How do we protect the heart during chemotherapy with the anthracycline drug class? Tackling this question, Liu et al. combined pluripotent stem cell models, CRISPR genetic screens, and molecular modeling to identify indisulam as a potential cardioprotective drug in this issue of Cell Stem Cell.

Species-specific differences motivate the development of human hematopoiesis models. Georgescu et al.1 present a microfluidic model of the human bone marrow perivascular niche to capture innate immune cell mobilization. Automated cultivation and high-content analysis for robust insights enabled studies of radiation injury and chemotherapy dosing.

In this issue of Cell Stem Cell, Shen et al. investigate in vivo transient expression of Yamanaka factors (YFs) during embryogenesis and an adult mouse model of Alzheimer’s disease (AD)-associated amyloidosis. These studies demonstrate that transient induction of YFs may be capable of enhancing neurogenesis and offer resilience against neurodegeneration.

In this issue of Cell Stem Cell, Mou et al. identified a brain-bone marrow axis reinforcing myelopoiesis and neuroinflammation during psychological stress, culminating in depression. The identification of this pathway provides insights into hematopoietic stem cell homeostasis and regulatory neuronal function with potentially significant implications for the treatment of stress-related disorders.

Morphogens orchestrate cellular diversity during nervous system development, yet a systematic approach to harnessing these signals in stem cell differentiation remains elusive. Amin et al.1 present a platform integrating parallel morphogen modulator screening with single-cell sequencing of neural organoids, reinforcing brain regionalization principles and enabling detailed cellular annotation.

Recently in Cell, Wang and colleagues1 report the functional cure of a patient with type 1 diabetes after transplantation of autologous, induced pluripotent stem cell (iPSC)-derived islets in the rectus abdominis muscle.

After many years of little progress, there is now hope for improved in vitro production of hematopoietic stem cells (HSCs). Ng et al.1 have developed defined conditions that allow the generation of HSCs from induced pluripotent stem cells (iPSCs) with unprecedented blood-repopulating capacity.

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

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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.