| Literature DB >> 26607381 |
Felix C Giani1,2,3, Claudia Fiorini1,2, Aoi Wakabayashi1,2, Leif S Ludwig1,2,3,4, Rany M Salem2,5, Chintan D Jobaliya6, Stephanie N Regan2,7, Jacob C Ulirsch1,2, Ge Liang6, Orna Steinberg-Shemer6, Michael H Guo2,5, Tõnu Esko2,5, Wei Tong6, Carlo Brugnara8, Joel N Hirschhorn2,5, Mitchell J Weiss9, Leonard I Zon1,2,7, Stella T Chou6, Deborah L French6, Kiran Musunuru2,7, Vijay G Sankaran1,2.
Abstract
Multipotent and pluripotent stem cells are potential sources for cell and tissue replacement therapies. For example, stem cell-derived red blood cells (RBCs) are a potential alternative to donated blood, but yield and quality remain a challenge. Here, we show that application of insight from human population genetic studies can enhance RBC production from stem cells. The SH2B3 gene encodes a negative regulator of cytokine signaling and naturally occurring loss-of-function variants in this gene increase RBC counts in vivo. Targeted suppression of SH2B3 in primary human hematopoietic stem and progenitor cells enhanced the maturation and overall yield of in-vitro-derived RBCs. Moreover, inactivation of SH2B3 by CRISPR/Cas9 genome editing in human pluripotent stem cells allowed enhanced erythroid cell expansion with preserved differentiation. Our findings therefore highlight the potential for combining human genome variation studies with genome editing approaches to improve cell and tissue production for regenerative medicine.Entities:
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Year: 2015 PMID： 26607381 PMCID： PMC4707983 DOI： 10.1016/j.stem.2015.09.015
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633