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Reprogramming Mouse Embryonic Fibroblasts with Transcription Factors to Induce a Hemogenic Program
Published on: December 16, 2016
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Reprogramming mouse fibroblasts into engraftable myeloerythroid and lymphoid progenitors
Hui Cheng1, Heather Yin-Kuan Ang1, Chadi A El Farran2,3
1Stem Cell and Regenerative Biology Group, Genome Institute of Singapore, Singapore 138672, Singapore.
Nature Communications
|November 22, 2016
Summary
Scientists converted fibroblasts into induced hematopoietic progenitors (iHPs) using key transcription factors. These iHPs generate various blood cells and engraft in mice, offering a new route for blood cell generation.
Area of Science:
- Stem cell biology
- Hematopoiesis
- Cellular reprogramming
Background:
- Generating hematopoietic stem cells (HSCs) from non-blood cells is a key goal for regenerative medicine.
- Previous efforts focused on direct conversion to HSCs, with limited success.
Purpose of the Study:
- To investigate if specific hematopoietic transcription factors can reprogram fibroblasts into functional blood progenitors.
- To characterize the properties and potential of these reprogrammed cells.
Main Methods:
- Fibroblasts were reprogrammed using a cocktail of hematopoietic transcription factors (Scl, Lmo2, Runx1, Bmi1).
- Induced hematopoietic progenitors (iHPs) were analyzed for in vitro differentiation potential.
- iHPs were engrafted into immunodeficient mice to assess in vivo hematopoiesis.
Main Results:
- Reprogramming yielded induced hematopoietic progenitors (iHPs) that resemble native hematopoietic progenitors.
- iHPs differentiated into megakaryocytes and myeloid cells in vitro.
- Engrafted iHPs generated myeloerythroid and B-lymphoid cells in vivo for up to 4 months.
- Lmo2 was identified as a key factor, upregulating Hhex and Gfi1 to initiate the hematopoietic program.
- Extracellular BMP and MEK signaling were found to be essential for efficient reprogramming.
Conclusions:
- Hematopoietic transcription factors can artificially reconstitute the embryonic hematopoiesis program in fibroblasts.
- This process generates engraftable induced hematopoietic progenitors from a developmentally distant lineage.
- This study provides a novel strategy for de novo blood cell generation.
