iPSC疾病建模篇–培养皿里的疼痛

Nav1.7PaininaDish

iPSC

Neil Andrews1 Apr 2019

DRG(iPSCs)(iPSCSNs)PaininaDishNav1.7

 

Stephen WaxmanNav1.7(IEM)nav1.7s241tiPSCSNsKCNQ2

 

Ted Price15

 

2019116Journal of Neuroscience

 

David Bennett使iPSCSNsNav1.7(CIP)WaxmaniPSCSNs

 

Angelika Lampert:Nav1.7iPSCNav1.7 LampertiPSCSNsNav1.7Bennett201936(Neuron)WaxmanSulayman DibHajjPreview

 

 

WaxmanIEMIEM2009WaxmanIEMV400MNav1.7西(Fischer et al.2009)

 

William CatterallPayandeh et al ., 2011, WaxmanNav1.7V400M西S241T(Yang et al.2012)

 

Nav1.7S241TV400MYang Yang et al., Nature Communications volume3,Article number: 1186 (2012)

IEMS241T西(Geha et al. 2016)14

 

S241T ? ?

 

iPSCSNsIEMS241T

 

iPSCsWaxman

 

 

iPSCSNsS241TiPSCSNs(MEAAxion Mastro Pro)iPSCSNs(MEA)pattern

MEAP300[]P301[]P303[]iPSCSNsAPMEA: /; /8X8iPSCSNs33°C37°C40°CiPSCSNs33°C37°C40°CiPSCSNs33°C37°C40°CMis et al. J Neurosci. 2019 Jan 16; 39(3):38292

iPSC(Purdue University):

 

Axion Mastro MEA

Malgorzata MisiPSCSN; ; iPSCSNs

 

iPSCs

 

44Mis

 

 

iPSCSN使 ingenuity pathway analysis (IPA)(DRG)

 

90KCNQ2KCNQ2Kv7.2DRGM

 

PricePRF:

 

使()

 

Waxman

 

 

WaxmanKCNQ2

 

?

 

Waxman

 

iPSCSNiPSCs Waxman

 

iPSCSNsPriceDRGDRG

 

 

BennettiPSCSNsNav1.7CIPBennettNav1.7

 

Nav1.7:???Bennett

 

?

 

iPSCSNsCIPsensory profilingNav1.7compound heterozygous mutations(QST)MDTVDT

 

()C

 

CIP BennettCIPCIPNav1.7

 

(D)(E)CIP线线50μmMcDermott et al. Neuron. 2019 Mar 6;101(5):905919.e8

 

Nav1.7 KO30? UCLJohn WoodPRF

 

CIPNav1.7

 

 

使arterial spin labelingCIP

 

NPS, Wager et al., 2013CIPNPS

 

CIP Bennett

 

sensory modalities,,,, Bennett

 

flare reaction

 

C(CMiC) Bennett

 

? Nav1.7Lampert?

 

Paininadish

 

iPSCSNsCIPiPSCSNsNav1.7DRGCRISPR(HA)Nav1.7trafficking

 

Lucy McDermottGreg Weir:Nav1.7HAiPSCCRISPRMcDermott :Nav1.7 齿DRGNav1.7iPSCSNsSchwannNav1.7

 

Nav1.7CIPiPSCSNsCIP

 

CRISPRCIPiPSCSNsSCN9A(Nav1.7)CIPiPSCSNsNav1.7iPSCSNs

 

? CIP Weir

 

Lampert:iPSCSNNav1.7CIPIEMiPSCSNsIEF(Meents et al.2019)

 

iPSCSNs

 

Wood(Minett et al. 2015)iPSCSNNav1.7Nav1.7 KO iPSCSNs使naloxoneNav1.7

 

iPSCSNNav1.7

 

WeirNav1.7 Nav1.7Nav1.7

 

iPSCSNsNav1.7Weir:

 

iPSCSNLampertiPSCSNs (Nameret al. 2019)LacosamideiPSCSNs10iPSCSNs

 

iPSCSNs

 

Bennett

 

iPSCSNs

 

Bennett