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Hemogenic Endothelium Differentiation from Human Pluripotent Stem Cells in A Feeder- and Xeno-free Defined Condition
Published on: June 16, 2019
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Haematopoietic stem and progenitor cells from human pluripotent stem cells
Ryohichi Sugimura1,2,3,4, Deepak Kumar Jha1,2,3,4, Areum Han1,2
1Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Nature
|May 18, 2017
Summary
Researchers generated functional human hematopoietic stem cells from pluripotent stem cells. Seven transcription factors were identified to convert hemogenic endothelium into stem and progenitor cells, enabling multi-lineage blood cell engraftment.
Area of Science:
- Stem cell biology
- Hematopoiesis
- Gene regulation
Background:
- Pluripotent stem cells can differentiate into various tissues by mimicking embryonic development.
- Cell fate can be altered by expressing specific master transcription factors.
Purpose of the Study:
- To generate functional human hematopoietic stem cells (HSCs) from pluripotent stem cells.
- To identify key transcription factors that promote HSC development and multi-lineage engraftment.
Main Methods:
- Morphogen-directed differentiation of human pluripotent stem cells into hemogenic endothelium.
- Screening of 26 candidate transcription factors for HSC-specifying capacity.
- Assessment of multi-lineage hematopoietic engraftment in mouse models.
Main Results:
- Seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1, SPI1) were identified.
- These factors converted hemogenic endothelium into HSCs and progenitor cells.
- Generated cells engrafted myeloid, B, and T cells in primary and secondary mouse recipients.
Conclusions:
- A combined approach of morphogen differentiation and transcription factor conversion yields functional HSCs from pluripotent stem cells.
- This method shows promise for modeling hematologic diseases in humanized mice.
- Potential therapeutic applications for genetic blood disorders.
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