Abstract:
:Mammalian haploid embryonic stem cells (haESCs) hold great promise for functional genetic studies and forward screening. However, all established haploid cells are prone to spontaneous diploidization during long-term culture, rendering application challenging. Here, we report a genome-wide loss-of-function screening that identified gene mutations that could significantly reduce the rate of self-diploidization in haESCs. We further demonstrated that CRISPR/Cas9-mediated Etl4 knockout (KO) stabilizes the haploid state in different haESC lines. More interestingly, Etl4 deficiency increases mitochondrial oxidative phosphorylation (OXPHOS) capacity and decreases glycolysis in haESCs. Mimicking this effect by regulating the energy metabolism with drugs decreased the rate of self-diploidization. Collectively, our study identified Etl4 as a novel haploidy-related factor linked to an energy metabolism transition occurring during self-diploidization of haESCs.
journal_name
Stem Cell Reportsjournal_title
Stem cell reportsauthors
Zhang G,Li X,Sun Y,Wang X,Liu G,Huang Ydoi
10.1016/j.stemcr.2020.11.016subject
Has Abstractpub_date
2021-01-12 00:00:00pages
29-38issue
1issn
2213-6711pii
S2213-6711(20)30464-1journal_volume
16pub_type
杂志文章abstract::Research in human induced pluripotent stem cells (hiPSCs) is rapidly developing and there are expectations that this research may obviate the need to use human embryonic stem cells (hESCs), the ethics of which has been a subject of controversy for more than 15 years. In this study, we investigated approximately 3,400 ...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2015.03.002
更新日期:2015-05-12 00:00:00
abstract::Induced pluripotent stem cells were created from a pancreas agenesis patient with a mutation in GATA6. Using genome-editing technology, additional stem cell lines with mutations in both GATA6 alleles were generated and demonstrated a severe block in definitive endoderm induction, which could be rescued by re-expressio...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2016.12.026
更新日期:2017-03-14 00:00:00
abstract::Meiosis is the key step in gametogenesis. However, the mechanism of mammalian meiosis remains poorly understood due to the lack of an in vitro model. Here, we report that retinoic acid (RA) is sufficient for inducing leptotene/zygotene spermatocytes from cultured mouse spermatogonial stem cells. Multiple genes regulat...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2016.05.013
更新日期:2016-07-12 00:00:00
abstract::As complete absence of germ cells leads to sterile males in zebrafish, we explored the relationship between primordial germ cell (PGC) number and sexual development. Our results revealed dimorphic proliferation of PGCs in the early zebrafish larvae, marking the beginning of sexual differentiation. We applied morpholin...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2014.10.011
更新日期:2015-01-13 00:00:00
abstract::Deletion of caudal/cdx genes alters hox gene expression and causes defects in posterior tissues and hematopoiesis. Yet, the defects in hox gene expression only partially explain these phenotypes. To gain deeper insight into Cdx4 function, we performed chromatin immunoprecipitation sequencing (ChIP-seq) combined with g...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2013.10.001
更新日期:2013-11-07 00:00:00
abstract::Primitive erythropoiesis follows a stereotypic developmental program of mesoderm ventralization and internalization, hemangioblast formation and migration, and erythroid lineage specification. Induction of erythropoiesis is inefficient in either ES/iPS cells in vitro or nonhemangioblast cell populations in vivo. Using...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2014.01.019
更新日期:2014-03-06 00:00:00
abstract::Pelizaeus-Merzbacher disease (PMD) is a fatal X-linked disorder caused by loss of myelinating oligodendrocytes and consequent hypomyelination. The underlying cellular and molecular dysfunctions are not fully defined, but therapeutic enhancement of oligodendrocyte survival could restore functional myelination in patien...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.07.015
更新日期:2018-09-11 00:00:00
abstract::Genetic changes in human pluripotent stem cells (hPSCs) gained during culture can confound experimental results and potentially jeopardize the outcome of clinical therapies. Particularly common changes in hPSCs are trisomies of chromosomes 1, 12, 17, and 20. Thus, hPSCs should be regularly screened for such aberration...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2016.10.003
更新日期:2016-11-08 00:00:00
abstract::In human-to-mouse xenograft models, reconstitution of human hematopoiesis is usually B-lymphoid dominant. Here we show that the introduction of homozygous Kit(Wv) mutations into C57BL/6.Rag2(null)Il2rg(null) mice with NOD-Sirpa (BRGS) strongly promoted human multi-lineage reconstitution. After xenotransplantation of h...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2016.07.002
更新日期:2016-09-13 00:00:00
abstract::Diminished mitochondrial function is causally related to some heart diseases. Here, we developed a human disease model based on cardiomyocytes from human embryonic stem cells (hESCs), in which an important pathway of mitochondrial gene expression was inactivated. Repression of PGC-1α, which is normally induced during ...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2013.11.008
更新日期:2013-12-12 00:00:00
abstract::The core pluripotency transcription factor NANOG is critical for embryonic stem cell (ESC) self-renewal and somatic cell reprogramming. Although NANOG is phosphorylated at multiple residues, the role of NANOG phosphorylation in ESC self-renewal is incompletely understood, and no information exists regarding its functi...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2017.03.023
更新日期:2017-05-09 00:00:00
abstract::Nerve-derived neural crest cells are essential for regeneration in certain animals, such as newts. Here, we asked whether they play a similar role during mammalian tissue repair, focusing on Sox2-positive neural crest precursors in skin. In adult skin, Sox2 was expressed in nerve-terminal-associated neural crest precu...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2013.04.004
更新日期:2013-06-04 00:00:00
abstract::Being able to summarize properly your work is not an easy task. But learning the skill of writing a good abstract is very important, as it can open many doors, including the possibility to be selected as a speaker at conferences. As meeting abstract reviewers, here we are writing to give you insights into the abstract...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.11.016
更新日期:2018-12-11 00:00:00
abstract::Activation of Wnt/β-catenin signaling can induce both self-renewal and differentiation in naive pluripotent embryonic stem cells (ESCs). To gain insights into the mechanism by which Wnt/β-catenin regulates ESC fate, we screened and characterized its downstream targets. Here, we show that the self-renewal-promoting eff...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2015.07.014
更新日期:2015-09-08 00:00:00
abstract::Reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs) entails a mesenchymal to epithelial transition (MET). While attempting to dissect the mechanism of MET during reprogramming, we observed that knockdown (KD) of the epithelial-to-mesenchymal transition (EMT) factor SNAI1 (SNAIL) paradoxically reduce...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2014.09.008
更新日期:2014-11-11 00:00:00
abstract::Although the functional roles of long noncoding RNAs (lncRNAs) have been increasingly identified, few lncRNAs that control the naïve state of embryonic stem cells (ESCs) are known. Here, we report a naïve-state-associated lncRNA, LincU, which is intrinsically activated by Nanog in mESCs. LincU-deficient mESCs exhibit ...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.06.010
更新日期:2018-08-14 00:00:00
abstract::Pro-fibrotic microenvironments of scars and tumors characterized by increased stiffness stimulate mesenchymal stromal cells (MSCs) to express α-smooth muscle actin (α-SMA). We investigated whether incorporation of α-SMA into contractile stress fibers regulates human MSC fate. Sorted α-SMA-positive MSCs exhibited high ...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2015.05.004
更新日期:2015-06-09 00:00:00
abstract::Mitochondria are critical to neurogenesis, but the mechanisms of mitochondria in neurogenesis have not been well explored. We fully characterized mitochondrial alterations and function in relation to the development of human induced pluripotent stem cell (hiPSC)-derived dopaminergic (DA) neurons. Following directed di...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2016.08.014
更新日期:2016-10-11 00:00:00
abstract::We identified osteoclast defects in craniometaphyseal dysplasia (CMD) using an easy-to-use protocol for differentiating osteoclasts from human induced pluripotent stem cells (hiPSCs). CMD is a rare genetic bone disorder, characterized by life-long progressive thickening of craniofacial bones and abnormal shape of long...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2017.09.016
更新日期:2017-11-14 00:00:00
abstract::Several studies have reported an association between the farnesoid X receptor alpha (FXRα) and estrogenic signaling pathways. Fxrα could thus be involved in the reprotoxic effects of endocrine disruptors such as bisphenol-A (BPA). To test this hypothesis, mice were exposed to BPA and/or stigmasterol (S), an FXRα antag...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.08.018
更新日期:2018-10-09 00:00:00
abstract::Dynamic spatiotemporal modification of chromatin around DNA damage is vital for efficient DNA repair. Normal stem cells exhibit an attenuated DNA damage response (DDR), inefficient DNA repair, and high radiosensitivity. The impact of unique chromatin characteristics of stem cells in DDR regulation is not yet recognize...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2016.11.004
更新日期:2016-12-13 00:00:00
abstract::Hematopoietic stem cells (HSCs) exist in a dormant state and progressively lose regenerative potency as they undergo successive divisions. Why this functional decline occurs and how this information is encoded is unclear. To better understand how this information is stored, we performed RNA sequencing on HSC populatio...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2020.03.005
更新日期:2020-04-14 00:00:00
abstract::Following Jamie Thomson's lecture on primate embryonic stem cells (ESCs) at a meeting I had organized in March 1997, in Israel, to celebrate receipt of the Wolf Prize in Agriculture to my colleague and friend Neal First, frozen human embryos donated for research in Israel were shipped to Wisconsin. The five hESC lines...
journal_title:Stem cell reports
pub_type: 杂志文章,评审
doi:10.1016/j.stemcr.2018.04.011
更新日期:2018-05-08 00:00:00
abstract::Hematopoietic stem cells (HSCs) ensure a life-long regeneration of the blood system and are therefore an important source for transplantation and gene therapy. The teratoma environment supports the complex development of functional HSCs from human pluripotent stem cells, which is difficult to recapitulate in culture. ...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.09.010
更新日期:2018-11-13 00:00:00
abstract::The International Society for Stem Cell Research 11(th) Annual Meeting was held in Boston in June 2013, bringing together just over 4000 attendees. An emphasis on therapeutic applications in many talks reflected the maturation of the stem cell field from its origins in basic science to one that is beginning to show th...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2013.12.004
更新日期:2013-01-01 00:00:00
abstract::Although pluripotent stem cells can generate various types of differentiated cells, it is unclear why lineage-committed stem/progenitor cells derived from pluripotent stem cells are decelerated and why the differentiation-resistant propensity of embryonic stem cell (ESC)/induced pluripotent stem cell (iPSC)-derived ce...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.12.018
更新日期:2019-02-12 00:00:00
abstract::Fanconi anemia (FA) causes bone marrow failure early during childhood, and recent studies indicate that a hematopoietic defect could begin in utero. We performed a unique kinetics study of hematopoiesis in Fancg-/- mouse embryos, between the early embryonic day 11.5 (E11.5) to E12.5 developmental window (when the high...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.10.001
更新日期:2018-11-13 00:00:00
abstract::Long-term survival and integration of neural progenitor cells (NPCs) transplanted following spinal cord injury (SCI) have been observed. However, questions concerning the differentiation choice, the mechanism of action, and the contribution of NPCs to functional recovery remains unanswered. Therefore, we investigated ...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2019.03.013
更新日期:2019-05-14 00:00:00
abstract::Human stem cell-derived models of development and neurodegenerative diseases are challenged by cellular immaturity in vitro. Microengineered organ-on-chip (or Organ-Chip) systems are designed to emulate microvolume cytoarchitecture and enable co-culture of distinct cell types. Brain microvascular endothelial cells (BM...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.02.012
更新日期:2018-04-10 00:00:00
abstract::Human pluripotent stem cell-derived vascular smooth muscle cells (hPSC-VSMCs) are of great value for disease modeling, drug screening, cell therapies, and tissue engineering. However, producing a high quantity of hPSC-VSMCs with current cell culture technologies remains very challenging. Here, we report a scalable met...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.11.009
更新日期:2019-01-08 00:00:00