Transcriptome and in Vitro Differentiation Profile of Human Embryonic Stem Cell Derived NKX2.1-Positive Neural Progenitors

Chen, Christopher Y.; Plocik, Alex; Anderson, Nickesha C.; Moakley, Daniel F.; Boyi, Trinithas; Dundes, Carolyn E.; Lassiter, Chelsea M.; Graveley, Brenton R.; Grabel, Laura

doi:10.1007/s12015-016-9676-2

Cited by 11 publications

(18 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Quantitative measurements of mRNA expression were performed using the 7300 Real Time PCR System (Applied Biosystems) as previously described [ 12 ].…”

Section: Methodsmentioning

confidence: 99%

“…Characterization of the transcriptomes comparing NKX2.1-positive and NKX2.1-negative populations using shotgun mRNA sequencing (RNA-seq) was performed as previously described [ 12 ]. RNA-Seq data from the BrainSpan Atlas of the Developing Human Brain ( http://brainspan.org ) was assessed as previously described [ 12 ].…”

Section: Methodsmentioning

confidence: 99%

“…This analysis showed that the profile of surfactant associated 3 ( SFTA3 ) expression closely followed NKX2 . 1 , suggesting it was a novel MGE marker that could be involved in interneuron specification [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Examining the role of the surfactant family member SFTA3 in interneuron specification

et al. 2018

Self Cite

View full text Add to dashboard Cite

The transcription factor NKX2.1, expressed at high levels in the medial ganglionic eminence (MGE), is a master regulator of cortical interneuron progenitor development. To identify gene candidates with expression profiles similar to NKX2.1, previous transcriptome analysis of human embryonic stem cell (hESC)-derived MGE-like progenitors revealed SFTA3 as the strongest candidate. Quantitative real-time PCR analysis of hESC-derived NKX2.1-positive progenitors and transcriptome data available from the Allen Institute for Brain Science revealed comparable expression patterns for NKX2.1 and SFTA3 during interneuron differentiation in vitro and demonstrated high SFTA3 expression in the human MGE. Although SFTA3 has been well studied in the lung, the possible role of this surfactant protein in the MGE during embryonic development remains unexamined. To determine if SFTA3 plays a role in MGE specification, SFTA3-/- and NKX2.1 -/- hESC lines were generated using custom designed CRISPRs. We show that NKX2.1 KOs have a significantly diminished capacity to differentiate into MGE interneuron subtypes. SFTA3 KOs also demonstrated a somewhat reduced ability to differentiate down the MGE-like lineage, although not as severe relative to NKX2.1 deficiency. These results suggest NKX2.1 and SFTA3 are co-regulated genes, and that deletion of SFTA3 does not lead to a major change in the specification of MGE derivatives.

show abstract

“…Quantitative measurements of mRNA expression were performed using the 7300 Real Time PCR System (Applied Biosystems) as previously described [ 12 ].…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Examining the role of the surfactant family member SFTA3 in interneuron specification

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…More recent studies have focused on purified, fate-determined populations of hESCs for transplantation. Treating hESCs with the signalling molecule sonic hedgehog (SHH) or a sonic hedgehog agonist (SAG), in combination with modulating the WNT and FGF signalling pathways, can be used in vitro to induce ventral forebrain neural fates and MGE-like cell types [97][98][99][100][103][104][105][106]. Ventralized hESC-derived progenitors have identities similar to that of mouse MGE-derived GABAergic interneuron progenitors, potentially allowing the large-scale in vitro production of human cells for therapies to treat clinical disorders [94].…”

Section: Transplantation Therapy Using Human Embryonic Stem Cell-derimentioning

confidence: 99%

GABAergic Synapse Dysfunction and Repair in Temporal Lobe Epilepsy

Zandt¹,

Naegele²

2017

Synaptic Plasticity

View full text Add to dashboard Cite

Severe medial temporal lobe epilepsy (mTLE) is often associated with pharmacoresistant seizures, impaired memory and mood disorders. In the hippocampus, GABAergic inhibitory interneuron dysfunction and other neural circuit abnormalities contribute to hyperexcitability, but the mechanisms are still not well understood. Experimental approaches aimed at correcting deficits in hippocampal circuits in mTLE include attempts to replace GABAergic interneurons through neural stem cell transplantation. Evidence from studies in rodent mTLE models indicates that transplanted GABAergic progenitor cells integrate into the hippocampus, form inhibitory synapses, reduce seizures and improve cognitive deficits. Here, we review current work in this field and describe potential molecular mechanisms underlying successful transplantation.

show abstract

“…To identify gene candidates with expression profiles similar to NKX2.1 that could also help specify the MGE lineage, we utilized previously published data from our laboratory comparing the RNAseq-based transcriptome of FACS isolated human embryonic stem cell (hESC) -derived NKX2.1-positive progenitors to NKX2.1-negative cells. This analysis showed that the profile of surfactant associated 3 ( SFTA3 ) expression closely followed NKX2.1 , suggesting it was a novel MGE marker that could be involved in interneuron specification (12).…”

Section: Introductionmentioning

confidence: 96%

Examining the Role of the Surfactant Family Member SFTA3 in Interneuron Specification

Chen

Anderson

Becker

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

The transcription factor NKX2.1, expressed at high levels in the medial ganglionic eminence (MGE), is a master regulator of cortical interneuron progenitor development. To identify gene candidates with expression profiles similar to NKX2.1, previous transcriptome analysis of human embryonic stem cell (hESC)-derived MGE-like progenitors revealed SFTA3 as the strongest candidate. Quantitative real-time PCR analysis of hESC-derived NKX2.1-positive progenitors and transcriptome data available from the Allen Institute for Brain Science revealed comparable expression patterns for NKX2.1 and SFTA3 during interneuron differentiation in vitro and demonstrated high SFTA3 expression in the human MGE. Although SFTA3 has been well studied in the lung, the possible role of this surfactant protein in the MGE during embryonic development remains unexamined. To determine if SFTA3 plays a role in MGE specification, SFTA3-/- and NKX2.1 -/-hESC lines were generated using custom designed CRISPRs. We show that NKX2.1 KOs have a significantly diminished capacity to differentiate into MGE interneuron subtypes. SFTA3 KOs also demonstrated a somewhat reduced ability to differentiate down the MGE-like lineage, although not as severe relative to NKX2.1 deficiency. These results suggest NKX2.1 and SFTA3 are co-regulated genes, and that deletion of SFTA3 does not lead to a major change in the specification of MGE derivatives.

show abstract

Transcriptome and in Vitro Differentiation Profile of Human Embryonic Stem Cell Derived NKX2.1-Positive Neural Progenitors

Cited by 11 publications

References 58 publications

Examining the role of the surfactant family member SFTA3 in interneuron specification

Examining the role of the surfactant family member SFTA3 in interneuron specification

GABAergic Synapse Dysfunction and Repair in Temporal Lobe Epilepsy

Examining the Role of the Surfactant Family Member SFTA3 in Interneuron Specification

Contact Info

Product

Resources

About