Single-cell multiomics of pediatric BM reveals age-dependent differences in lineage differentiation linked to stromal cell heterogeneity
Hanemaaijer, E. S.; Muskens, K. F.; Kal, I. J.; te Pas, B. M.; Fryzik, P.; Epskamp, N.; Balwierz, A.; Candelli, T.; de Jonge, W. J.; Margaritis, T.; Belderbos, M. E.
Show abstract
Childhood is critical for hematopoietic development and the onset of hematologic diseases. To explore hematopoietic changes from infancy through adolescence, we generated a multi-modal single-cell atlas capturing mRNA and surface protein expression of 90.710 bone marrow (BM) cells. This includes hematopoietic stem/progenitor cells and mesenchymal stromal cells, from seven pediatric individuals and two young adults. We demonstrate that young pediatric BM is distinct from adolescents/young adults (AYA), shifting from B-lineage dominance in early childhood to myeloid and T-lineage bias in adolescence. We uncover two distinct lymphoid progenitors (LyPs) subsets regulating this shift: CD127-positive LyPs with B-lineage output, most abundant in early childhood, and CD127-negative LyPs with lymphoid and myeloid features, more common in AYAs. Age-related changes in stromal composition and signaling, mediated by IL-7 and TGF-{beta}1, correspond with this lineage shift. This study provides an in-depth resource for understanding healthy hematologic development and potential early-life perturbations underlying pediatric hematologic diseases.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Lfc/Arhgef2 regulates mitotic spindle orientation in hematopoietic stem and progenitor cells and is essential for productive hematopoiesis 96%
- Basal type I interferon signaling has only modest effects on neonatal and juvenile hematopoiesis 96%
- Redundant mechanisms driven independently by RUNX1 and GATA2 for hematopoietic development 96%
Similar papers in this journal
Similar papers in this journal
- Expression of terminal deoxynucleotidyl transferase (TdT) identifies lymphoid-primed progenitors in human bone marrow 97%
- Engineered niches support the development of human dendritic cells in humanized mice 97%
- Multi-Modal Profiling of Human Fetal Liver-Derived Hematopoietic Stem Cells Reveals the Molecular Signature of Engraftment Potential 96%
Similar papers in this journal
- A single cell framework identifies functionally and molecularly distinct multipotent progenitors in adult human hematopoiesis 98%
- Global transcriptomic profiling of the bone marrow stromal microenvironment during postnatal development, aging and inflammation 96%
- Concurrent stem- and lineage-affiliated chromatin programs precede hematopoietic lineage restriction 95%
Similar papers in this journal
- Tropomyosin 1 deficiency facilitates cell state transitions and enhances hemogenic endothelial cell specification during hematopoiesis 96%
- Developmental regulation of endothelial-to-hematopoietic transition from induced pluripotent stem cells 96%
- Developmental stage-specific changes in protein synthesis differentially sensitize hematopoietic stem cells and erythroid progenitors to impaired ribosome biogenesis 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.