Transcriptome analysis reveals transmembrane targets on transplantable midbrain dopamine progenitors.
Bye, Chris R ; Jönsson, Marie LU ; Björklund, Anders LU
; Parish, Clare L
and Thompson, Lachlan
LU
(2015)
In Proceedings of the National Academy of Sciences
112(15).
p.1946-1955
- Abstract
- An important challenge for the continued development of cell therapy for Parkinson's disease (PD) is the establishment of procedures that better standardize cell preparations for use in transplantation. Although cell sorting has been an anticipated strategy, its application has been limited by lack of knowledge regarding transmembrane proteins that can be used to target and isolate progenitors for midbrain dopamine (mDA) neurons. We used a "FACS-array" approach to identify 18 genes for transmembrane proteins with high expression in mDA progenitors and describe the utility of four of these targets (Alcam, Chl1, Gfra1, and Igsf8) for isolating mDA progenitors from rat primary ventral mesencephalon through flow cytometry. Alcam and Chl1... (More)
- An important challenge for the continued development of cell therapy for Parkinson's disease (PD) is the establishment of procedures that better standardize cell preparations for use in transplantation. Although cell sorting has been an anticipated strategy, its application has been limited by lack of knowledge regarding transmembrane proteins that can be used to target and isolate progenitors for midbrain dopamine (mDA) neurons. We used a "FACS-array" approach to identify 18 genes for transmembrane proteins with high expression in mDA progenitors and describe the utility of four of these targets (Alcam, Chl1, Gfra1, and Igsf8) for isolating mDA progenitors from rat primary ventral mesencephalon through flow cytometry. Alcam and Chl1 facilitated a significant enrichment of mDA neurons following transplantation, while targeting of Gfra1 allowed for robust separation of dopamine and serotonin neurons. Importantly, we also show that mDA progenitors isolated on the basis of transmembrane proteins are capable of extensive, functional innervation of the host striatum and correction of motor impairment in a unilateral model of PD. These results are highly relevant for current efforts to establish safe and effective stem cell-based procedures for PD, where clinical translation will almost certainly require safety and standardization measures in order to deliver well-characterized cell preparations. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/5258542
- author
- Bye, Chris R
; Jönsson, Marie
LU
; Björklund, Anders
LU
; Parish, Clare L
and Thompson, Lachlan
LU
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Proceedings of the National Academy of Sciences
- volume
- 112
- issue
- 15
- pages
- 1946 - 1955
- publisher
- National Academy of Sciences
- external identifiers
-
- pmid:25775569
- wos:000352856800019
- scopus:84928038755
- pmid:25775569
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.1501989112
- language
- English
- LU publication?
- yes
- id
- 94d31b64-d342-498f-88c8-c595a926c004 (old id 5258542)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/25775569?dopt=Abstract
- date added to LUP
- 2016-04-01 10:21:50
- date last changed
- 2022-04-04 17:23:16
@article{94d31b64-d342-498f-88c8-c595a926c004,
abstract = {{An important challenge for the continued development of cell therapy for Parkinson's disease (PD) is the establishment of procedures that better standardize cell preparations for use in transplantation. Although cell sorting has been an anticipated strategy, its application has been limited by lack of knowledge regarding transmembrane proteins that can be used to target and isolate progenitors for midbrain dopamine (mDA) neurons. We used a "FACS-array" approach to identify 18 genes for transmembrane proteins with high expression in mDA progenitors and describe the utility of four of these targets (Alcam, Chl1, Gfra1, and Igsf8) for isolating mDA progenitors from rat primary ventral mesencephalon through flow cytometry. Alcam and Chl1 facilitated a significant enrichment of mDA neurons following transplantation, while targeting of Gfra1 allowed for robust separation of dopamine and serotonin neurons. Importantly, we also show that mDA progenitors isolated on the basis of transmembrane proteins are capable of extensive, functional innervation of the host striatum and correction of motor impairment in a unilateral model of PD. These results are highly relevant for current efforts to establish safe and effective stem cell-based procedures for PD, where clinical translation will almost certainly require safety and standardization measures in order to deliver well-characterized cell preparations.}},
author = {{Bye, Chris R and Jönsson, Marie and Björklund, Anders and Parish, Clare L and Thompson, Lachlan}},
issn = {{1091-6490}},
language = {{eng}},
number = {{15}},
pages = {{1946--1955}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences}},
title = {{Transcriptome analysis reveals transmembrane targets on transplantable midbrain dopamine progenitors.}},
url = {{http://dx.doi.org/10.1073/pnas.1501989112}},
doi = {{10.1073/pnas.1501989112}},
volume = {{112}},
year = {{2015}},
}