ArticleBlood2024
Adaptation to ex vivo culture reduces human hematopoietic stem cell activity independently of the cell cycle.
Article in Blood, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed.
- Severe inflammation and lineage skewing are associated with poor engraftment of engineered hematopoietic stem cells in patients with sickle cell disease.Nature communications · 2025Trial
- Activated protein C promotes hematopoietic stem and progenitor cell quiescence and engraftment.EMBO molecular medicine · 2026Article
- Suppressing glutamate dehydrogenase guides hematopoietic stem cell divisions into self-renewal.Nature communications · 2026Article
- Tgfbr3 is required for the long-term maintenance of self-renewal potential in murine hematopoietic stem cells.Blood science (Baltimore, Md.) · 2026Article
- Ex vivo expansion of hematopoietic stem and progenitor cells from human mobilized peripheral blood for gene therapy applications.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Parvovirus B19 targets hematopoietic stem cells to disrupt multilineage differentiation and drive pancytopenia.Cell death and differentiation · 2026Article
- A microgel bone marrow model of mesenchymal stromal cell paracrine signaling supporting hematopoietic stem cell retention.Acta biomaterialia · 2026Article
- Inhibition of inflammation and senescence with azole compound C7 enables expansion of hematopoietic stem and progenitor cells.Stem cells translational medicine · 2026Article
- ATP2B1 expression identifies human hematopoietic stem cells with superior repopulation and self-renewal.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Unlocking the HOX: Homeobox Genes as Regulators of Hematopoietic Development.International journal of molecular sciences · 2026Review
- Human TET2-Mutant Clonal Hematopoiesis Expansion Is Driven by Distinct Inflammatory Signaling Responses in Stem Cells Versus Myeloid Progeny.Blood cancer discovery · 2026Article
- Mesenchymal stromal cells modulate survival and regeneration of human hematopoietic stem cells via PGE2/cAMP signaling.Cell death & disease · 2026Article
- Ex vivo long-term expansion of human hematopoietic stem and progenitor cells as a tool for modeling vector integration sites and clonality.Journal of translational medicine · 2026Article
- Nanoengineered 3D culture substrate enables superior persistence and polyclonal engraftment of genetically engineered hematopoietic stem cells.Cell stem cell · 2026Article
- Molecular and phenotypic blueprint of human hematopoiesis links proliferation stress to stem cell aging.The Journal of experimental medicine · 2026Article
- CRISPR/Cas9 gene editing in hematopoietic stem and progenitor cells to accelerate the translation of cellular therapies and immunotherapies.Journal of translational research · 2026Article
- Gene therapy for hemoglobinopathies: Clinical trial results and biology of hematopoietic stem cell and the bone marrow niche.Cell reports. Medicine · 2025Review
- Leukemic Transdifferentiation: From Pathological Plasticity to Dendritic Cell-Based Immunotherapy.Biomedicines · 2025Review
- A microgel bone marrow model of mesenchymal stem cell paracrine signaling supporting hematopoietic stem cell retention.bioRxiv : the preprint server for biology · 2025Article
- CRISPR-based therapeutic genome editing for inherited blood disorders.Nature reviews. Drug discovery · 2025Review
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Authors and funding
27 authors.
Funding
Abstract
abstractLoss of long-term hematopoietic stem cell (LT-HSC) function ex vivo hampers the success of clinical protocols that rely on culture. However, the kinetics and mechanisms through which this occurs remain incompletely characterized. In this study, through time-resolved single-cell RNA sequencing, matched in vivo functional analysis, and the use of a reversible in vitro system of early G1 arrest, we defined the sequence of transcriptional and functional events that occur during the first ex vivo division of human LT-HSCs. We demonstrated that the sharpest loss in LT-HSC repopulation capacity happens early on, between 6 and 24 hours of culture, before LT-HSCs commit to cell cycle progression. During this time window, LT-HSCs adapt to the culture environment, limit the global variability in gene expression, and transiently upregulate gene networks involved in signaling and stress responses. From 24 hours, LT-HSC progression past early G1 contributes to the establishment of differentiation programs in culture. However, contrary to the current assumptions, we demonstrated that the loss of HSC function ex vivo is independent of cell cycle progression. Finally, we showed that targeting LT-HSC adaptation to culture by inhibiting the early activation of JAK/STAT signaling improves HSC long-term repopulating function ex vivo. Collectively, our study demonstrated that controlling early LT-HSC adaptation to ex vivo culture, for example, via JAK inhibition, is critically important to improve HSC gene therapy and expansion protocols.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.