Abstract:
:Generation of hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) could potentially provide unlimited HSCs for clinical transplantation, a curative treatment for numerous blood diseases. However, to date, bona fide HSC generation has been largely unsuccessful in vitro. We have previously described proof of concept for in vivo HSC generation from PSCs via teratoma formation. However, our first-generation system was complex and the output low. Here, we further optimize this technology and demonstrate the following: (1) simplified HSC generation using transcription factor overexpression; (2) improved HSC output using c-Kit-deficient host mice, and (3) that teratomas can be transplanted and cryopreserved. We demonstrate that overexpression of Gfi1b, c-Fos, and Gata2, previously reported to transdifferentiate fibroblasts into hematopoietic progenitors in vitro, can induce long-term HSC formation in vivo. Our in vivo system provides a useful platform to investigate new strategies and re-evaluate existing strategies to generate HSCs and study HSC development.
journal_name
Stem Cell Reportsjournal_title
Stem cell reportsauthors
Tsukada M,Ota Y,Wilkinson AC,Becker HJ,Osato M,Nakauchi H,Yamazaki Sdoi
10.1016/j.stemcr.2017.08.010subject
Has Abstractpub_date
2017-10-10 00:00:00pages
1024-1033issue
4issn
2213-6711pii
S2213-6711(17)30367-3journal_volume
9pub_type
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