Abstract：
:While gene expression dynamics have been extensively cataloged during hematopoietic differentiation in the adult, less is known about transcriptome diversity of human hematopoietic stem cells (HSCs) during development. To characterize transcriptional and post-transcriptional changes in HSCs during development, we leveraged high-throughput genomic approaches to profile miRNAs, lincRNAs, and mRNAs. Our findings indicate that HSCs manifest distinct alternative splicing patterns in key hematopoietic regulators. Detailed analysis of the splicing dynamics and function of one such regulator, HMGA2, identified an alternative isoform that escapes miRNA-mediated targeting. We further identified the splicing kinase CLK3 that, by regulating HMGA2 splicing, preserves HMGA2 function in the setting of an increase in let-7 miRNA levels, delineating how CLK3 and HMGA2 form a functional axis that influences HSC properties during development. Collectively, our study highlights molecular mechanisms by which alternative splicing and miRNA-mediated post-transcriptional regulation impact the molecular identity and stage-specific developmental features of human HSCs.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Cesana M,Guo MH,Cacchiarelli D,Wahlster L,Barragan J,Doulatov S,Vo LT,Salvatori B,Trapnell C,Clement K,Cahan P,Tsanov KM,Sousa PM,Tazon-Vega B,Bolondi A,Giorgi FM,Califano A,Rinn JL,Meissner A,Hirschhorn JN,Daleydoi
10.1016/j.stem.2018.03.012subject
Has Abstractpub_date
2018-04-05 00:00:00pages
575-588.e7issue
4eissn
1934-5909issn
1875-9777pii
S1934-5909(18)30118-8journal_volume
22pub_type
杂志文章相关文献
Cell Stem Cell文献大全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
doi：10.1016/j.stem.2016.11.014
更新日期：2016-12-01 00:00:00
abstract：:Developing technologies for efficient and scalable disruption of gene expression will provide powerful tools for studying gene function, developmental pathways, and disease mechanisms. Here, we develop clustered regularly interspaced short palindromic repeat interference (CRISPRi) to repress gene expression in human i...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2016.01.022
更新日期：2016-04-07 00:00:00
abstract：:Exit from the naive pluripotent state occurs through a series of changes in the gene regulatory circuitry, allowing cells to become primed for lineage commitment. In this issue of Cell Stem Cell, Kalkan et al. (2019) show that three transcription regulators are required for naive mouse embryonic stem cells (ESCs) to e...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2019.04.008
更新日期：2019-05-02 00:00:00
abstract：:Stem cells have the capacity to both self-renew and generate postmitotic cells. Long-term tracking of individual clones in their natural environment constitutes the ultimate way to validate postembryonic stem cells. We identify retinal stem cells (RSCs) using the spatiotemporal organization of the fish retina and foll...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2011.11.004
更新日期：2011-12-02 00:00:00
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
doi：10.1016/j.stem.2010.04.014
更新日期：2010-07-02 00:00:00
abstract：:The suspected link between infection by Zika virus (ZIKV), a re-emerging flavivirus, and microcephaly is an urgent global health concern. The direct target cells of ZIKV in the developing human fetus are not clear. Here we show that a strain of the ZIKV, MR766, serially passaged in monkey and mosquito cells efficientl...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2016.02.016
更新日期：2016-05-05 00:00:00
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
doi：10.1016/j.stem.2018.03.006
更新日期：2018-04-05 00:00:00
abstract：:The discovery that phenotypic diversity among differentiated cells results from epigenetic and not genetic differences, and can be reset to restore pluripotency, promises revolutionary advances in medicine. I discuss how this and related seminal discoveries have brought us to an exciting future. ...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2012.11.014
更新日期：2012-12-07 00:00:00
abstract：:Stem cell researchers commonly use human pluripotent stem cell lines derived by other investigators. Researchers may use lines derived elsewhere, provided that their derivation met consensus core standards. Some types of derivation raise heightened levels of ethical concern and require greater scrutiny. To maintain pu...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2009.01.013
更新日期：2009-02-06 00:00:00
abstract：:Ezh2, the methyltransferase within Polycomb Repressive II Complexes, was thought to be essential for all H3K27me3 marks in embryonic stem cells (ESCs). Recently in Molecular Cell, Shen and colleagues (2008) revealed that EZH2 is dispensable for ESC derivation and self-renewal, and that EZH1 may unexpectedly compensate...
journal_title：Cell stem cell
pub_type： 杂志文章,评审
doi：10.1016/j.stem.2008.11.007
更新日期：2008-12-04 00:00:00
abstract：:The maintenance of a pool of quiescent satellite cells (muscle stem cells) is necessary for long-term muscle health. In this issue of Cell Stem Cell, Verma et al. (2018) show that satellite cells recruit endothelial cells to create a vascular niche and that cross-talk between endothelial and satellite cells is vital f...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2018.09.013
更新日期：2018-10-04 00:00:00
abstract：:Mouse embryonic stem cells (mESCs) cultured under serum/LIF conditions exhibit heterogeneous expression of pluripotency-associated factors that can be overcome by two inhibitors (2i) of the MEK and GSK3 pathways. Several studies have shown that the "ground state" induced by 2i is characterized by global hypomethylatio...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2015.07.005
更新日期：2015-10-01 00:00:00
abstract：:The transcription factors Tcf3 and Nanog regulate many genes in embryonic stem cells, but according to two reports in this issue of Cell Stem Cell (Festuccia et al., 2012, Martello et al., 2012), only one, Esrrb, encoding an orphan nuclear hormone receptor, truly matters in the maintenance of self-renewal. ...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2012.09.005
更新日期：2012-10-05 00:00:00
abstract：:Like politics, most developmental signals are local. However, in this issue of Cell Stem Cell, Kwan et al. (2016) and colleagues describe how a stress-induced signal that originates in the zebrafish brain promotes the formation of blood at a distant site, the dorsal aorta. ...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2016.08.011
更新日期：2016-09-01 00:00:00
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
doi：10.1016/j.stem.2017.07.001
更新日期：2017-08-03 00:00:00
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
doi：10.1016/j.stem.2015.04.009
更新日期：2015-05-07 00:00:00
abstract：:A crucial limitation to our understanding of Alzheimer's disease has been the inability to test hypotheses on live, patient-specific neurons. A recent study in Nature by Israel et al. (2012) reports that iPSC-derived neurons from AD patients recapitulate multiple aspects of disease pathology. ...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2012.02.011
更新日期：2012-03-02 00:00:00
abstract：:COVID-19 has unfortunately halted lab work, conferences, and in-person networking, which is especially detrimental to researchers just starting their labs. Through social media and our reviewer networks, we met some early-career stem cell investigators impacted by the closures. Here, they introduce themselves and thei...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2020.06.011
更新日期：2020-07-02 00:00:00
abstract：:Two recent papers outline improvements in gene editing technology that may facilitate the analysis of signaling networks important for development. The systems developed by both Thyagarajan and coworkers (Thyagarajan et al., 2007) in Nature Biotechnology, and Lombardo and colleagues (Lombardo et al., 2007) in Stem Cel...
journal_title：Cell stem cell
pub_type： 杂志文章,评审
doi：10.1016/j.stem.2007.11.004
更新日期：2007-12-13 00:00:00
abstract：:Centralized banking of human embryonic stem (hES) cells is an endeavor that can benefit individual research efforts and enhance international collaboration but is complicated by the fact that the science is rapidly evolving in an environment of heterogeneous laws, guidelines, and ethical standards. Written from the va...
journal_title：Cell stem cell
pub_type： 杂志文章,评审
doi：10.1016/j.stem.2008.03.018
更新日期：2008-04-10 00:00:00
abstract：:Precise lineage trajectories and the cellular sources that contribute to regeneration after injury are largely unknown in many tissues. In this issue of Cell Stem Cell, Gadye et al. (2017) and Lin et al. (2017) show that olfactory epithelial cells transit through unique and unfamiliar paths of differentiation and unde...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2017.11.014
更新日期：2017-12-07 00:00:00
abstract：:We are only beginning to understand the higher-order chromatin structure of pluripotent stem cells and its relevance to cell fate. Three recent studies used different approaches to reconstruct the 3D chromatin landscape of naive and primed pluripotent cells, unveiling common features as well as differences between the...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2016.01.014
更新日期：2016-02-04 00:00:00
abstract：:In this issue of Cell Stem Cell, Belema-Bedada et al. (2008) describe a novel mechanism by which bone marrow-derived adult mesenchymal stem cells migrate to sites of damaged heart tissue. This process is dependent on the intracellular adaptor molecule FROUNT, which interacts with the chemokine receptor CCR2. ...
journal_title：Cell stem cell
pub_type： 评论
doi：10.1016/j.stem.2008.05.012
更新日期：2008-06-05 00:00:00
abstract：:Prognostic markers that capture leukemia stem cell (LSC) activity can be useful for the risk stratification of acute myeloid leukemia (AML) patients. In a recent issue of Nature, Ng et al. (2016) develop a prognostic score based on a 17-gene expression signature of LSCs to predict outcome in AML patients. ...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2017.02.010
更新日期：2017-03-02 00:00:00
abstract：:Tissue homeostasis over the life of an organism relies on both self-renewal and multipotent differentiation of stem cells. Hematopoietic stem cells (HSCs) reside in a hypoxic bone marrow environment, and their metabolic status is distinct from that of their differentiated progeny. HSCs generate energy mainly via anaer...
journal_title：Cell stem cell
pub_type： 杂志文章,评审
doi：10.1016/j.stem.2011.09.010
更新日期：2011-10-04 00:00:00
abstract：:In Nature Medicine, Pollyea et al. (2018) recently reported a remarkable overall response of newly diagnosed elderly acute myeloid leukemia patients to a venetoclax and azacitidine combination in a new clinical trial. This treatment reduced succinate dehydrogenase glutathionylation, impaired the tricarboxylic acid cyc...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2018.12.005
更新日期：2019-01-03 00:00:00
abstract：:In this study, we used whole-genome sequencing and gene expression profiling of 215 human induced pluripotent stem cell (iPSC) lines from different donors to identify genetic variants associated with RNA expression for 5,746 genes. We were able to predict causal variants for these expression quantitative trait loci (e...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2017.03.009
更新日期：2017-04-06 00:00:00
abstract：:Tumors contain hostile inflammatory signals generated by aberrant proliferation, necrosis, and hypoxia. These signals are sensed and acted upon acutely by the Toll-like receptors (TLRs) to halt proliferation and activate an immune response. Despite the presence of TLR ligands within the microenvironment, tumors progre...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2016.12.001
更新日期：2017-04-06 00:00:00
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
doi：10.1016/j.stem.2016.06.005
更新日期：2016-07-07 00:00:00
abstract：:Chimeras are individuals with tissues derived from more than one zygote. Interspecific chimeras have tissues derived from different species. The biological consequences of human-animal chimeras have become an issue of ethical debate. Ironically, human-animal chimeras with human blood, neurons, germ cells, and other ti...
journal_title：Cell stem cell
pub_type： 杂志文章,评审
doi：10.1016/j.stem.2007.07.021
更新日期：2007-09-13 00:00:00
