Efficient direct reprogramming of mature amniotic cells into endothelial cells by ETS factors and TGFβ suppression.

Abstract:

:ETS transcription factors ETV2, FLI1, and ERG1 specify pluripotent stem cells into induced vascular endothelial cells (iVECs). However, iVECs are unstable and drift toward nonvascular cells. We show that human midgestation c-Kit(-) lineage-committed amniotic cells (ACs) can be reprogrammed into vascular endothelial cells (rAC-VECs) without transitioning through a pluripotent state. Transient ETV2 expression in ACs generates immature rAC-VECs, whereas coexpression with FLI1/ERG1 endows rAC-VECs with a vascular repertoire and morphology matching mature endothelial cells (ECs). Brief TGFβ-inhibition functionalizes VEGFR2 signaling, augmenting specification of ACs into rAC-VECs. Genome-wide transcriptional analyses showed that rAC-VECs are similar to adult ECs in which vascular-specific genes are expressed and nonvascular genes are silenced. Functionally, rAC-VECs form stable vasculature in Matrigel plugs and regenerating livers. Therefore, short-term ETV2 expression and TGFβ inhibition with constitutive ERG1/FLI1 coexpression reprogram mature ACs into durable rAC-VECs with clinical-scale expansion potential. Banking of HLA-typed rAC-VECs establishes a vascular inventory for treatment of diverse disorders.

journal_name

Cell

journal_title

Cell

authors

Ginsberg M,James D,Ding BS,Nolan D,Geng F,Butler JM,Schachterle W,Pulijaal VR,Mathew S,Chasen ST,Xiang J,Rosenwaks Z,Shido K,Elemento O,Rabbany SY,Rafii S

doi

10.1016/j.cell.2012.09.032

subject

Has Abstract

pub_date

2012-10-26 00:00:00

pages

559-75

issue

3

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(12)01178-6

journal_volume

151

pub_type

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