Abstract:
:The recent development of targeted murine reporter alleles as proxies for intestinal stem cell activity has led to significant advances in our understanding of somatic stem cell hierarchies and dynamics. Analysis of these reporters has led to a model in which an indispensable reserve stem cell at the top of the hierarchy (marked by Bmi1 and Hopx reporters) gives rise to active intestinal stem cells (marked by an Lgr5 reporter). Despite these advances, controversy exists regarding the specificity and fidelity with which these alleles distinguish intestinal stem cell populations. Here, we undertake a comprehensive comparison of widely used proxy reporters including both CreERT2 and EGFP cassettes targeted to the Lgr5, Bmi1, and Hopx loci. Single-cell transcriptional profiling of these populations and their progeny reveals that reserve and active intestinal stem cells are molecularly and functionally distinct, supporting a two-stem-cell model for intestinal self-renewal.
journal_name
Stem Cell Reportsjournal_title
Stem cell reportsauthors
Li N,Yousefi M,Nakauka-Ddamba A,Jain R,Tobias J,Epstein JA,Jensen ST,Lengner CJdoi
10.1016/j.stemcr.2014.09.011subject
Has Abstractpub_date
2014-11-11 00:00:00pages
876-91issue
5issn
2213-6711pii
S2213-6711(14)00296-3journal_volume
3pub_type
杂志文章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::Human mesenchymal stem cells (hMSCs), which conventionally are isolated based on their adherence to plastic, are heterogeneous and have poor growth and differentiation, limiting our ability to investigate their intrinsic characteristics. We report an improved prospective clonal isolation technique and reveal that the ...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2013.06.001
更新日期:2013-07-11 00:00:00
abstract::Stem cell-derived somatic cells represent an unlimited resource for basic and translational science. Although promising, there are significant hurdles that must be overcome. Our focus is on the generation of the major cell type of the human liver, the hepatocyte. Current protocols produce variable populations of hepat...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2015.10.016
更新日期:2015-12-08 00:00:00
abstract::Tight regulation of the balance between self-renewal and differentiation of neural stem cells is crucial to assure proper neural development. In this context, Notch signaling is a well-known promoter of stemness. In contrast, the bifunctional brain-enriched microRNA miR-9/9(∗) has been implicated in promoting neuronal...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2016.06.008
更新日期:2016-08-09 00:00:00
abstract::High-purity cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) are promising for drug development and myocardial regeneration. However, most hiPSC-derived CMs morphologically and functionally resemble immature rather than adult CMs, which could hamper their application. Here, we obtained h...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2017.09.007
更新日期:2017-11-14 00:00:00
abstract::The microenvironment is a critical mediator of stem cell survival, proliferation, migration, and differentiation. The majority of preclinical studies involving transplantation of neural stem cells (NSCs) into the CNS have focused on injured or degenerating microenvironments, leaving a dearth of information as to how N...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2014.03.005
更新日期:2014-04-18 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::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::Alzheimer's disease (AD) induces memory and cognitive impairment in the absence of motor and sensory deficits during its early and middle course. A major unresolved question is the basis for this selective neuronal vulnerability. Aβ, which plays a central role in AD pathogenesis, is generated throughout the brain, yet...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2017.10.015
更新日期:2017-12-12 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::Non-human primates (NHPs) can serve as a human-like model to study cell therapy using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). However, whether the efficacy of NHP and human iPSC-CMs is mechanistically similar remains unknown. To examine this, RNU rats received intramyocardial injection of 1 × ...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.01.002
更新日期:2018-02-13 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::The transcription factor (TF) GATA2 plays a key role in organ development and cell fate control in the central nervous, urogenital, respiratory, and reproductive systems, and in primitive and definitive hematopoiesis. Here, we generate a knockin protein reporter mouse line expressing a GATA2VENUS fusion from the endog...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2020.06.008
更新日期:2020-08-11 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 induced pluripotent stem cell (hiPSC) culture has become routine, yet the cost of pluripotent cell media, frequent medium changes, and the reproducibility of differentiation have remained restrictive. Here, we describe the formulation of a hiPSC culture medium (B8) as a result of the exhaustive optimization of m...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2019.12.007
更新日期:2020-02-11 00:00:00
abstract::Developing effective therapeutics for complex diseases such as late-onset, sporadic Alzheimer's disease (SAD) is difficult due to genetic and environmental heterogeneity in the human population and the limitations of existing animal models. Here, we used hiPSC-derived neurons to test a compound that stabilizes the ret...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.01.031
更新日期:2018-03-13 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::BACE1 is validated as Alzheimer's β-secretase and a therapeutic target for Alzheimer's disease. In examining BACE1-null mice, we discovered that BACE1 deficiency develops abnormal clusters of immature neurons, forming doublecortin-positive neuroblasts, in the developing dentate gyrus, mainly in the subpial zone (SPZ)....
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2017.05.030
更新日期:2017-07-11 00:00:00
abstract::A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neura...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2014.09.004
更新日期:2014-11-11 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::B-lymphocyte-induced nuclear maturation protein 1 (BLIMP1) was previously reported to define a sebaceous gland (SG) progenitor population in the epidermis. However, the recent identification of multiple stem cell populations in the hair follicle junctional zone has led us to re-evaluate its function. We show, in agree...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2014.08.007
更新日期:2014-10-14 00:00:00
abstract::Precise methods for transgene regulation are important to study signaling pathways and cell lineages in biological systems where gene function is often recycled within and across lineages. We engineered a genetic toolset for flexible transgene regulation in these diverse cellular contexts. Specifically, we created an ...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2015.01.013
更新日期:2015-03-10 00:00:00
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 t...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2020.11.016
更新日期:2021-01-12 00:00:00
abstract::Contractile to synthetic phenotypic switching of smooth muscle cells (SMCs) contributes to stenosis in vascular disease and vascular transplants. To generate more contractile SMCs, we performed a high-throughput differentiation screen using a MYH11-NLuc-tdTomato human embryonic stem cell reporter cell line. We identif...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2019.04.013
更新日期:2019-06-11 00:00:00
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::Standardization of mesenchymal stromal cells (MSCs) remains a major obstacle in regenerative medicine. Starting material and culture expansion affect cell preparations and render comparison between studies difficult. In contrast, induced pluripotent stem cells (iPSCs) assimilate toward a ground state and may therefore...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2014.07.003
更新日期:2014-09-09 00:00:00
abstract::Thick-filament sarcomere mutations are a common cause of hypertrophic cardiomyopathy (HCM), a disorder of heart muscle thickening associated with sudden cardiac death and heart failure, with unclear mechanisms. We engineered four isogenic induced pluripotent stem cell (iPSC) models of β-myosin heavy chain and myosin-b...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2018.11.015
更新日期:2019-01-08 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::ADP-ribosylation factor-like 4aa (Arl4aa) is a member of the ADP-ribosylation factor family. It is expressed in hematopoietic tissue during embryonic development, but its function was unknown. Zebrafish arl4aa is preferentially expressed in the ventral wall of the dorsal aorta (VDA) at 24 and 36 hpf and in caudal hema...
journal_title:Stem cell reports
pub_type: 杂志文章
doi:10.1016/j.stemcr.2020.02.012
更新日期:2020-04-14 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