Examining the Role of the Surfactant Family Member SFTA3 in Interneuron Specification
Autor: | Friedrich Paulsen, Sandy Becker, Lars Bräuer, Laura Grabel, Nickesha C. Anderson, Christopher Y. Chen, Martin Schicht, Christopher E Stoddard |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Surfactants Cellular differentiation lcsh:Medicine Gene Expression Biochemistry Transcriptome Animal Cells Medizinische Fakultät Gene expression Clustered Regularly Interspaced Short Palindromic Repeats lcsh:Science Materials Neurons Multidisciplinary Brain Cell Differentiation Genomics Cell biology medicine.anatomical_structure Physical Sciences embryonic structures Cytochemistry Cellular Types Transcriptome Analysis Immunocytochemistry Neuronal Differentiation Research Article Pulmonary Surfactant-Associated Proteins Ganglionic eminence Interneuron Neurogenesis Materials Science Biology Cell Line 03 medical and health sciences Interneurons Genetics medicine Humans Cell Lineage ddc:610 Progenitor cell Gene Transcription factor Embryonic Stem Cells Progenitor lcsh:R Biology and Life Sciences Computational Biology Cell Biology Genome Analysis Embryonic stem cell 030104 developmental biology Cellular Neuroscience lcsh:Q Neuroscience Developmental Biology |
Zdroj: | PLoS ONE PLoS ONE, Vol 13, Iss 11, p e0198703 (2018) |
DOI: | 10.1101/330621 |
Popis: | The transcription factorNKX2.1, 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 toNKX2.1, previous transcriptome analysis of human embryonic stem cell (hESC)-derived MGE-like progenitors revealedSFTA3as 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 forNKX2.1andSFTA3during interneuron differentiationin vitroand demonstrated highSFTA3expression in the human MGE. AlthoughSFTA3has been well studied in the lung, the possible role of this surfactant protein in the MGE during embryonic development remains unexamined. To determine ifSFTA3plays a role in MGE specification,SFTA3-/- andNKX2.1 -/-hESC lines were generated using custom designed CRISPRs. We show thatNKX2.1KOs have a significantly diminished capacity to differentiate into MGE interneuron subtypes.SFTA3KOs also demonstrated a somewhat reduced ability to differentiate down the MGE-like lineage, although not as severe relative toNKX2.1deficiency. These results suggestNKX2.1andSFTA3are co-regulated genes, and that deletion ofSFTA3does not lead to a major change in the specification of MGE derivatives. |
Databáze: | OpenAIRE |
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