Home Blog of Signal Transduction Stem Cells & Wnt TGF-beta/Smad Generate hypothalamic neurons from hESCs and human iPSCs

Category

Archives

Popular Post

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer

DASATINIB; An inhibitor of Receptor Tyrosine Kinase

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

Generate hypothalamic neurons from hESCs and human iPSCs

 

Monogenic obesity is reported to be caused by mutations of genes encoding hypothalamic leptin-melanocortin signaling. Due to the inaccessiblility of human hypothalamic, a better understanding of these important pathways requires cultured hypothalamic neurons, which has not been well studied. Wang et al. reported a protocol of differeiciating human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) into hypothalamic cells. The article was published in The Journal of Clinical Investigation.

 

The early activation of sonic hedgehog (SHH) signaling and inhibition of SMAD, followed by Notch signaling inhibition, efficiently converted hESCs into NKX2.1+FOXG1- progenitors, which enable to develop hypothalamic neurons. Researchers further inhibited Notch signaling to develop hypothalamic neurons. The protocol can also be used on human iPSC lines derived from healthy and monogenetic obesity subjects. They measured hypothalamic neuron markers and found signature markers, such as proopimelanocortin (POMC), neuropeptide Y (NPY), agouti-related peptide (AGRP), somatostatin, and dopamine, etc, were expressed in hypothalamic-like neurons. In addition, they didn't express pituitary markers. Moreover, the cells performed characteristics like hypothalamic neurons, such as secretion of neuropeptides and response to insulin and leptin.  The study provides a efficient protocol on generating hypothalamic neuron, leads to a effective strategy of investigation of the neurophysiology.

 

Reference:
J Clin Invest. 2015 Jan 2. pii: 79220. 

Related Products

Cat.No. Product Name Information
S1067 SB431542 SB431542 is a potent and selective inhibitor of ALK5 with IC50 of 94 nM in a cell-free assay, 100-fold more selective for ALK5 than p38 MAPK and other kinases.
S2618 LDN-193189 LDN-193189 (DM3189) is a selective BMP signaling inhibitor, inhibits the ALK1, ALK2, ALK3 and ALK6 with IC50s of 0.8 nM, 0.8 nM, 5.3 nM and 16.7 nM in the kinase assay, respectively. LDN-193189 inhibits the transcriptional activity of the BMP type I receptors ALK2 and ALK3 with IC50s of 5 nM and 30 nM in C2C12 cells, respectively, exhibits 200-fold selectivity for BMP versus TGF-β. For cell testing, the water-soluble S7507 LDN-193189 2HCl is recommended.This product has poor solubility, animal experiments are available, cell experiments please choose carefully!

Related Targets

TGF-beta/Smad