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Totani, Matsumura et al. characterize a subpopulation of aged hematopoietic stem cells with high mitochondrial mass and GPR183 expression that retain high regenerative potential, gain a selective survival advantage and maintain self-renewal capacity, emphasizing their adaptive importance.

Analysis of the blood DNA virome in patients with COVID-19 and autoimmune disease associates endogenous HHV-6 (eHHV-6) and high anellovirus load with increased disease risk, most notably for systemic lupus erythematosus. eHHV-6 carriers show a distinct immune response.

This study introduces a label-free imaging and machine learning platform that predicts hematopoietic stem cell function based on their dynamic behaviors, offering new insights into stem cell diversity and potential clinical applications.

In fetal liver, the structure of the differentiated haemapoietic progenitor cell population is established directly from precursor cells, independently of haemapoietic stem cells.

Ketogenesis is critical for survival during the neonatal and perinatal periods. Arima et al. determine that hepatic ketogenesis prevents hyperacetylation of mitochondrial proteins and disruption of mitochondrial energetics.

Although type I interferons such as interferon-α are well known to protect against viral infection, they may have other physiological effects in the uninfected state. Taku Sato et al. now show that type I interferon signaling in hematopoietic stem cells promotes their proliferation and impairs their ability to reconstitute the hematopoietic system (pages 696–700).

The transcription factor MYB has been shown to regulate haematopoietic stem cells but there could be lineage specific enhancers. Here, using lineage tracing and single cell sequencing the authors characterise a Myb −68 enhancer that regulates the differentiation of mast cells and basophils.

When double-strand breaks occur in eukaryotic DNA, the chromatin that protects and organizes the genome must be removed from the vicinity of the break to allow repair factors to bind. Such chromatin displacement involves the addition of ubiquitin groups to histone proteins near the break by the ubiquitin ligases RNF8 and RNF168. Here it is shown that the enzyme OTUB1 prevents RNF168-dependent poly-ubiquitination. Pharmacological targeting of this process might enhance the DNA damage response.

Autoimmune pulmonary alveolar proteinosis (aPAP) is a complex lung disease caused by abnormal surfactant homeostasis. Here, the authors carry out a genome-wide association study of aPAP in a Japanese cohort, finding variants in the MHC and suggesting predisposition to abnormal antibody production.

Studies of mouse models and advances in metabolomic analysis, particularly of haematopoietic stem cells, have revealed how metabolic cues from anaerobic glycolysis, bioenergetic signalling, the AKT–mTOR pathway, and Gln and fatty acid metabolism, affect the balance between stem cell self-renewal and differentiation. Understanding how metabolic pathways regulate fate decisions may be beneficial therapeutically.

PD-1 and PD-L1 are important immune checkpoint molecules that modulate T cell activity. A study now shows that PD-1 marks leukaemia stem cells (LSCs) in T cell acute lymphoblastic leukaemia and reveals therapeutic opportunities to target LSCs via anti-PD-1 therapy.

Repeated cell divisions induce DNA damage in haematopoietic stem cells (HSC) and telomeres are sensitive to this damage. Here, the authors show in murine HSCs that the telomere binding protein POT1a inhibited the production of reactive oxygen species, and rejuvenated aged HSCs.

Yuji Okuno et al. find that pathological angiogenesis in mice requires dampening of oxidative stress. In the absence of the ATM protein kinase, increased oxidative stress leads to activation of the p38α protein kinase and inhibition of new blood vessel growth. These findings run counter to the commonly held concept that decreasing oxidative stress would inhibit pathological angiogenesis and suggest new targets for treating diseases involving abnormal blood vessel growth.

Keisuke Ito et al. uncover a new pathway regulating hematopoietic stem cell maintenance and function. In this pathway, the promyelocytic leukemia protein (PML) regulates the activity of the PPAR-δ nuclear hormone receptor and, thereby, fatty acid oxidation, such that PPAR-δ activators have the potential of improving stem cell function. Intriguingly, this pathway controls the cell fate of dividing stem cells.

Damaged mitochondria are targeted for mitophagy by the Pink–Parkin ubiquitin pathway. The mitochondrial ATPase Atad3a prevents aberrant activation of Pink and protects hematopoietic stem cells.

PRMT arginine methyltransferases mediate post-translational modification. Takayanagi and colleagues show that a lack of PRMT5 in cells of the T cell lineage compromises their response to cytokines dependent on the common γ-chain, due to aberrant splicing of mRNA transcripts encoding the common γ-chain and its associated kinase JAK3.

This Consensus Statement provides a nomenclature framework and experimental recommendations for studying mitochondrial transfer and transplantation.

Notch signalling has a key role in the generation of haematopoietic stem cells (HSCs) during vertebrate development; here two adhesion molecules, Jam1a and Jam2a, are shown to be essential for the contact between precursors of HSCs and the somite during embryonic migration, and the Jam1a–Jam2a interaction is shown to be needed to transmit the Notch signal and produce HSCs.

Identification of a transmembrane protein, Mfsd2b, that is essential for the export of the signalling molecule sphingosine-1-phosphate (S1P) from red blood cells and platelets.

A total of 1074 patients with a history of ischemic stroke enrolled in The Recurrent Stroke Prevention Clinical Outcome (RESPECT) Study were assigned to intensive blood pressure (BP) control group (blood pressure < 120/80 mmHg) or standard blood pressure control group (blood pressure < 140/90 mmHg) and were followed up for a mean of 3.9 years. Seventy-eight first recurrent strokes occurred, including 70 ischemic stroke and 8 intracerebral hemorrhage. Intensive treatment did not change annual risk of ischemic stroke (1.74% vs. 1.75%, P = 0.999), but markedly reduced risk of hemorrhagic stroke (0.00% vs. 0.39%, P = 0.005). Beneficial effect of intensive BP control were observed for risk of hemorrhagic stroke in the patients with a history of ischemic stroke.

An intravital imaging method reveals the in vivo motile dynamics and colonization process of neonatal hematopoietic stem cells during bone marrow formation.