Engineering Human Bone Marrow Proxies

Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Author(s): Paul E. Bourgine, Ivan Martin, Timm Schroeder
Recent advances in engineering complex organs in vitro inspire the development of human bone marrow equivalents to foster scientific discovery and innovative therapeutics. Here, we discuss challenges in generating relevant human bone marrow proxies, potential design principles, and future directions.

Teaser

Recent advances in engineering complex organs in vitro inspire the development of human bone marrow equivalents to foster scientific discovery and innovative therapeutics. Here, we discuss challenges in generating relevant human bone marrow proxies, potential design principles, and future directions.


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Who Defends the Stem Cell’s Citadel?

Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Author(s): Hélène Strick-Marchand, David Durantel
Recently in Cell, Wu et al. (2018) demonstrated that intrinsic expression of a subset of interferon stimulated genes confers resistance to viral infections in stem cells both in vitro and in vivo, while differentiated cells lose this intrinsic gatekeeper expression pattern in favor of inducible interferon responses.

Teaser

Recently in Cell, Wu et al. (2018) demonstrated that intrinsic expression of a subset of interferon stimulated genes confers resistance to viral infections in stem cells both in vitro and in vivo, while differentiated cells lose this intrinsic gatekeeper expression pattern in favor of inducible interferon responses.


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De Novo DNA Methylation: Marking the Path from Stem Cell to Neural Fate

Publication date: 5 April 2018
Source:Cell Stem Cell, Volume 22, Issue 4
Author(s): Ayana Sawai, Jeremy S. Dasen
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.

Teaser

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.


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Engineering Stem and Stromal Cell Therapies for Musculoskeletal Tissue Repair

Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3
Author(s): Claudia Loebel, Jason A. Burdick
Stem cells and tissue-derived stromal cells stimulate the repair of degenerated and injured tissues, motivating a growing number of cell-based interventions in the musculoskeletal field. Recent investigations have indicated that these cells are critical for their trophic and immunomodulatory role in controlling endogenous cells. This Review presents recent clinical advances where stem cells and stromal cells have been used to stimulate musculoskeletal tissue repair, including delivery strategies to improve cell viability and retention. Emerging bioengineering strategies are highlighted, particularly toward the development of biomaterials for capturing aspects of the native tissue environment, altering the healing niche, and recruiting endogenous cells.

Teaser

Loebel and Burdick highlight emerging bioengineering strategies using stem and stromal cells for musculoskeletal tissue repair, particularly focusing on the development of biomaterials for capturing aspects of the native tissue environment, altering the healing niche, and recruiting endogenous cells.


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Submucosal Gland Myoepithelial Cells Are Reserve Stem Cells That Can Regenerate Mouse Tracheal Epithelium

Publication date: Available online 12 April 2018
Source:Cell Stem Cell
Author(s): Thomas J. Lynch, Preston J. Anderson, Pavana G. Rotti, Scott R. Tyler, Adrianne K. Crooke, Soon H. Choi, Daniel T. Montoro, Carolyn L. Silverman, Weam Shahin, Rui Zhao, Chandler W. Jensen-Cody, Andrea Adamcakova-Dodd, T. Idil Apak Evans, Weiliang Xie, Yulong Zhang, Hongmei Mou, B. Paul Herring, Peter S. Thorne, Jayaraj Rajagopal, Charles Yeaman, Kalpaj R. Parekh, John F. Engelhardt
The mouse trachea is thought to contain two distinct stem cell compartments that contribute to airway repair—basal cells in the surface airway epithelium (SAE) and an unknown submucosal gland (SMG) cell type. Whether a lineage relationship exists between these two stem cell compartments remains unclear. Using lineage tracing of glandular myoepithelial cells (MECs), we demonstrate that MECs can give rise to seven cell types of the SAE and SMGs following severe airway injury. MECs progressively adopted a basal cell phenotype on the SAE and established lasting progenitors capable of further regeneration following reinjury. MECs activate Wnt-regulated transcription factors (Lef-1/TCF7) following injury and Lef-1 induction in cultured MECs promoted transition to a basal cell phenotype. Surprisingly, dose-dependent MEC conditional activation of Lef-1 in vivo promoted self-limited airway regeneration in the absence of injury. Thus, modulating the Lef-1 transcriptional program in MEC-derived progenitors may have regenerative medicine applications for lung diseases.

Graphical abstract

Teaser

Following severe injury to the surface airway epithelium (SAE), Wnt signals activate myoepithelial cells in the submucosal glands (SMGs) to function as reserve stem cells for multipotent basal cells in the SAE and other SMG cell types. Lef-1 activation induces the myoepithelial cell regenerative response and a basal cell-like phenotype.


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Mentoring the Next Generation: Robert Langer

Publication date: 1 March 2018
Source:Cell Stem Cell, Volume 22, Issue 3

Mentor-mentee relationships are essential for professional development, but developing these interpersonal skills is not often highlighted as a priority in scientific endeavors. In a yearlong series, Cell Stem Cell interviews prominent scientists who have prioritized mentorship over the years. Here, we chat with Dr. Robert Langer about his views.

Teaser

Mentor-mentee relationships are essential for professional development, but developing these interpersonal skills is not often highlighted as a priority in scientific endeavors. In a yearlong series, Cell Stem Cell interviews prominent scientists who have prioritized mentorship over the years. Here, we chat with Dr. Robert Langer about his views.


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The Rules of Successful Speed Dating Are Complex, Even for Super-Enhancers

Publication date: 5 April 2018
Source:Cell Stem Cell, Volume 22, Issue 4
Author(s): Raymond Poot
Super-enhancers (SEs) are important for regulating cell identity genes and oncogenes, but correctly assigning target genes to SEs is difficult. Recently in Cell Reports, Lopes Novo et al. (2018) map interactions between SEs and promoters and observe a significant rewiring of complex SE-promoter networks between different pluripotent states.

Teaser

Super-enhancers (SEs) are important for regulating cell identity genes and oncogenes, but correctly assigning target genes to SEs is difficult. Recently in Cell Reports, Lopes Novo et al. (2018) map interactions between SEs and promoters and observe a significant rewiring of complex SE-promoter networks between different pluripotent states.


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