS,Rizzieri D,Chuah C,Oehler VG,Sasik R,Hardiman G,Reya T

    更新日期:2015-08-06 00:00:00

  • Correction of a genetic disease in mouse via use of CRISPR-Cas9.

    abstract::The CRISPR-Cas9 system has been employed to generate mutant alleles in a range of different organisms. However, so far there have not been reports of use of this system for efficient correction of a genetic disease. Here we show that mice with a dominant mutation in Crygc gene that causes cataracts could be rescued by...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Wu Y,Liang D,Wang Y,Bai M,Tang W,Bao S,Yan Z,Li D,Li J

    更新日期:2013-12-05 00:00:00

  • Eliminating Cancer Stem Cells in CML with Combination Transcriptional Therapy.

    abstract::Leukemia stem cells (LSCs) are resistant to current therapies used to treat chronic myeloid leukemia (CML). Abraham et al. (2016) have identified a molecular network critical for CML LSC survival and propose that simultaneously targeting two of their major transcriptional regulators, p53 and c-Myc, may facilitate thei...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Carvajal LA,Steidl U

    更新日期:2016-07-07 00:00:00

  • The Isl1/Ldb1 Complex Orchestrates Genome-wide Chromatin Organization to Instruct Differentiation of Multipotent Cardiac Progenitors.

    abstract::Cardiac stem/progenitor cells hold great potential for regenerative therapies; however, the mechanisms regulating their expansion and differentiation remain insufficiently defined. Here we show that Ldb1 is a central regulator of genome organization in cardiac progenitor cells, which is crucial for cardiac lineage dif...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Caputo L,Witzel HR,Kolovos P,Cheedipudi S,Looso M,Mylona A,van IJcken WF,Laugwitz KL,Evans SM,Braun T,Soler E,Grosveld F,Dobreva G

    更新日期:2015-09-03 00:00:00

  • Key endothelial signals required for hematopoietic recovery.

    abstract::In this issue of Cell Stem Cell, Hooper et al. (2009) use a combination of immunohistochemistry and flow cytometry to characterize the bone marrow vasculature both before and after injury. The authors demonstrate that recovery of normal hematopoiesis after myelosuppressive insult is dependent upon endothelial VEGFR2. ...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Porter RL,Calvi LM

    更新日期:2009-03-06 00:00:00

  • More than One Way to Skin a Wound.

    abstract::Large cutaneous and non-healing ulcers exhibit impaired epithelialization, which represents a major therapeutic challenge. Recently in Nature, Kurita et al. (2018) reported a surprising potential source of epithelial cells. The authors demonstrate that wound-resident mesenchymal cells can be reprogrammed to generate e...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Ankawa R,Fuchs Y

    更新日期:2018-11-01 00:00:00

  • Intestinal Enteroendocrine Lineage Cells Possess Homeostatic and Injury-Inducible Stem Cell Activity.

    abstract::Several cell populations have been reported to possess intestinal stem cell (ISC) activity during homeostasis and injury-induced regeneration. Here, we explored inter-relationships between putative mouse ISC populations by comparative RNA-sequencing (RNA-seq). The transcriptomes of multiple cycling ISC populations clo...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Yan KS,Gevaert O,Zheng GXY,Anchang B,Probert CS,Larkin KA,Davies PS,Cheng ZF,Kaddis JS,Han A,Roelf K,Calderon RI,Cynn E,Hu X,Mandleywala K,Wilhelmy J,Grimes SM,Corney DC,Boutet SC,Terry JM,Belgrader P,Ziraldo SB

    更新日期:2017-07-06 00:00:00

  • Age-related changes in niche cells influence hematopoietic stem cell function.

    abstract::In a recent issue of Nature, Mayack et al. (2010) use young and old parabiotic mice to show that systemic signals from the young parabiont rejuvenate hematopoietic stem cell function via the microenvironmental niche. ...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Oakley EJ,Van Zant G

    更新日期:2010-02-05 00:00:00

  • Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus.

    abstract::Production of new neurons in the adult hippocampus decreases with age; this decline may underlie age-related cognitive impairment. Here we show that continuous depletion of the neural stem cell pool, as a consequence of their division, may contribute to the age-related decrease in hippocampal neurogenesis. Our results...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Encinas JM,Michurina TV,Peunova N,Park JH,Tordo J,Peterson DA,Fishell G,Koulakov A,Enikolopov G

    更新日期:2011-05-06 00:00:00

  • Mesenchymal Niche-Specific Expression of Cxcl12 Controls Quiescence of Treatment-Resistant Leukemia Stem Cells.

    abstract::Chronic myeloid leukemia (CML) originates in a hematopoietic stem cell (HSC) transformed by the breakpoint cluster region (BCR)-abelson (ABL) oncogene and is effectively treated with tyrosine kinase inhibitors (TKIs). TKIs do not eliminate disease-propagating leukemic stem cells (LSCs), suggesting a deeper understandi...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Agarwal P,Isringhausen S,Li H,Paterson AJ,He J,Gomariz Á,Nagasawa T,Nombela-Arrieta C,Bhatia R

    更新日期:2019-05-02 00:00:00

  • Evaluation of Stuart et al.: Distinct Molecular Trajectories Converge to Induce Naive Pluripotency.

    abstract::An example of the peer review process for "Distinct molecular trajectories converge to induce naive pluripotency" (Stuart et al., 2019) is presented here. ...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Stadtfeld M

    更新日期:2019-09-05 00:00:00

  • Modeling a genetic risk for schizophrenia in iPSCs and mice reveals neural stem cell deficits associated with adherens junctions and polarity.

    abstract::Defects in brain development are believed to contribute toward the onset of neuropsychiatric disorders, but identifying specific underlying mechanisms has proven difficult. Here, we took a multifaceted approach to investigate why 15q11.2 copy number variants are prominent risk factors for schizophrenia and autism. Fir...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Yoon KJ,Nguyen HN,Ursini G,Zhang F,Kim NS,Wen Z,Makri G,Nauen D,Shin JH,Park Y,Chung R,Pekle E,Zhang C,Towe M,Hussaini SM,Lee Y,Rujescu D,St Clair D,Kleinman JE,Hyde TM,Krauss G,Christian KM,Rapoport JL,Wein

    更新日期:2014-07-03 00:00:00

  • 3D Modeling of Esophageal Development using Human PSC-Derived Basal Progenitors Reveals a Critical Role for Notch Signaling.

    abstract::Pluripotent stem cells (PSCs) could provide a powerful system to model development of the human esophagus, whose distinct tissue organization compared to rodent esophagus suggests that developmental mechanisms may not be conserved between species. We therefore established an efficient protocol for generating esophagea...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Zhang Y,Yang Y,Jiang M,Huang SX,Zhang W,Al Alam D,Danopoulos S,Mori M,Chen YW,Balasubramanian R,Chuva de Sousa Lopes SM,Serra C,Bialecka M,Kim E,Lin S,Toste de Carvalho ALR,Riccio PN,Cardoso WV,Zhang X,Snoeck HW,Q

    更新日期:2018-10-04 00:00:00

  • Spatially Restricted Stromal Wnt Signaling Restrains Prostate Epithelial Progenitor Growth through Direct and Indirect Mechanisms.

    abstract::Cell-autonomous Wnt signaling has well-characterized functions in controlling stem cell activity, including in the prostate. While niche cells secrete Wnt ligands, the effects of Wnt signaling in niche cells per se are less understood. Here, we show that stromal cells in the proximal prostatic duct near the urethra, a...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Wei X,Zhang L,Zhou Z,Kwon OJ,Zhang Y,Nguyen H,Dumpit R,True L,Nelson P,Dong B,Xue W,Birchmeier W,Taketo MM,Xu F,Creighton CJ,Ittmann MM,Xin L

    更新日期:2019-05-02 00:00:00

  • The emergence of hematopoietic stem cells is initiated in the placental vasculature in the absence of circulation.

    abstract::The mouse placenta was unveiled as an important reservoir for hematopoietic stem cells (HSCs), yet the origin of placental HSCs was unknown. By tracking developing HSCs by expression of Runx1-lacZ and CD41, we have found that HSCs emerge in large vessels in the placenta. Analysis of Ncx1(-/-) embryos, which lack a hea...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Rhodes KE,Gekas C,Wang Y,Lux CT,Francis CS,Chan DN,Conway S,Orkin SH,Yoder MC,Mikkola HK

    更新日期:2008-03-06 00:00:00

  • Single-Cell RNA-Seq Analysis Maps Development of Human Germline Cells and Gonadal Niche Interactions.

    abstract::Human fetal germ cells (FGCs) are precursors to sperm and eggs and are crucial for maintenance of the species. However, the developmental trajectories and heterogeneity of human FGCs remain largely unknown. Here we performed single-cell RNA-seq analysis of over 2,000 FGCs and their gonadal niche cells in female and ma...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Li L,Dong J,Yan L,Yong J,Liu X,Hu Y,Fan X,Wu X,Guo H,Wang X,Zhu X,Li R,Yan J,Wei Y,Zhao Y,Wang W,Ren Y,Yuan P,Yan Z,Hu B,Guo F,Wen L,Tang F,Qiao J

    更新日期:2017-06-01 00:00:00

  • Stem Cells Expand Insights into Human Brain Evolution.

    abstract::Substantial expansion in the number of cerebral cortex neurons is thought to underlie cognitive differences between humans and other primates, although the mechanisms underlying this expansion are unclear. Otani et al. (2016) utilize PSC-derived brain organoids to study how species-specific differences in cortical pro...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Dyer MA

    更新日期:2016-04-07 00:00:00

  • Metabolic makeover for HSCs.

    abstract::Hematopoietic stem cells (HSCs) must at times exit quiescence to divide and produce differentiated blood cells. In this issue of Cell Stem Cell, Takubo et al. (2013) and Yu et al. (2013) show that these opposing actions require distinct metabolic programs to meet the changing energy demands of self-renewing HSCs. ...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Warr MR,Passegué E

    更新日期:2013-01-03 00:00:00

  • Of Mice and Man: Differential DNMT Dependence in Mammalian ESCs.

    abstract::Liao et al. (2015) recently reported on the effects of disrupting DNA methyltransferase activity in human embryonic stem cells (hESCs). This work highlights key differences between mammalian ESC models upon the loss of these essential proteins and provides comprehensive base resolution methylome maps of DNMT targets d...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Bogdanović O,Lister R

    更新日期:2015-05-07 00:00:00

  • Adult neural stem cells bridge their niche.

    abstract::Major developments in the neural stem cell (NSC) field in recent years provide new insights into the nature of the NSC niche. In this perspective, we integrate recent anatomical data on the organization of the two main neurogenic niches in the adult brain, the ventricular-subventricular zone (V-SVZ) and the subgranula...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Fuentealba LC,Obernier K,Alvarez-Buylla A

    更新日期:2012-06-14 00:00:00

  • CIRM Alpha Stem Cell Clinics: Collaboratively Addressing Regenerative Medicine Challenges.

    abstract::The California Institute for Regenerative Medicine (CIRM) Alpha Stem Cell Clinic (ASCC) Network was launched in 2015 to address a compelling unmet medical need for rigorous, FDA-regulated, stem cell-related clinical trials for patients with challenging, incurable diseases. Here, we describe our multi-center experience...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Jamieson CHM,Millan MT,Creasey AA,Lomax G,Donohoe ME,Walters MC,Abedi M,Bota DA,Zaia JA,Adams JS

    更新日期:2018-06-01 00:00:00