Selective conversion of fibroblasts into peripheral sensory neurons.
Selective conversion of fibroblasts into peripheral sensory neurons.
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DOI：
10.1038/nn.3887
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发表时间：
2015-01
影响因子：
25
通讯作者：
Baldwin, Kristin K.
中科院分区：
文献类型：
--
作者：
Blanchard, Joel W.;Eade, Kevin T.;Szucs, Attila;Lo Sardo, Valentina;Tsunemoto, Rachel K.;Williams, Daniel;Sanna, Pietro Paolo;Baldwin, Kristin K.
人类和小鼠通过外周感觉神经元的信号来检测疼痛、瘙痒、温度、压力、拉伸和肢体位置。这些神经元分为三个功能类别（伤害感受器/刺激感受器、机械感受器和本体感受器），其分别通过其选择性表达TrkA、TrkB或TrkC受体来区分。我们发现，瞬时共表达Brn3a与Ngn 1或Ngn 2选择性地重编程人类和小鼠成纤维细胞，以获得这三类感觉神经元的关键特性。这些诱导的感觉神经元（iSN）是电活性的，表现出不同的感觉神经元形态，并匹配内源性感觉神经元的特征性基因表达模式，包括选择性表达Trk受体。此外，我们发现钙成像检测可以识别iSN的子集，这些iSN选择性地响应于已知激活瘙痒和疼痛感应神经元的各种配体。这些结果提供了一个简单而快速的方法来产生适合药物筛选和机制研究的遗传多样性的人类感觉神经元。
Humans and mice detect pain, itch, temperature, pressure, stretch and limb position via signaling from peripheral sensory neurons. These neurons are divided into three functional classes (nociceptors/pruritoceptors, mechanoreceptors and proprioceptors) that are distinguished by their selective expression of TrkA, TrkB or TrkC receptors, respectively. We found that transiently coexpressing Brn3a with either Ngn1 or Ngn2 selectively reprogrammed human and mouse fibroblasts to acquire key properties of these three classes of sensory neurons. These induced sensory neurons (iSNs) were electrically active, exhibited distinct sensory neuron morphologies and matched the characteristic gene expression patterns of endogenous sensory neurons, including selective expression of Trk receptors. In addition, we found that calcium-imaging assays could identify subsets of iSNs that selectively responded to diverse ligands known to activate itch- and pain-sensing neurons. These results offer a simple and rapid means for producing genetically diverse human sensory neurons suitable for drug screening and mechanistic studies.
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影响因子：
2.5
作者：
Lanier, Jason;Dykes, Iain M.;Nissen, Stephanie;Eng, S. Raisa;Turner, Eric E.
通讯作者：
Turner, Eric E.
影响因子：
64.5
作者：
Li L;Rutlin M;Abraira VE;Cassidy C;Kus L;Gong S;Jankowski MP;Luo W;Heintz N;Koerber HR;Woodbury CJ;Ginty DD
通讯作者：
Ginty DD
影响因子：
56.9
作者：
Lanier, L. H.
通讯作者：
Lanier, L. H.
影响因子：
12.7
作者：
Koeppen, Arnulf H.;Morral, Jennifer A.;Li, Danhong
通讯作者：
Li, Danhong
影响因子：
3.7
作者：
Addis RC;Hsu FC;Wright RL;Dichter MA;Coulter DA;Gearhart JD
通讯作者：
Gearhart JD