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Related Concept Videos

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The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
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Engineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics.

Brandon Hadland1,2, Barbara Varnum-Finney3, Stacey Dozono3

  • 1Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. bhadland@fredhutch.org.

Nature Communications
|March 25, 2022
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Summary
This summary is machine-generated.

Researchers identified key signals that guide the development of hematopoietic stem cells (HSCs) from hemogenic endothelium. These signals, including Notch, VLA-4, and CXCR4, are crucial for HSC maturation and self-renewal, paving the way for engineered HSC therapies.

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A Combinatorial Single-cell Approach to Characterize the Molecular and Immunophenotypic Heterogeneity of Human Stem and Progenitor Populations
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Area of Science:

  • Developmental biology
  • Stem cell biology
  • Molecular signaling

Background:

  • Hematopoietic stem cells (HSCs) originate from hemogenic endothelium in embryonic arterial vessels.
  • The aorta-gonad-mesonephros (AGM) region is a critical site for early HSC development.

Purpose of the Study:

  • To identify the specific molecular signals involved in the transition from hemogenic endothelium to HSCs.
  • To understand the transcriptional dynamics during HSC development.
  • To explore the potential for engineering HSCs for therapeutic use.

Main Methods:

  • Single-cell RNA sequencing was employed to analyze transcriptional profiles of AGM-derived cells.
  • Pseudotemporal ordering was used to map gene expression dynamics during HSC development.
  • Transcriptional profiling of niche endothelial cells identified key signaling ligands.

Main Results:

  • Identified surface receptors on developing HSCs and corresponding ligands on niche endothelial cells.
  • Discovered signaling interactions involving Notch receptors, VLA-4 integrin, and CXCR4.
  • Demonstrated that these integrated signals can support the generation of engrafting HSCs in an engineered platform.

Conclusions:

  • Provided a comprehensive transcriptional map of signaling interactions essential for HSC development.
  • Established that specific signaling pathways are sufficient to promote HSC maturation and self-renewal.
  • Advanced the field's ability to engineer HSCs for potential therapeutic applications.