Induction of Multipotential Hematopoietic Progenitors from Human Pluripotent Stem Cells via Respecification of Lineage-Restricted Precursors

被引：240

作者：

Doulatov, Sergei ^{[1
,2
,3
,4
]}

Vo, Linda T. ^{[1
,2
,3
,4
]}

Chou, Stephanie S. ^{[1
,2
,3
,4
]}

Kim, Peter G. ^{[1
,2
,3
,4
]}

Arora, Natasha ^{[1
,2
,3
,4
]}

Li, Hu ^{[5
,6
,7
]}

Hadland, Brandon K. ^{[8
,9
]}

Bernstein, Irwin D. ^{[8
,9
]}

Collins, James J. ^{[5
,6
,7
]}

Zon, Leonard I. ^{[4
,10
,11
]}

Daley, George Q. ^{[1
,2
,3
,4
,11
]}

机构：

[1] Childrens Hosp, Howard Hughes Med Inst, Stem Cell Transplantat Program, Div Pediat Hematol Oncol,Manton Ctr Orphan Dis Re, Boston, MA 02115 USA

[2] Dana Farber Canc Inst, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[4] Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[5] Boston Univ, Howard Hughes Med Inst, Dept Biomed Engn, Boston, MA 02215 USA

[6] Boston Univ, Ctr BioDynam, Boston, MA 02215 USA

[7] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA

[8] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA

[9] Univ Washington, Dept Pediat, Seattle, WA 98105 USA

[10] Childrens Hosp, Howard Hughes Med Inst, Div Pediat Hematol Oncol, Stem Cell Program, Boston, MA 02115 USA

[11] Broad Inst, Cambridge, MA 02141 USA

来源：

CELL STEM CELL | 2013年 / 13卷 / 04期

关键词：

RED-BLOOD-CELLS; REPOPULATING ABILITY; IN-VITRO; DIFFERENTIATION; GENERATION; EXPRESSION; MACROPHAGES; PATIENT;

D O I：

10.1016/j.stem.2013.09.002

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

Human pluripotent stem cells (hPSCs) represent a promising source of patient-specific cells for disease modeling, drug screens, and cellular therapies. However, the inability to derive engraftable human hematopoietic stem and progenitor cells (HSPCs) has limited their characterization to in vitro assays. We report a strategy to respecify lineage-restricted CD34(+)CD45(+) myeloid precursors derived from hPSCs into multilineage progenitors that can be expanded in vitro and engrafted in vivo. HOXA9, ERG, and RORA conferred self-renewal and multilineage potential in vitro and maintained primitive CD34(+)CD38(-) cells. Screening cells via transplantation revealed that two additional factors, SOX4 and MYB, conferred engraftment. Progenitors specified with all five factors gave rise to reproducible short-term engraftment with myeloid and erythroid lineages. Erythroid precursors underwent hemoglobin switching in vivo, silencing embryonic and activating adult globin expression. Our combinatorial screening approach establishes a strategy for obtaining transcription-factor-mediated engraftment of blood progenitors from human pluripotent cells.

引用

页码：459 / 470

页数：12

共 47 条

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Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients [J].