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


: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 differentiation and heart development. We demonstrate that Ldb1 binds to the key regulator of cardiac progenitors, Isl1, and protects it from degradation. Furthermore, the Isl1/Ldb1 complex promotes long-range enhancer-promoter interactions at the loci of the core cardiac transcription factors Mef2c and Hand2. Chromosome conformation capture followed by sequencing identified specific Ldb1-mediated interactions of the Isl1/Ldb1 responsive Mef2c anterior heart field enhancer with genes that play key roles in cardiac progenitor cell function and cardiovascular development. Importantly, the expression of these genes was downregulated upon Ldb1 depletion and Isl1/Ldb1 haplodeficiency. In conclusion, the Isl1/Ldb1 complex orchestrates a network for heart-specific transcriptional regulation and coordination in three-dimensional space during cardiogenesis.


Cell Stem Cell


Cell stem cell


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




Has Abstract


2015-09-03 00:00:00














  • Zika Virus NS4A and NS4B Proteins Deregulate Akt-mTOR Signaling in Human Fetal Neural Stem Cells to Inhibit Neurogenesis and Induce Autophagy.

    abstract::The current widespread outbreak of Zika virus (ZIKV) infection has been linked to severe clinical birth defects, particularly microcephaly, warranting urgent study of the molecular mechanisms underlying ZIKV pathogenesis. Akt-mTOR signaling is one of the key cellular pathways essential for brain development and autoph...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Liang Q,Luo Z,Zeng J,Chen W,Foo SS,Lee SA,Ge J,Wang S,Goldman SA,Zlokovic BV,Zhao Z,Jung JU

    更新日期:2016-11-03 00:00:00

  • Out of Many, One: Computational Reconstruction of Mouse Skin using Single-Cell Transcriptomics.

    abstract::Mammalian skin is a complex and heterogeneous tissue with several distinct compartments and stem cell populations. Joost et al. (2016) now use single-cell RNaseq to comprehensively reconstruct this complexity, revealing spatial and pseudotemporal differences between transcriptional programs in distinct compartments an...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Chen JC,Christiano AM

    更新日期:2016-10-06 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

  • Ch-ch-changes: hormones link stem cell differentiation with metabolic flux.

    abstract::Emerging evidence strongly suggests that stem cells and their differentiated progeny display distinct metabolic profiles, but how metabolic changes are coupled with organogenesis has remained unclear. Homem et al. (2014) now reveal a hormone-dependent pathway that couples metabolic changes with stem cell differentiati...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Buttitta L,Lee CY

    更新日期:2014-09-04 00:00:00

  • CHD7 in charge of neurogenesis.

    abstract::In this issue of Cell Stem Cell, Feng et al. (2013) report that the gene mutated in human CHARGE syndrome, ATP-dependent chromatin remodeling factor CHD7, contributes to the control of neurogenesis. The authors also report that exercise ameliorates these defects and suggest it as an intervention worthy of study in CHA...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Kim KH,Roberts CW

    更新日期:2013-07-03 00:00:00

  • GFAP Mutations in Astrocytes Impair Oligodendrocyte Progenitor Proliferation and Myelination in an hiPSC Model of Alexander Disease.

    abstract::Alexander disease (AxD) is a leukodystrophy that primarily affects astrocytes and is caused by mutations in the astrocytic filament gene GFAP. While astrocytes are thought to have important roles in controlling myelination, AxD animal models do not recapitulate critical myelination phenotypes and it is therefore not c...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Li L,Tian E,Chen X,Chao J,Klein J,Qu Q,Sun G,Sun G,Huang Y,Warden CD,Ye P,Feng L,Li X,Cui Q,Sultan A,Douvaras P,Fossati V,Sanjana NE,Riggs AD,Shi Y

    更新日期:2018-08-02 00:00:00

  • Neurofibromatosis-1 regulates neuronal and glial cell differentiation from neuroglial progenitors in vivo by both cAMP- and Ras-dependent mechanisms.

    abstract::Individuals with neurofibromatosis type 1 (NF1) develop abnormalities of both neuronal and glial cell lineages, suggesting that the NF1 protein neurofibromin is an essential regulator of neuroglial progenitor function. In this regard, Nf1-deficient embryonic telencephalic neurospheres exhibit increased self-renewal an...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Hegedus B,Dasgupta B,Shin JE,Emnett RJ,Hart-Mahon EK,Elghazi L,Bernal-Mizrachi E,Gutmann DH

    更新日期:2007-10-11 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

  • Stem cells by the sea.

    abstract::The 2009 ISSCR Annual Meeting in Barcelona will draw stem cell scientists from around the world to Europe, to connect to each other and to the local community. With record abstract submissions, we are sure to have an exciting meeting. ...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: McKay RD

    更新日期:2009-06-05 00:00:00

  • A precarious balance: pluripotency factors as lineage specifiers.

    abstract::Understanding the basis of the unrestricted multilineage differentiation potential of pluripotent cells will be of developmental and translational consequence. We propose that pluripotency transcription factors are lineage specifiers that direct commitment to specific fetal lineages. Individual factors bestow the abil...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Loh KM,Lim B

    更新日期:2011-04-08 00:00:00

  • Single-Cell Transcriptomics Meets Lineage Tracing.

    abstract::Reconstructing lineage relationships between cells within a tissue or organism is a long-standing aim in biology. Traditionally, lineage tracing has been achieved through the (genetic) labeling of a cell followed by the tracking of its offspring. Currently, lineage trajectories can also be predicted using single-cell ...

    journal_title:Cell stem cell

    pub_type: 杂志文章,评审


    authors: Kester L,van Oudenaarden A

    更新日期:2018-08-02 00:00:00

  • A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening.

    abstract::Gastric cancer displays marked molecular heterogeneity with aggressive behavior and treatment resistance. Therefore, good in vitro models that encompass unique subtypes are urgently needed for precision medicine development. Here, we have established a primary gastric cancer organoid (GCO) biobank that comprises norma...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Yan HHN,Siu HC,Law S,Ho SL,Yue SSK,Tsui WY,Chan D,Chan AS,Ma S,Lam KO,Bartfeld S,Man AHY,Lee BCH,Chan ASY,Wong JWH,Cheng PSW,Chan AKW,Zhang J,Shi J,Fan X,Kwong DLW,Mak TW,Yuen ST,Clevers H,Leung SY

    更新日期:2018-12-06 00:00:00

  • Illuminating the Properties of Prostate Luminal Progenitors.

    abstract::The identification of tumor-initiating cells represents a significant challenge for studies of prostate cancer. In a recent issue of Cell Reports, Agarwal and colleagues use organoid culture to ascertain two distinct luminal progenitors in a mouse model of prostate cancer, shedding new light on lineage relationships i...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Shen MM

    更新日期:2015-12-03 00:00:00

  • Poised lineage specification in multipotential hematopoietic stem and progenitor cells by the polycomb protein Bmi1.

    abstract::Polycomb group (PcG) proteins are essential regulators of stem cells. PcG and trithorax group proteins mark developmental regulator gene promoters with bivalent domains consisting of overlapping repressive and activating histone modifications to keep them poised for activation in embryonic stem cells. Bmi1, a componen...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Oguro H,Yuan J,Ichikawa H,Ikawa T,Yamazaki S,Kawamoto H,Nakauchi H,Iwama A

    更新日期:2010-03-05 00:00:00

  • Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells.

    abstract::Knowledge of both the global chromatin structure and the gene expression programs of human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) should provide a robust means to assess whether the genomes of these cells have similar pluripotent states. Recent studies have suggested that ESCs and iPSCs...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Guenther MG,Frampton GM,Soldner F,Hockemeyer D,Mitalipova M,Jaenisch R,Young RA

    更新日期:2010-08-06 00:00:00

  • PUMA regulates intestinal progenitor cell radiosensitivity and gastrointestinal syndrome.

    abstract::Radiation is one of the most effective cancer treatments. However, gastrointestinal (GI) syndrome is a major limiting factor in abdominal and pelvic radiotherapy. The loss of crypt stem cells or villus endothelial cells has been suggested to be responsible for radiation-induced intestinal damage. We report here a crit...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Qiu W,Carson-Walter EB,Liu H,Epperly M,Greenberger JS,Zambetti GP,Zhang L,Yu J

    更新日期:2008-06-05 00:00:00

  • Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds.

    abstract::Somatic cells can be induced into pluripotent stem cells (iPSCs) with a combination of four transcription factors, Oct4/Sox2/Klf4/c-Myc or Oct4/Sox2/Nanog/LIN28. This provides an enabling platform to obtain patient-specific cells for various therapeutic and research applications. However, several problems remain for t...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Shi Y,Desponts C,Do JT,Hahm HS,Schöler HR,Ding S

    更新日期:2008-11-06 00:00:00

  • Skinny Fat Cells Stimulate Wound Healing.

    abstract::In this issue of Cell Stem Cell, Shook et al. (2020) reveal that dermal adipocytes regulate skin wound repair via release of fatty acids that promote macrophage recruitment and accelerated revascularization. Furthermore, mature dermal adipocytes dedifferentiate into migratory extracellularmatrix-producing myofibroblas...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Merrick D,Seale P

    更新日期:2020-06-04 00:00:00

  • Primed for pluripotency.

    abstract::To date, pluripotent epiblast stem cells (EpiSCs) had only been derived from postimplantation mouse embryos. In this issue of Cell Stem Cell, Najm et al. (2011) demonstrate that EpiSCs can be routinely derived from preimplantation embryos, showing that both human and mouse blastocysts can produce the same class of pri...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Kunath T

    更新日期:2011-03-04 00:00:00

  • Imbalance between GABAergic and Glutamatergic Transmission Impairs Adult Neurogenesis in an Animal Model of Alzheimer's Disease.

    abstract::Adult neurogenesis regulates plasticity and function in the hippocampus, which is critical for memory and vulnerable to Alzheimer's disease (AD). Promoting neurogenesis may improve hippocampal function in AD brains. However, how amyloid beta (Abeta), the key AD pathogen, affects the development and function of adult-b...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Sun B,Halabisky B,Zhou Y,Palop JJ,Yu G,Mucke L,Gan L

    更新日期:2009-12-04 00:00:00

  • Position statement on the provision and procurement of human eggs for stem cell research.

    abstract::The nature of compensation for women who donate eggs (oocytes) for research remains a contentious issue internationally. This position paper lays out the arguments for, and discusses the arrangements in which, a modest payment might be ethically justifiable. ...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Haimes E,Skene L,Ballantyne AJ,Caulfield T,Goldstein LS,Hyun I,Kimmelman J,Robert JS,Roxland BE,Scott CT,Solbakk JH,Sugarman J,Taylor PL,Testa G,ISSCR.

    更新日期:2013-03-07 00:00:00

  • Synthetic Embryos: Windows into Mammalian Development.

    abstract::Mammalian embryonic stem cells (ESCs) can self-organize in vitro, but whether they can recreate early embryonic morphogenesis is unclear. Harrison et al. recently demonstrate in Science that 3D co-cultures of mouse ESCs and trophoblast stem cells self-organize into embryo-like structures that recreate many features of...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Warmflash A

    更新日期:2017-05-04 00:00:00

  • High-Throughput Screening Enhances Kidney Organoid Differentiation from Human Pluripotent Stem Cells and Enables Automated Multidimensional Phenotyping.

    abstract::Organoids derived from human pluripotent stem cells are a potentially powerful tool for high-throughput screening (HTS), but the complexity of organoid cultures poses a significant challenge for miniaturization and automation. Here, we present a fully automated, HTS-compatible platform for enhanced differentiation and...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Czerniecki SM,Cruz NM,Harder JL,Menon R,Annis J,Otto EA,Gulieva RE,Islas LV,Kim YK,Tran LM,Martins TJ,Pippin JW,Fu H,Kretzler M,Shankland SJ,Himmelfarb J,Moon RT,Paragas N,Freedman BS

    更新日期:2018-06-01 00:00:00

  • A Little Bit of Guidance: Mini Brains on Their Route to Adolescence.

    abstract::Cerebral organoids represent a new model in which to study human brain development outside the human body. Recently in Nature Biotechnology, Lancaster et al. (2017) tackled the lack of reproducibility, tissue homogeneity, and complexity of this system by bioengineering organoids to establish the next generation of hum...

    journal_title:Cell stem cell

    pub_type: 评论,杂志文章


    authors: Koch P,Ladewig J

    更新日期:2017-08-03 00:00:00

  • A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts.

    abstract::Epithelial-to-mesenchymal transition (EMT) is a developmental process important for cell fate determination. Fibroblasts, a product of EMT, can be reset into induced pluripotent stem cells (iPSCs) via exogenous transcription factors but the underlying mechanism is unclear. Here we show that the generation of iPSCs fro...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Li R,Liang J,Ni S,Zhou T,Qing X,Li H,He W,Chen J,Li F,Zhuang Q,Qin B,Xu J,Li W,Yang J,Gan Y,Qin D,Feng S,Song H,Yang D,Zhang B,Zeng L,Lai L,Esteban MA,Pei D

    更新日期:2010-07-02 00:00:00

  • Advances in Zika Virus Research: Stem Cell Models, Challenges, and Opportunities.

    abstract::The re-emergence of Zika virus (ZIKV) and its suspected link with various disorders in newborns and adults led the World Health Organization to declare a global health emergency. In response, the stem cell field quickly established platforms for modeling ZIKV exposure using human pluripotent stem cell-derived neural p...

    journal_title:Cell stem cell

    pub_type: 杂志文章,评审


    authors: Ming GL,Tang H,Song H

    更新日期:2016-12-01 00:00:00

  • A Pan-BCL2 inhibitor renders bone-marrow-resident human leukemia stem cells sensitive to tyrosine kinase inhibition.

    abstract::Leukemia stem cells (LSCs) play a pivotal role in the resistance of chronic myeloid leukemia (CML) to tyrosine kinase inhibitors (TKIs) and its progression to blast crisis (BC), in part, through the alternative splicing of self-renewal and survival genes. To elucidate splice-isoform regulators of human BC LSC maintena...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Goff DJ,Court Recart A,Sadarangani A,Chun HJ,Barrett CL,Krajewska M,Leu H,Low-Marchelli J,Ma W,Shih AY,Wei J,Zhai D,Geron I,Pu M,Bao L,Chuang R,Balaian L,Gotlib J,Minden M,Martinelli G,Rusert J,Dao KH,Shazand

    更新日期:2013-03-07 00:00:00

  • Direct Induction of Trophoblast Stem Cells from Murine Fibroblasts.

    abstract::Trophoblast stem cells (TSCs) arise from the first cell fate decision in the developing embryo and generate extra-embryonic lineages, giving rise to the fetal portion of the placenta. Mouse embryonic and extra-embryonic lineages are strictly separated by a distinct epigenetic barrier, which is not fully overcome follo...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Kubaczka C,Senner CE,Cierlitza M,Araúzo-Bravo MJ,Kuckenberg P,Peitz M,Hemberger M,Schorle H

    更新日期:2015-11-05 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

  • Rethinking stroma: lessons from the blood.

    abstract::Stroma is a largely understudied component of all organs that contributes to stem cell niches. Studies to define stromal components in the bone marrow have led to some unexpected findings that prompt further research. ...

    journal_title:Cell stem cell

    pub_type: 杂志文章


    authors: Scadden DT

    更新日期:2012-06-14 00:00:00