Cell Stem Cell

TET2-mutant myeloid cells mitigate Alzheimer’s disease progression via CNS infiltration and enhanced phagocytosis in mice (Cell Stem Cell 32, 1285e1–e8; August 7, 2025)

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Hallmarks of totipotent and pluripotent stem cell states In this review, Peng Du and Jun Wu present a detailed overview of the growth conditions, molecular characteristics, and functional attributes of totipotent and pluripotent stem cells generated in vitr...

Research highlight from Cell Stem Cell: Hallmarks of totipotent and pluripotent stem cell states
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Hallmarks of cancer stemness Cancer stemness, regarded as a crucial factor in tumor development, has been recognized to involve a plastic cellular state influenced by dynamic interactions between cancer stem cells (CSCs) and thei...

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Comparative single-cell lineage tracing identifies distinct adipocyte precursor dynamics in skin and inguinal fat Morris and colleagues use single-cell lineage tracing to track adipocyte formation in mouse skin. They demonstrate that distinct precursor populations—progenitors and immature preadipocytes—exhibit different potentials for generating mature adipocytes, uncover depot-specific extrinsic regulation, and identify Sox9 as a key intrinsic regulator of skin adipogenesis.

Online Now! Comparative single-cell lineage tracing identifies distinct adipocyte precursor dynamics in skin and inguinal fat #stemcells

An unexpected potential benefit of blood stem cells Until now blood stem cell mutations have primarily been associated with promoting disease progression. This is the first time that these two mutations have been shown to influence disease in different...

Research by @thekinglab.bsky.social, K Matatall et al shows an unexpected potential benefit of #bloodStemCells #AlzheimersDisease @bcmhouston.bsky.social #TCHResearchNews #CAGTHouston @cp-cellstemcell.bsky.social blogs.bcm.edu/2025/07/15/f...

Chemical reprogramming of human blood cells to pluripotent stem cells Chemical reprogramming offers an innovative approach for cell fate manipulation. Here, Deng and colleagues developed a robust chemical reprogramming method to convert human blood cells to pluripotent stem cells.

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Parasympathetic neurons derived from human pluripotent stem cells model human diseases and development Wu et al. differentiate hPSC-derived Schwann cell precursors into functional parasympathetic neurons. These parasympathetic neurons are employed to study specific defects in the genetic autonomic diso...

Research highlight from Cell Stem Cell: Parasympathetic neurons derived from human pluripotent stem cells model human diseases and development
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The epidermal circadian clock integrates and subverts brain signals to guarantee skin homeostasis Circadian clocks are present throughout the body and act in a coordinated manner to maintain organismal health. By circadian profiling of isolated brain:epidermal clock communication, Mortimer and col...

Research highlight from Cell Stem Cell: The epidermal circadian clock integrates and subverts brain signals to guarantee skin homeostasis
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Activating innate immune responses repolarizes hPSC-derived CAR macrophages to improve anti-tumor activity Chimeric antigen receptor macrophages (CAR-Ms) hold new prospects for cancer immunotherapy. Here, by focusing on efficiency and function, Shen et al. establish feasible methodologies that significantl...

Research highlight from Cell Stem Cell: Activating innate immune responses repolarizes hPSC-derived CAR macrophages to improve anti-tumor activity
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Harnessing developmental dynamics of spinal cord extracellular matrix improves regenerative potential of spinal cord organoids Neonatal spinal cord exhibits impressive regenerative capabilities after injury. Sun et al. demonstrate that the neonatal spinal cord extracellular matrix creates a developmental microenvironment for ...

Research highlight from Cell Stem Cell: Harnessing developmental dynamics of spinal cord extracellular matrix improves regenerative potential of spinal cord organoids
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Human anti-PSCA CAR macrophages possess potent antitumor activity against pancreatic cancer Yu and colleagues demonstrated that CAR macrophages derived from human induced pluripotent stem cells offer potential as an alternative to CAR-T cells for treating solid tumors. The allogeneic CAR mac...

Research highlight from Cell Stem Cell: Human anti-PSCA CAR macrophages possess potent antitumor activity against pancreatic cancer
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Modeling blood-brain barrier formation and cerebral cavernous malformations in human PSC-derived organoids Guo and colleagues created human blood-brain barrier (hBBB) assembloids using stem cell-derived brain and blood vessel organoids. These models mimic key blood-brain barrier (BBB) characteristics and r...

Research highlight from Cell Stem Cell: Modeling blood-brain barrier formation and cerebral cavernous malformations in human PSC-derived organoids
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Non-canonical functions of DNMT3A in hematopoietic stem cells regulate telomerase activity and genome integrity Challen and colleagues show that the clonal expansion of Dnmt3a-null HSCs in serial bone marrow transplantation assays is not dependent on the loss of DNA methylation functions of Dnmt3a. They identify non-canonical functions for Dnmt3a in the regulation of telomere length and genome stability that restrict the functional potential of HSCs.

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Cell Stem Cell papers are available for full download 12 months after publication

Explore a collection of articles highlighting recent advancements in gene editing, viral vector delivery, and bioengineering techniques that are accelerating the development of gene and cell-based therapies: www.cell.com/cp/collectio...

Bacterial ADP-heptose triggers stem cell regeneration in the intestinal epithelium following injury Here, Goyal et al. identify that the ALPK1-TIFA innate immune signaling pathway regulates regeneration in the intestinal epithelium. Importantly, detection of ADP-heptose by ALPK1 triggers intestinal stem cell death and the de-differentiation of Paneth cells to reestablish the intestinal stem cell pool.

Online Now! Bacterial ADP-heptose triggers stem cell regeneration in the intestinal epithelium following injury #stemcells

Toward building kidney organoids with plumbing: Fusion of nephron with ureteric bud The fusion of distal nephron and ureteric bud represents a critical developmental milestone required for establishing a functional kidney plumbing system. In this issue of Cell Stem Cell, Shi et al. report a protocol for generating human kidney organoids with an integrated collecting system by recapitulating this key developmental fusion event.

Toward building kidney organoids with plumbing: Fusion of nephron with ureteric bud

The future belongs to those who believe in multiplex CAR T engineering Toxicity and immune evasion have hindered the success of CAR T cells in HER2-positive solid tumors. In this issue of Cell Stem Cell, Hosking et al. present an iPSC-derived CAR T cell product engineered for tumor-selective targeting, resistance to the immunosuppressive tumor microenvironment, enhanced persistence and trafficking, and mitigation of antigen escape.

The future belongs to those who believe in multiplex CAR T engineering

Beyond transplantation: Gene-edited pig liver supports function in a human host A recent study in Nature demonstrates that a gene-edited pig liver can function in a brain-dead human for short-term support. This highlights the potential of xenogeneic liver transplantation as bridge therapy and opens new directions in regenerative medicine and cross-species organ engineering.

Beyond transplantation: Gene-edited pig liver supports function in a human host

Submit abstract here

We’re delighted to welcome Future Science Prize 2024 winner Hongkui Deng @pku1898.bsky.social to the speaker lineup at the upcoming @CellSymposia #CSStemCells2025. Submit an abstract for a chance to join him in LA in November! http://dlvr.it/TLn6Xg

From symbiote to bad neighbor: The intestinal microbiome as a driver of CHIP Hematopoietic stem cells (HSCs) with mutations that can cause clonal hematopoiesis of indeterminate potential (CHIP) accumulate during aging. Agarwal et al. demonstrate in Nature that intestinal barrier permeability increases with age and enables the microbial metabolite ADP-Heptose to reach the bone marrow, thus driving the expansion of DNMT3A-mutant HSCs.

From symbiote to bad neighbor: The intestinal microbiome as a driver of CHIP

Hallmarks of stem cell aging Aging disrupts core functions of somatic stem cells throughout the body, leading to impaired tissue maintenance and repair. We identify five key features of aged stem cells, highlighting how their dysfunction contributes to aging phenotypes and offering a framework for targeting stem cell decline to preserve tissue health.

Hallmarks of stem cell aging

An organ-chip model of sporadic ALS using iPSC-derived spinal cord motor neurons and an integrated blood-brain-like barrier Lall et al. differentiate iPSCs from young-onset, sporadic ALS patients into spinal cord motor neurons and co-culture them with brain microvascular endothelial-like cells in a microfluidic organ-chip system. Transcriptomics, proteomics, and single-nuclei RNA sequencing identify distinct motor neuron subpopulations with ALS-specific dysregulation in neurofilaments, glutamatergic, and synaptic signaling.

An organ-chip model of sporadic ALS using iPSC-derived spinal cord motor neurons and an integrated blood-brain-like barrier

To play Paneth or goblet: Shapeshifting secretory cells read the room (Cell Stem Cell 32, 861–863; June 5, 2025)

To play Paneth or goblet: Shapeshifting secretory cells read the room

Multiomic profiling reveals that prostaglandin E2 reverses aged muscle stem cell dysfunction, leading to increased regeneration and strength Wang et al. uncover that aged muscle stem cells have blunted PGE2-EP4 signaling that is critical for their regenerative function. Treatment with exogenous PGE2 reverses age-related defects in muscle stem cells and imparts an epigenetic response that enhances their capacity for repair after injury and transplantation.

Multiomic profiling reveals that prostaglandin E2 reverses aged muscle stem cell dysfunction, leading to increased regeneration and strength

Human airway submucosal gland organoids to study respiratory inflammation and infection Lin and Pou Casellas et al. established human airway submucosal gland (SMG) organoid cultures that capture region-specific mucous cells and viral infection responses. These SMG organoids provide a new platform to investigate airway regeneration, inflammation, and viral infections, offering insights into respiratory (patho-)physiology beyond the surface epithelium.

Human airway submucosal gland organoids to study respiratory inflammation and infection

Preferential tumor targeting of HER2 by iPSC-derived CAR T cells engineered to overcome multiple barriers to solid tumor efficacy Hosking and colleagues have generated and preclinically characterized an off-the-shelf, allogeneic CAR T cell, derived from an induced pluripotent stem cell, that is intended to target HER2 on cancer cells without harming HER2-expressing healthy cells. Additional genetic edits have been specifically introduced to improve and sustain activity within solid tumors.

Preferential tumor targeting of HER2 by iPSC-derived CAR T cells engineered to overcome multiple barriers to solid tumor efficacy

IGF2BP1 restricts the induction of human primordial germ cell fate in an m6A-dependent manner Zhang, Gu, Tong, et al. use human primordial germ cell-like cells induced from ESCs to show that germline entry is restricted via epitranscriptomic regulation of OTX2 by the m6A reader IGF2BP1. They demonstrate that an m6A-IGF2BP1-OTX2-MacroH2A.1-TFAP2C axis is essential to regulate human germ cell fate.

IGF2BP1 restricts the induction of human primordial germ cell fate in an m6A-dependent manner

Deconvoluting clonal and cellular architecture in IDH-mutant acute myeloid leukemia Sirenko et al. profile IDH1/2-mutated AML patients across disease stages (diagnosis, remission, and relapse) and treatments (targeted IDH inhibitors, chemotherapy, and hypomethylating agents). They delineate transcriptional programs associated with co-mutations (NPM1, SRSF2, and NRAS), treatment response, and relapse. Single-cell mutation tracking reveals the selection of rare diagnosis clones at relapse.

Deconvoluting clonal and cellular architecture in IDH-mutant acute myeloid leukemia

Establishing dorsal-ventral patterning in human neural tube organoids with synthetic organizers Luo et al. developed a method to generate dorsal-ventral (D-V) patterned neural tube organoids (NTOs) from both zebrafish and human pluripotent stem cells (hPSCs) by engineering opposing BMP and SHH signaling centers. The human NTOs recapitulate the full complement of 13 neural progenitor subtypes arranged along the D-V axis, with transcriptomic profiling revealing high similarity to the human embryonic spinal cord at Carnegie stage 12.

Establishing dorsal-ventral patterning in human neural tube organoids with synthetic organizers