Related Experiment Video
Updated: Jul 31, 2025
11:00
Reprogramming Mouse Embryonic Fibroblasts with Transcription Factors to Induce a Hemogenic Program
Published on: December 16, 2016
7.3K
Epigenetic programming defines haematopoietic stem cell fate restriction.
Yiran Meng1, Joana Carrelha1,2, Roy Drissen1
1MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Nature Cell Biology
|May 1, 2023
Summary
Haematopoietic stem cells (HSCs) exhibit epigenetic priming for specific cell fates. This epigenetic programming influences both lineage restriction and differentiation speed in HSCs.
Area of Science:
- Hematology
- Epigenetics
- Stem Cell Biology
Background:
- Haematopoietic stem cells (HSCs) are multipotent but can display restricted lineage output.
- The molecular mechanisms and physiological significance of HSC fate restriction are not well understood.
Purpose of the Study:
- To investigate the epigenetic mechanisms underlying HSC fate restriction.
- To determine the role of epigenetic programming in predicting HSC lineage output and differentiation kinetics.
Main Methods:
- Comparative analysis of chromatin accessibility in multi-lineage versus platelet-biased HSCs.
- Assessment of gene expression, specifically Runx3.
- Evaluation of progenitor cell output and differentiation kinetics.
Main Results:
- Lymphoid fate is epigenetically primed in HSCs via accessible lymphoid-specific upstream regulatory elements (LymUREs), without transcriptional activation.
- Runx3 expression promotes LymURE accessibility and lymphoid-primed multipotent progenitor 4 (MPP4) output.
- Platelet-biased HSCs exhibit epigenetic priming for platelet lineage, leading to faster platelet production kinetics via MPP2 progenitors.
Conclusions:
- Epigenetic programming, rather than transcriptional status alone, dictates HSC fate restriction.
- Epigenetic modifications in HSCs predict not only lineage commitment but also the kinetics of progenitor differentiation and cell output.
More Related Videos
Related Concept Videos
01:21Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K
01:01Regulation of Hematopoietic Stem Cells
3.3K
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.3K
01:24Methods of Nuclear Reprogramming
1.9K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
1.9K
01:14Maintenance of the ES Cell State
2.2K
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
2.2K
01:19Multipotency of Hematopoietic Stem Cells
3.2K
The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
3.2K
01:32Chromatin Modification in iPS Cells
1.7K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.7K