Studies from Ionescu et al.1 and Clayton et al.2 using multiple sclerosis (MS) patient-derived cell models underscore cholesterol metabolism’s role in inflammatory and dysfunctional cell phenotypes in the disease. Inhibiting cholesterol biosynthesis ameliorated critical cellular phenotypes, emphasizing the need to further investigate this pathway as a potential target for MS treatment.

Two recent publications in Cell Stem Cell, Yang et al.1 and Migliorini et al.,2 utilized pluripotent stem cell-derived co-culture systems to explore the role of macrophages within the pancreatic islet during development and disease states.

An inappropriate induction of trained immunity in the bone marrow progenitors of immune cells has been described to underlie chronic inflammatory processes. Mills and colleagues’ recently published paper in Cell Stem Cell shows that maladaptive trained immunity drives inflammation in autoimmune processes,1 opening a new area of research in autoimmunity.

Epitope editing is a promising strategy for protecting hematopoietic cells from eradication by immunotherapies. Recently, in Cell Stem Cell, Ji et al. applied both base editing (BE) and prime editing (PE) to alter the epitope of CD123 in hematopoietic stem cells for CAR-T therapy against acute myeloid leukemia.1

The Dutch Health Council has advised to extend the 14-day rule to 28 days and to subsume integrated stem cell-based embryo models under the same legislative regime as natural embryos. Public discussion is necessary due to the ethical issues that may emerge from studying integrated and non-integrated embryo models.

Neurodevelopment involves the migration, projection, and integration of various cell types across different regions of the nervous system. Assembloids are self-organizing systems formed by the integration of multiple organoids or cell types. Here, we outline the generation and application of assembloids. We illustrate how assembloids recapitulate critical neurodevelopmental steps, like migration, axon

Download: Download high-res image (353KB) Download: Download full-size image Charles K.F. ChanChuck Chan dedicated his life to unraveling the mysteries of bone marrow niches and was the first to define and characterize a mouse and human skeletal stem cell lineage (SSC) tree. He was a brilliant scientist whose pioneering work in stem cell research has left an indelible mark on the field. His journey

In this issue of Cell Stem Cell, Siriwardena et al. analyze peri- and post-implantation marmoset trophoblast development in detail and establish marmoset trophoblast stem cell (TSC) lines from pluripotent stem cells (PSCs). Comparative analysis of marmoset and human TSCs provides insights into species-specific implantation and placentation strategies.

Drug sensitivity profiling in patient-derived tumor models offers new hope for improving outcomes in cancers lacking effective therapies. Al Shihabi et al.1 demonstrate that short-term cultures from bone and soft tissue sarcomas enable clinically meaningful screening of multiple drugs and combinations, marking a significant advance in personalized care for these high-risk diseases.

The rapid proliferation of businesses engaged in direct-to-consumer advertising of unproven stem cell interventions has raised troubling questions about whether government bodies can regulate this health market effectively. Recent developments in Australia and Canada suggest that such fears are unfounded and that targeted regulatory action can have meaningful effects.

The use of stem cells to model the early human embryo promises to transform our understanding of developmental biology and human reproduction. In this review, we present our current knowledge of the first 2 weeks of human embryo development. We first focus on the distinct cell lineages of the embryo and the derivation of stem cell lines. We then discuss the intercellular crosstalk that guides early

(Cell Stem Cell 21, 547–555.e1–e7; October 5, 2017)

(Cell Stem Cell 19, 326–340; September 1, 2016)

CD54 and CD58 are adhesion proteins that mediate efficient immune synapse formation. Hammer et al. now show that the abrogation of these molecules in T and NK cells prevents their immune rejection while maintaining their effector function. These findings should significantly help advance our efforts to generate “off-the-shelf” allogeneic products.

While the placenta regulates nutritional exchange between mother and fetus, Yu et al. reveal that human placental development is itself nutrient-sensitive. They elucidate entwined metabolic and epigenetic transitions driving syncytialization and pinpoint a requirement for the metabolite acetyl-CoA, which is sensitive to glucose metabolism.

Regeneration is a persistent process that restores tissue architecture and function in the face of day-to-day cell loss or the aftershock of injury. Capacities and mechanisms for regeneration can vary widely among species, organs, and injury contexts. Here, we describe “hallmarks” of regeneration found in diverse settings of the animal kingdom, including activation of a cell source, initiation of regenerative

Macrophages regulate angiogenesis, repair, conduction, and homeostasis in heart tissue. Landau et al.1 demonstrate that incorporating primitive macrophages into engineered heart tissues significantly promotes long-term vascularization and cardiac maturation. This advance demonstrates the importance of resident immune-vascular microenvironments in cardiac tissue engineering, marking an important step

Mitrofanova et al.1 engineer a human colonic in vitro model capable of producing an intestinal mucus barrier, with potential applications for predicting drug-induced gastrointestinal toxicity. This improved system paves the way for more accurate and efficient drug development processes.

Morphogen gradients are critical regulators of embryonic development. In this issue, Liu et al.1 introduce a microfluidic system that externally applies morphogen gradients to an in vitro model of human embryo segmentation. It enables the investigation of signaling gradients during this developmental process at unprecedented levels of precision.

Yang et al.1 generate tissue engineered blood vessels from hiPSC-derived smooth muscle cells harboring a mutation found in Loeys-Dietz syndrome. In vitro and in vivo data from these vessels provide new insight into the molecular physiology of aortic aneurysms and may create a paradigm for understanding a suite of vascular diseases.

Tissue regeneration after damage is generally thought to involve the mobilization of adult stem cells that divide and differentiate into progressively specialized progeny. However, recent studies indicate that tissue regeneration can be accompanied by reversion to a fetal-like state. During this process, cells at the injury site reactivate programs that operate during fetal development but are typically

Induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) therapy has emerged as a highly promising field of heart repair. Lin et al.1 presented compelling evidence on the long-term engraftment and maturation of autologous iPSC-CMs in two rhesus macaques, demonstrating unprecedented cardiac autografting data in large animal models without the need of immunosuppressants.

The differentiation trajectories defining enteroendocrine (EE) cell heterogeneity remain obscure. In this issue of Cell Stem Cell, Singh et al.1 map the differentiation landscape of EE cells, identifying early oscillating cell progenitor states, which play a critical role in generating terminal EE cell diversity.