Abstract
Neurons communicate by regulated secretion of chemical signals from synaptic vesicles (SVs) and dense-core vesicles (DCVs). Here, we investigated the maturation of these two secretory pathways in micro-networks of human iPSC-derived neurons. These micro-networks abundantly expressed endogenous SV and DCV markers, including neuropeptides. DCV transport was microtubule dependent, preferentially anterograde in axons, and 2-fold faster in axons than in dendrites. SV and DCV secretion were strictly Ca2+ and SNARE dependent. DCV secretion capacity matured until day in vitro (DIV) 36, with intense stimulation releasing 6% of the total DCV pool, and then plateaued. This efficiency is comparable with mature mouse neurons. In contrast, SV secretion capacity continued to increase until DIV50, with substantial further increase in secretion efficiency and decrease in silent synapses. These data show that the two secretory pathways can be studied in human neurons and that they mature differentially, with DCV secretion reaching maximum efficiency when that of SVs is still low.
| Original language | English |
|---|---|
| Pages (from-to) | 659-672 |
| Number of pages | 14 |
| Journal | Stem Cell Reports |
| Volume | 8 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 14 Mar 2017 |
Cite this
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Differential Maturation of the Two Regulated Secretory Pathways in Human iPSC-Derived Neurons. / Emperador Melero, Javier; Nadadhur, Aishwarya G.; Schut, Desiree; Weering, Jan V.; Heine, Vivi M.; Toonen, Ruud F.; Verhage, Matthijs.
In: Stem Cell Reports, Vol. 8, No. 3, 14.03.2017, p. 659-672.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Differential Maturation of the Two Regulated Secretory Pathways in Human iPSC-Derived Neurons
AU - Emperador Melero, Javier
AU - Nadadhur, Aishwarya G.
AU - Schut, Desiree
AU - Weering, Jan V.
AU - Heine, Vivi M.
AU - Toonen, Ruud F.
AU - Verhage, Matthijs
PY - 2017/3/14
Y1 - 2017/3/14
N2 - Neurons communicate by regulated secretion of chemical signals from synaptic vesicles (SVs) and dense-core vesicles (DCVs). Here, we investigated the maturation of these two secretory pathways in micro-networks of human iPSC-derived neurons. These micro-networks abundantly expressed endogenous SV and DCV markers, including neuropeptides. DCV transport was microtubule dependent, preferentially anterograde in axons, and 2-fold faster in axons than in dendrites. SV and DCV secretion were strictly Ca2+ and SNARE dependent. DCV secretion capacity matured until day in vitro (DIV) 36, with intense stimulation releasing 6% of the total DCV pool, and then plateaued. This efficiency is comparable with mature mouse neurons. In contrast, SV secretion capacity continued to increase until DIV50, with substantial further increase in secretion efficiency and decrease in silent synapses. These data show that the two secretory pathways can be studied in human neurons and that they mature differentially, with DCV secretion reaching maximum efficiency when that of SVs is still low.
AB - Neurons communicate by regulated secretion of chemical signals from synaptic vesicles (SVs) and dense-core vesicles (DCVs). Here, we investigated the maturation of these two secretory pathways in micro-networks of human iPSC-derived neurons. These micro-networks abundantly expressed endogenous SV and DCV markers, including neuropeptides. DCV transport was microtubule dependent, preferentially anterograde in axons, and 2-fold faster in axons than in dendrites. SV and DCV secretion were strictly Ca2+ and SNARE dependent. DCV secretion capacity matured until day in vitro (DIV) 36, with intense stimulation releasing 6% of the total DCV pool, and then plateaued. This efficiency is comparable with mature mouse neurons. In contrast, SV secretion capacity continued to increase until DIV50, with substantial further increase in secretion efficiency and decrease in silent synapses. These data show that the two secretory pathways can be studied in human neurons and that they mature differentially, with DCV secretion reaching maximum efficiency when that of SVs is still low.
KW - dense-core vesicles
KW - human iPSC-derived neurons
KW - neuropeptides
KW - regulated neurosecretion
KW - synaptic transmission
UR - http://www.scopus.com/inward/record.url?scp=85013673299&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2017.01.019
DO - 10.1016/j.stemcr.2017.01.019
M3 - Article
VL - 8
SP - 659
EP - 672
JO - Stem Cell Reports
JF - Stem Cell Reports
SN - 2213-6711
IS - 3
ER -