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Updated: Sep 23, 2025
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Clonal Analysis of Embryonic Hematopoietic Stem Cell Precursors Using Single Cell Index Sorting Combined with Endothelial Cell Niche Co-culture
Published on: May 8, 2018
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Concurrent stem- and lineage-affiliated chromatin programs precede hematopoietic lineage restriction
Fatemeh Safi1, Parashar Dhapola1, Sarah Warsi1
1Division of Molecular Hematology, Lund Stem Cell Center, Lund University, BMC B12, 22184 Lund, Sweden.
Cell Reports
|May 11, 2022
Summary
Hematopoietic stem cells (HSPCs) are not fully differentiated. A specific cell population shows early lineage priming, bridging stemness and commitment, revealing critical transitions in blood cell development.
Area of Science:
- Hematology
- Stem Cell Biology
- Epigenetics
Background:
- Hematopoietic stem and progenitor cells (HSPCs) are considered a low-primed state.
- Understanding lineage commitment initiation in HSPCs is crucial for deciphering blood development.
Purpose of the Study:
- To investigate the chromatin accessibility landscape of HSPCs during early differentiation.
- To identify the stage at which lineage priming begins in hematopoietic stem cells.
Main Methods:
- Single-cell chromatin accessibility profiling of Lineage-, cKit+, Sca1+ (LSK) HSPCs.
- Utilized a signal-processing algorithm to analyze transcription factor motif accessibility.
- Characterized a specific LSK FMS-like tyrosine kinase 3 (Flt3)intCD9high cell population.
Main Results:
- Identified a distinct LSK Flt3intCD9high cell population.
- These cells exhibit both stem-like and lineage-affiliated chromatin signatures.
- Demonstrated simultaneous gain of lympho-myeloid and megakaryocyte-erythroid programs in these cells.
Conclusions:
- LSK Flt3intCD9high cells represent an intermediate stage between stem cells and committed progenitors.
- These cells possess multi-lineage potential but lack self-renewal capacity.
- This study elucidates chromatin-mediated transitions from multipotency to lineage restriction in hematopoiesis.
Keywords:
CD9CP: Cell biologyCP: Developmental biologyFlt3hematopoietic stem cellslineage commitmentsingle-cell ATAC sequencingsingle-cell RNA sequencingtransition stateMore Related Videos
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