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Showing papers in "Cell Stem Cell in 2021"


Journal ArticleDOI
TL;DR: In this paper, it was shown that human naive embryonic stem cells readily make blastocyst trophectoderm and descendant trophoblast cell types, and they were induced rapidly and efficiently by inhibition of ERK/mitogenactivated protein kinase (MAPK) and Nodal signaling.

145 citations


Journal ArticleDOI
TL;DR: It is shown that mouse embryonic stem cells (mESCs) can be coaxed to robustly undergo fundamental steps of early heart organogenesis with an in-vivo-like spatiotemporal fidelity and unveil the surprising morphogenetic potential of mESCs to execute key aspects of organogenesis through the coordinated development of multiple tissues.

141 citations


Journal ArticleDOI
TL;DR: ApoE4, a strong genetic risk factor for Alzheimer disease, has been associated with increased risk for severe COVID-19 as discussed by the authors, but it is unclear whether ApoE4 alters COVID19 susceptibility or severity, and the role of direct viral infection in brain cells remains obscure.

124 citations


Journal ArticleDOI
TL;DR: In this paper, the authors applied single-cell RNA sequencing (scRNA-seq) and single cell assay for transposase-accessible chromatin sequencing to over 8,000 human immunophenotypic blood cells from fetal liver and bone marrow.

122 citations


Journal ArticleDOI
TL;DR: In this article, the authors show that IFNγ signaling induced during chronic infection can drive DNMT3a-loss-of-function CH in mouse chimeras, which is a risk factor for malignancy, cardiovascular disease, and all cause mortality.

117 citations


Journal ArticleDOI
TL;DR: In this paper, the authors describe a human embryo model (blastoid) generated by self-organization, which is composed of three tissue layers displaying exclusive lineage markers, mimicking the natural blastocyst.

116 citations


Journal ArticleDOI
TL;DR: In this article, naive human pluripotent stem cells (PSCs) were shown to recapitulate trophoblast development, demonstrating the invaluable properties of naive human PSCs.

114 citations


Journal ArticleDOI
TL;DR: Stem cells derived from formative mouse epiblast show distinct transcription factor dependencies, relying critically on Otx2, and cell culture conditions applied to human naive cells or embryos support expansion of similar stem cells, consistent with a conserved staging post on the trajectory of mammalian pluripotency.

112 citations


Journal ArticleDOI
TL;DR: In this article, the authors focus on key conceptual ideas on how mitochondria control mammalian stem cell fate and function through reactive oxygen species (ROS) generation, TCA cycle metabolite production, NAD+/NADH ratio regulation, pyruvate metabolism, and mitochondrial dynamics.

104 citations


Journal ArticleDOI
TL;DR: This article quantified the effect of the JAK2-V617F mutation on the self-renewal and differentiation dynamics of HSCs in treatment-naive individuals with myeloproliferative neoplasms and reconstructed lineage histories of individual hematopoietic stem cells using somatic mutation patterns.

102 citations


Journal ArticleDOI
TL;DR: Shapiro et al. as discussed by the authors evaluated the safety and efficacy of pancreatic endoderm cells (PECs) implanted in non-immunoprotective macroencapsulation devices for the treatment of type 1 diabetes.


Journal ArticleDOI
TL;DR: It is shown that a mechanically triggered increase in endocytosis regulates early differentiation, and is of fundamental importance for understanding how cell mechanics regulates biochemical signaling and therefore cell fate.

Journal ArticleDOI
TL;DR: This article showed that CSCs upregulate the immune checkpoint molecule CD276 (B7-H3) to evade host immune responses and showed that anti-CD276 antibodies eliminate CSC in a CD8+ T-cell-dependent manner, inhibiting tumor growth and lymph node metastases in a mouse HNSCC model.

Journal ArticleDOI
TL;DR: By modulating fibroblast growth factor (FGF), transforming growth factor β (TGF-β), and WNT pathways, PSCs are derived from mice, horses, and humans (designated as XPSCs) that are permissive for direct PGC-like cell induction in vitro and are capable of contributing to intra- or inter-species chimeras in vivo.


Journal ArticleDOI
TL;DR: This work uses single-cell mRNA sequencing with in situ validation approaches to interrogate human intestinal development from 7-21 weeks post conception, assigning molecular identities and spatial locations to cells and factors that comprise the niche.


Journal ArticleDOI
TL;DR: In this paper, the authors show that neural stem cells in young adults return to a shallow quiescence and progress through additional self-renewing divisions in adulthood, ensuring lifelong hippocampal neurogenesis.

Journal ArticleDOI
TL;DR: In this article, the authors profiled and analyzed ∼32,500 single-cell transcriptomes of testicular cells from embryonic, fetal, and infant stages, and revealed multiple insights into the coordinated and temporal development of the embryonic and fetal male germline together with the somatic niche.

Journal ArticleDOI
TL;DR: In this paper, the midbrain dopamine neuron grafts from human embryonic stem cells and manufactured large-scale cryopreserved dopamine progenitors for clinical use were used for Parkinson's disease.


Journal ArticleDOI
TL;DR: In this article, a two-step WNT signaling activation strategy was proposed to improve expression of midbrain markers, such as Engrailed-1 (EN1), while minimizing expression of contaminating posterior (hindbrain) and anterior (diencephalic) lineage markers.

Journal ArticleDOI
TL;DR: Using direct conversion of AD patient fibroblasts into induced neurons (iNs), the authors generated an age-equivalent neuronal model and found that iNs exhibit strong neuronal transcriptome signatures characterized by downregulation of mature neuronal properties and upregulation of immature and progenitor-like signaling pathways.

Journal ArticleDOI
TL;DR: In this article, potential mechanisms of action for the therapeutic effects of mesenchymal stromal cells transplantation, experimental models that dissect tissue modulating function of MSCs, and approaches for identifying MSC effects in vivo by integrating biomarkers of disease and MSC activity.

Journal ArticleDOI
TL;DR: Single-cell RNA sequencing of human MKs from embryonic yolk sac and fetal liver is used to characterize the transcriptome, cellular heterogeneity, and developmental trajectories of early megakaryopoiesis and identifies a subpopulation of CD42b+CD14+ MKs in vivo that exhibit high expression of genes associated with immune responses.

Journal ArticleDOI
TL;DR: Results indicate similarity in cell-type-specific pre- and post-synaptic integration between transplant-reconstructed circuit and endogenous neural networks, highlighting the capacity of hPSC-derived neuron subtypes for specific circuit repair and functional restoration in the adult brain.

Journal ArticleDOI
TL;DR: The data identify a signaling pathway promoting NSC alertness and add to the emerging concept that SCs can respond to the systemic milieu.

Journal ArticleDOI
TL;DR: In this article, the authors compared human microglia states across culture models, including cultured primary and pluripotent stem cell-derived micro-glia, and developed a "report card" of gene expression signatures across these distinct models to facilitate characterization of their responses across experimental models, perturbations, and disease conditions.

Journal ArticleDOI
TL;DR: CAST-Seq is a sensitive assay able to identify and quantify unintended chromosomal rearrangements in addition to the more typical mutations at off-target sites, and may be particularly relevant for therapeutic genome editing to enable thorough risk assessment before clinical application of gene-edited products.