In Vivo Generation of Engraftable Murine Hematopoietic Stem Cells by Gfi1b, c-Fos, and Gata2 Overexpression within Teratoma.

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 Reports

journal_title

Stem cell reports

authors

Tsukada M,Ota Y,Wilkinson AC,Becker HJ,Osato M,Nakauchi H,Yamazaki S

doi

10.1016/j.stemcr.2017.08.010

subject

Has Abstract

pub_date

2017-10-10 00:00:00

pages

1024-1033

issue

4

issn

2213-6711

pii

S2213-6711(17)30367-3

journal_volume

9

pub_type

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