Transcriptomics,Genomics

Dataset Information

43

Purification of functional human ES/iPSC-derived midbrain dopaminergic progenitors using LRTM1


ABSTRACT: Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (mDA) neurons for cell replacement therapy for Parkinson's disease (PD). However, iPSC-derived donor cells inevitably contain tumorigenic or inappropriate cells. To eliminate these unwanted cells, cell sorting using antibodies for specific markers such as CORIN or ALCAM have been developed, but neither marker is specific for ventral midbrain. Here, we employed a double-selection strategy for cells expressing both CORIN and LMX1A::GFP and report a novel cell surface marker to enrich mDA progenitors, LRTM1. When transplanted into 6-OHDA-lesioned rats, human iPSC-derived LRTM1+ cells survived and differentiated into mDA neurons in vivo, resulting in significant improvement in motor behavior without tumor formation. In addition, LRTM1+ cells exhibited efficient survival of mDA neurons in the brain of an MPTP-treated monkey. Thus, LRTM1 can provide a powerful tool for efficient and safe cell therapy for PD patients. Overall design: Differentiated mouse ESC-derived neural progenitors just after sorting (day9 CORIN+LMX1A::GFP+, day9 CORIN-LMX1A::GFP+) and mouse fetal ventral mesencephalon on E11.5 (CORIN+, CORIN-) were subjected to RNA extraction and hybridization on Affymetrix microarrays.

INSTRUMENT(S): [MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version]

SUBMITTER: Bumpei Samata  

PROVIDER: GSE72875 | GEO | 2016-09-09

SECONDARY ACCESSION(S): PRJNA295231

REPOSITORIES: GEO

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Publications

Purification of functional human ES and iPSC-derived midbrain dopaminergic progenitors using LRTM1.

Samata Bumpei B   Doi Daisuke D   Nishimura Kaneyasu K   Kikuchi Tetsuhiro T   Watanabe Akira A   Sakamoto Yoshimasa Y   Kakuta Jungo J   Ono Yuichi Y   Takahashi Jun J  

Nature communications 20161014


Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (mDA) neurons for cell replacement therapy for Parkinson's disease (PD). However, iPSC-derived donor cells inevitably contain tumorigenic or inappropriate cells. To eliminate these unwanted cells, cell sorting using antibodies for specific markers such as CORIN or ALCAM has been developed, but neither marker is specific for ventral midbrain. Here we employ a double selection strategy for cells ex  ...[more]

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