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Updated: 38 min 48 sec ago

Direct Conversion of Mouse Fibroblasts into Cholangiocyte Progenitor Cells

Thu, 03/29/2018 - 00:00
In this article, Han and colleagues revisited the roles of HepSC-specific factors and found that Hnf1α and Foxa3 facilitate the robust conversion into iHepSCs displaying a relatively closer transcriptional pattern with LEPCs. The prolonged in vitro culture of iHepSCs induces Notch-mediated secondary conversion into iCPCs, which could efficiently be differentiated into mature cholangiocytes.

Heterogeneity of Human Breast Stem and Progenitor Cells as Revealed by Transcriptional Profiling

Thu, 03/29/2018 - 00:00
In this article, Colacino and colleagues use flow-cytometry-sorted populations and single-cell analyses to investigate human mammary stem cells. They discover unexpected phenotypic and functional heterogeneity at the single-cell level, including a subpopulation of ALDH+ stem cells with a hybrid epithelial/mesenchymal phenotype and triple-negative breast cancer-like gene expression pattern.

Promoting Myelin Repair through In Vivo Neuroblast Reprogramming

Thu, 03/29/2018 - 00:00
Durbec and colleagues highlight the fate plasticity of neuroblasts in mouse brain after demyelination. They show that a subset of neuroblasts produced in SVZ spontaneously convert into oligodendrocytes after demyelination. They furthermore demonstrate that myelin regeneration can be enhanced by forcing this spontaneous conversion through in-vivo-directed cell reprogramming by forced expression of Olig2 and Sox10 in endogenous neuroblasts.

Far Upstream Element-Binding Protein 1 Regulates LSD1 Alternative Splicing to Promote Terminal Differentiation of Neural Progenitors

Thu, 03/29/2018 - 00:00
In this article, Paik and colleagues demonstrate that FUBP1 plays an indispensable role in promoting terminal differentiation of neurons and that lack of FUBP1 interferes with early-born neuronal cells exiting the cell cycle and predisposes these cells for transformation. These findings explain how FUBP1 serves uniquely as a tumor suppressor in the CNS.

Matched Developmental Timing of Donor Cells with the Host Is Crucial for Chimera Formation

Thu, 03/29/2018 - 00:00
Cohen at al. compares the efficiency of chimera formation in heterochronic and isochronic injections of ESCs and NCCs. Using two distinct and well-characterized pre- and post-implantation chimeric platforms, they show that matching of developmental age of donor cells and the host is essential for chimera formation.

Functional Studies of Missense TREM2 Mutations in Human Stem Cell-Derived Microglia

Thu, 03/29/2018 - 00:00
Brownjohn and colleagues report methods to generate microglia from induced pluripotent human stem cells, which they demonstrate are highly similar to cultured primary human microglia. Microglia differentiated from patient-derived stem cells carrying neurological disease-causing mutations in the TREM2 receptor differentiate normally and respond appropriately to pathogenic stimuli, despite the absence of functional TREM2 receptor on the plasma membrane.

Direct Conversion of Mouse Fibroblasts into Cholangiocyte Progenitor Cells

Thu, 03/29/2018 - 00:00
In this article, Han and colleagues revisited the roles of HepSC-specific factors and found that Hnf1α and Foxa3 facilitate the robust conversion into iHepSCs displaying a relatively closer transcriptional pattern with LEPCs. The prolonged in vitro culture of iHepSCs induces Notch-mediated secondary conversion into iCPCs, which could efficiently be differentiated into mature cholangiocytes.

Heterogeneity of Human Breast Stem and Progenitor Cells as Revealed by Transcriptional Profiling

Thu, 03/29/2018 - 00:00
In this article, Colacino and colleagues use flow-cytometry-sorted populations and single-cell analyses to investigate human mammary stem cells. They discover unexpected phenotypic and functional heterogeneity at the single-cell level, including a subpopulation of ALDH+ stem cells with a hybrid epithelial/mesenchymal phenotype and triple-negative breast cancer-like gene expression pattern.

Promoting Myelin Repair through In Vivo Neuroblast Reprogramming

Thu, 03/29/2018 - 00:00
Durbec and colleagues highlight the fate plasticity of neuroblasts in mouse brain after demyelination. They show that a subset of neuroblasts produced in SVZ spontaneously convert into oligodendrocytes after demyelination. They furthermore demonstrate that myelin regeneration can be enhanced by forcing this spontaneous conversion through in-vivo-directed cell reprogramming by forced expression of Olig2 and Sox10 in endogenous neuroblasts.

Far Upstream Element-Binding Protein 1 Regulates LSD1 Alternative Splicing to Promote Terminal Differentiation of Neural Progenitors

Thu, 03/29/2018 - 00:00
In this article, Paik and colleagues demonstrate that FUBP1 plays an indispensable role in promoting terminal differentiation of neurons and that lack of FUBP1 interferes with early-born neuronal cells exiting the cell cycle and predisposes these cells for transformation. These findings explain how FUBP1 serves uniquely as a tumor suppressor in the CNS.

A Critical Role of TET1/2 Proteins in Cell-Cycle Progression of Trophoblast Stem Cells

Thu, 03/22/2018 - 00:00
TET proteins are well known for their role in pluripotency. Here, Hemberger and colleagues show that TET1 and TET2 are also critical for maintaining the epithelial integrity of trophoblast stem cells. TET1/2 ensure mitotic cell-cycle progression by stabilizing cyclin B1 and by regulating centrosome organization. These insights reveal the importance of TET proteins beyond their role in epigenome remodeling.

Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development

Thu, 03/22/2018 - 00:00
Sances et al. combine Organ-Chip technology with human induced pluripotent stem cell-derived spinal motor neurons to study the maturation effects of Organ-Chip culture. By including microvascular cells also derived from the same patient line, the authors show enhancement of neuronal function, reproduction of vascular-neuron pathways, and specific gene activation that resembles in vivo spinal cord development.

A Humanized Mouse Model Generated Using Surplus Neonatal Tissue

Thu, 03/22/2018 - 00:00
Corresponding author William Burlingham and colleagues created a humanized mouse model called the NeoThy. The NeoThy uses human neonatal, rather than fetal, tissue sources for generating a human immune system within immunocompromised mouse hosts. NeoThy mice are an attractive alternative to conventional humanized mouse models, as they enable robust and reproducible iPSC immunogenicity experiments in vivo.

Retinal Ganglion Cell Diversity and Subtype Specification from Human Pluripotent Stem Cells

Thu, 03/22/2018 - 00:00
In this article, Langer and colleagues present extensive characterization of RGC subtypes derived from human pluripotent stem cells, with multiple subtypes identified by subtype-specific molecular markers. Their results present a more detailed analysis of RGC diversity in human cells and yield the use of different markers to identify RGC subtypes.

A Critical Role of TET1/2 Proteins in Cell-Cycle Progression of Trophoblast Stem Cells

Thu, 03/22/2018 - 00:00
TET proteins are well known for their role in pluripotency. Here, Hemberger and colleagues show that TET1 and TET2 are also critical for maintaining the epithelial integrity of trophoblast stem cells. TET1/2 ensure mitotic cell-cycle progression by stabilizing cyclin B1 and by regulating centrosome organization. These insights reveal the importance of TET proteins beyond their role in epigenome remodeling.

Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development

Thu, 03/22/2018 - 00:00
Sances et al. combine Organ-Chip technology with human induced pluripotent stem cell-derived spinal motor neurons to study the maturation effects of Organ-Chip culture. By including microvascular cells also derived from the same patient line, the authors show enhancement of neuronal function, reproduction of vascular-neuron pathways, and specific gene activation that resembles in vivo spinal cord development.

A Humanized Mouse Model Generated Using Surplus Neonatal Tissue

Thu, 03/22/2018 - 00:00
Corresponding author William Burlingham and colleagues created a humanized mouse model called the NeoThy. The NeoThy uses human neonatal, rather than fetal, tissue sources for generating a human immune system within immunocompromised mouse hosts. NeoThy mice are an attractive alternative to conventional humanized mouse models, as they enable robust and reproducible iPSC immunogenicity experiments in vivo.

Retinal Ganglion Cell Diversity and Subtype Specification from Human Pluripotent Stem Cells

Thu, 03/22/2018 - 00:00
In this article, Langer and colleagues present extensive characterization of RGC subtypes derived from human pluripotent stem cells, with multiple subtypes identified by subtype-specific molecular markers. Their results present a more detailed analysis of RGC diversity in human cells and yield the use of different markers to identify RGC subtypes.

CD73 Regulates Stemness and Epithelial-Mesenchymal Transition in Ovarian Cancer-Initiating Cells

Thu, 03/15/2018 - 00:00
Cavallaro et al. characterized the transcriptome of OCIC-enriched primary cultures and found CD73 as an upregulated gene. CD73 was then shown to regulate the expression of stemness and EMT-associated genes. The expression and function of CD73 in OCICs is required for tumor initiation, and CD73-targeted drugs decrease the rate of tumor take and inhibit cancer growth.

UTX Affects Neural Stem Cell Proliferation and Differentiation through PTEN Signaling

Thu, 03/15/2018 - 00:00
In this article, Jiao and colleagues show that UTX is a critical regulator of neural progenitor cell proliferation and neurogenesis. When Utx is suppressed, the generation of neurons and terminal mitosis are affected. This study states that UTX controls the development of embryonic cortex through Pten in a sex-specific manner.

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