ArticleGenome biology2015
Single-cell transcriptomic reconstruction reveals cell cycle and multi-lineage differentiation defects in Bcl11a-deficient hematopoietic stem cells.
Article in Genome biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed.
- Post-Transcriptional Genetic Silencing ofThe New England journal of medicine · 2021Trial
- Integrating Single-Cell Sequencing and Proteomics to Unravel Stem Cell Heterogeneity: Implications for Precision Regenerative Medicine.Stem cell reviews and reports · 2026Review
- Leukemia mutated proteins PHF6 and PHIP form a chromatin complex that represses acute myeloid leukemia stemness.Genes & development · 2025Article
- The transcription factor Bcl11a is essential for B-1a cell maintenance during aging.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Upregulation of miR‑6747‑3p affects red blood cell lineage development and induces fetal hemoglobin expression by targeting BCL11A in β‑thalassemia.Molecular medicine reports · 2025Article
- The glucocorticoid receptor elicited proliferative response in human erythropoiesis is BCL11A-dependent.Stem cells (Dayton, Ohio) · 2024Article
- Base editing of key residues in the BCL11A-XL-specific zinc finger domains derepresses fetal globin expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Single-cell transcriptomic analysis reveals heterogeneous features of myeloid-derived suppressor cells in newborns.Frontiers in immunology · 2024Article
- Single-cell proteomics enabled by next-generation sequencing or mass spectrometry.Nature methods · 2023Review
- Multi-lineage Differentiation from Hematopoietic Stem Cells.Advances in experimental medicine and biology · 2023Review
- ID2 and HIF-1α collaborate to protect quiescent hematopoietic stem cells from activation, differentiation, and exhaustion.The Journal of clinical investigation · 2022Article
- Gene Editing-Based Technologies forBiology · 2022Review
- Down-regulation of the transcriptional repressor ZNF802 (JAZF1) reactivates fetal hemoglobin in βScientific reports · 2022Article
- Single-Cell Sequencing Technologies in Precision Oncology.Advances in experimental medicine and biology · 2022Review
- Implications of hematopoietic stem cells heterogeneity for gene therapies.Gene therapy · 2021Review
- ZNF410 represses fetal globin by singular control of CHD4.Nature genetics · 2021Article
- Single-cell RNA-seq reveals a concomitant delay in differentiation and cell cycle of aged hematopoietic stem cells.BMC biology · 2021Article
- Therapeutic Targeting of Cancer: Epigenetic Homeostasis.Frontiers in oncology · 2021Review
- Physiological and Aberrant γ-Globin Transcription During Development.Frontiers in cell and developmental biology · 2021Review
6 more citing papers are in PubMed but not listed here.
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9 authors.
Funding
Abstract
backgroundHematopoietic stem cells (HSCs) are a rare cell type with the ability of long-term self-renewal and multipotency to reconstitute all blood lineages. HSCs are typically purified from the bone marrow using cell surface markers. Recent studies have identified significant cellular heterogeneities in the HSC compartment with subsets of HSCs displaying lineage bias. We previously discovered that the transcription factor Bcl11a has critical functions in the lymphoid development of the HSC compartment.
resultsIn this report, we employ single-cell transcriptomic analysis to dissect the molecular heterogeneities in HSCs. We profile the transcriptomes of 180 highly purified HSCs (Bcl11a (+/+) and Bcl11a (-/-)). Detailed analysis of the RNA-seq data identifies cell cycle activity as the major source of transcriptomic variation in the HSC compartment, which allows reconstruction of HSC cell cycle progression in silico. Single-cell RNA-seq profiling of Bcl11a (-/-) HSCs reveals abnormal proliferative phenotypes. Analysis of lineage gene expression suggests that the Bcl11a (-/-) HSCs are constituted of two distinct myeloerythroid-restricted subpopulations. Remarkably, similar myeloid-restricted cells could also be detected in the wild-type HSC compartment, suggesting selective elimination of lymphoid-competent HSCs after Bcl11a deletion. These defects are experimentally validated in serial transplantation experiments where Bcl11a (-/-) HSCs are myeloerythroid-restricted and defective in self-renewal.
conclusionsOur study demonstrates the power of single-cell transcriptomics in dissecting cellular process and lineage heterogeneities in stem cell compartments, and further reveals the molecular and cellular defects in the Bcl11a-deficient HSC compartment.
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