(Cell Stem Cell 29, 1459–1474.e1–e9; October 6, 2022)

Glucose serves as an essential energy source for cells. In this issue, Lopez-Pajares et al.1 uncover a role for glucose uncoupled from its energetic function. During epidermal differentiation, free glucose accumulates and binds the pro-differentiation transcription factor IRF6, promoting its dimerization and DNA binding to activate genes that drive differentiation.

Metabolic regulation of embryonic development is increasingly recognized. Villaronga-Luque et al.1 and Stapornwongkul et al.2 show that metabolic activity influences gastruloid formation from mouse embryonic stem cells, revealing that the balance between glycolysis and oxidative phosphorylation regulates cell fate decisions during gastruloid self-organization.

The ability to transplant immunologically foreign cells into an animal without immune suppression would be transformative. Pavan et al. show that human pluripotent stem cell-derived dopaminergic neuron progenitors engineered to express eight immune-evasive proteins can engraft in humanized mice and a rat model of Parkinson’s disease without recourse to immune suppression.1

Yavitt et al.1 introduce a photodegradable hydrogel platform to control crypt curvature in intestinal organoids, revealing how epithelial morphology directs Paneth cell localization. This innovative approach advances organoid engineering, providing a reproducible method to study stem cell niche interactions and model intestinal development and disease.

Download: Download high-res image (228KB) Download: Download full-size image Roger A. Pedersen

Financial dispositions against unapproved stem cell interventions have grown significantly, with successful class-action lawsuits, malpractice claims, and collaborative prosecutions between government agencies. In addition to improved dispositions, federal circuit courts have given unanimous affirmation to the FDA’s regulatory authority over stem cell interventions, establishing critical precedents

Neural organoids have been utilized to recapitulate different aspects of the developing nervous system. While hailed as promising experimental tools for studying human neural development and neuropathology, current neural organoids do not fully recapitulate the anatomy or microcircuitry-level functionality of the developing brain, spinal cord, or peripheral nervous system. In this review, we discuss

(Cell Stem Cell 13, 459–470; October 3, 2013)

(Cell Stem Cell 31, 1003–1019.e1–e9; July 5, 2024)

Rodriguez-Fraticelli and colleagues combine genetic barcoding with ex vivo expansion and sister-cell analysis of murine hematopoietic stem cells (HSCs) carrying inducible leukemia driver mutations. This approach allows them to capture the intrinsic heterogeneity of clonal cell behaviors and study how these impact cell fates upon acquisition of leukemia driver mutations.

Human intestinal organoids (HIOs) generated from induced pluripotent stem cells (iPSCs) are utilized for disease modeling but they lack a full complement of niche components. Childs et al.1 demonstrate that EPIREGULIN-driven HIOs mature into functional, neuromuscular, and vascularized niches, establishing a powerful platform for human gut physiology and disease research.

Wagoner et al.1 use human tonsil organoids to uncover key immune mechanisms driving influenza vaccine responses. They identify Th1 cell frequencies as a critical predictor of neutralizing antibody responses to inactivated vaccines, providing new insights into vaccine effectiveness and paving the way for more targeted vaccine development in the future.

Researchers have demonstrated that a stem cell-derived heart muscle patch can safely remuscularize failing hearts.1 Published in Nature, the study shows successful long-term cardiac integration of a patch in a primate model and a human patient with no adverse effects. This breakthrough marks a major step toward regenerative therapies for advanced heart failure.

Human pluripotent stem cell (hPSC)-based therapies offer promise but pose potential risks due to culture-acquired genetic variants, some of which have been linked with cancer. An international workshop addressed these concerns, highlighting the need for improved strategies to stratify variants and chart a path toward definitive guidelines in hPSC-based therapy.

The new era of cell therapeutics has started with autologous products to avoid immune rejection. However, therapeutics derived from allogeneic cells could be scaled and made available for a much larger patient population if immune rejection could reliably be overcome. In this review, we outline gene engineering concepts aimed at generating immune-evasive cells. First, we summarize the current state

(Cell Stem Cell 29, 1181–1196.e1–e6; August 4, 2022)

Genomic imprinting ensures parent-of-origin gene expression and prevents uniparental development. In this issue of Cell Stem Cell, Li et al.1 extensively engineered androgenic haploid embryonic stem cells to overcome imprinting barriers, producing adult bi-paternal mice, albeit with low efficiency, and providing insights into roles of imprinted genes in development.

In a recent publication in Cell Stem Cell, Hong et al.1 uncovered paraspeckle component 1 (PSPC1) as a determinant of leukemogenic characteristics in acute myeloid leukemia (AML). PSPC1 is not essential for normal hematopoiesis but it is upregulated to interact with PU.1 to promote AML progression and is also emerging as a therapeutic target.

Evolution of the human brain involved neuron and glial cell changes. In this issue of Cell Stem Cell, Ciuba et al.1 identify an epigenetic mechanism central in the evolution of human astrocytes, where small enhancer modifications increased transcription factor binding, orchestrating transcriptomic changes that influence astrocyte structure and function.

In 2020, a case report described autologous transplantation of iPSC-derived dopamine (DA) neurons in a Parkinson’s disease (PD) patient.1 The team now follows up with the pre-clinical safety and efficacy data of autologous iPSC-derived DA neurons, forming the basis for regulatory approval of a phase 1 clinical trial involving 8 patients.2

The mechanisms underlying cognitive impairment in epilepsy remain poorly understood. Ammothumkandy et al.1 reveal that the loss of adult immature neurons correlates with auditory verbal learning deficits in human mesial temporal lobe epilepsy during a critical disease period, underscoring the pivotal role of adult neurogenesis in specific cognitive domain.

The maternal gut microbiota undergoes significant changes during pregnancy and plays a pivotal role in offspring development. In this issue, Dang et al. demonstrate that modifying the maternal gut microbiome during pregnancy shapes offspring neural and intestinal stem cells via the mTOR pathway, with long-lasting effects on their functions.

In this issue of Cell Stem Cell, Pan et al. generated human induced pluripotent stem cell (iPSC)-derived venous endothelial cells (iVECs) by manipulating cell-cycle dynamics and Notch signaling and demonstrated that TIE2-mutant iVECs recapitulate the pathogenesis of venous malformations.1 Their study provides a model for further mechanistic studies and drug discovery.

In this issue of Cell Stem Cell, two complementary studies from Zeng et al.1 and Demirci et al.2 improve the efficacy of gene therapy for β-hemoglobinopathies using multiplex CRISPR-Cas9 editing. The authors also optimize editing and conditioning protocols to reduce risks associated with current gene therapy procedures.

(Cell Stem Cell 30, 1452–1471.e1–e10; November 2, 2023)

(Cell Stem Cell 32, 10–37; January 2, 2025)