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Engineering Hematopoietic Stem Cells: Lessons from Development.


ABSTRACT: Cell engineering has brought us tantalizingly close to the goal of deriving patient-specific hematopoietic stem cells (HSCs). While directed differentiation and transcription factor-mediated conversion strategies have generated progenitor cells with multilineage potential, to date, therapy-grade engineered HSCs remain elusive due to insufficient long-term self-renewal and inadequate differentiated progeny functionality. A cross-species approach involving zebrafish and mammalian systems offers complementary methodologies to improve understanding of native HSCs. Here, we discuss the role of conserved developmental timing processes in vertebrate hematopoiesis, highlighting how identification and manipulation of stage-specific factors that specify HSC developmental state must be harnessed to engineer HSCs for therapy.

SUBMITTER: Rowe RG 

PROVIDER: S-EPMC4911194 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Engineering Hematopoietic Stem Cells: Lessons from Development.

Rowe R Grant RG   Mandelbaum Joseph J   Zon Leonard I LI   Daley George Q GQ  

Cell stem cell 20160601 6


Cell engineering has brought us tantalizingly close to the goal of deriving patient-specific hematopoietic stem cells (HSCs). While directed differentiation and transcription factor-mediated conversion strategies have generated progenitor cells with multilineage potential, to date, therapy-grade engineered HSCs remain elusive due to insufficient long-term self-renewal and inadequate differentiated progeny functionality. A cross-species approach involving zebrafish and mammalian systems offers co  ...[more]

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