2022
DOI: 10.1038/s41467-022-29942-w
|View full text |Cite
|
Sign up to set email alerts
|

Transcription Factor 4 loss-of-function is associated with deficits in progenitor proliferation and cortical neuron content

Abstract: Transcription Factor 4 (TCF4) has been associated with autism, schizophrenia, and other neuropsychiatric disorders. However, how pathological TCF4 mutations affect the human neural tissue is poorly understood. Here, we derive neural progenitor cells, neurons, and brain organoids from skin fibroblasts obtained from children with Pitt-Hopkins Syndrome carrying clinically relevant mutations in TCF4. We show that neural progenitors bearing these mutations have reduced proliferation and impaired capacity to differe… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1
1

Citation Types

0
17
0

Year Published

2022
2022
2024
2024

Publication Types

Select...
6
1

Relationship

0
7

Authors

Journals

citations
Cited by 39 publications
(20 citation statements)
references
References 71 publications
0
17
0
Order By: Relevance
“…S8a ). In particular, some highly conserved TFs such as the regulator of neural stem cells tcf4 51 and the known neural developmental regulator lhx6 52 were detected in four species (Fig. S8a ).…”
Section: Resultsmentioning
confidence: 99%
“…S8a ). In particular, some highly conserved TFs such as the regulator of neural stem cells tcf4 51 and the known neural developmental regulator lhx6 52 were detected in four species (Fig. S8a ).…”
Section: Resultsmentioning
confidence: 99%
“…The most consistent phenotype we report across network development, using a variety of assays (Ca 2+ imaging, MEA, sEPSC frequency), is a deficit in network-wide neuronal spiking. Importantly, these phenotypes are consistent across human and mouse PTHS models 52,53 . However, we extended these findings by identifying several cellular and molecular mechanisms underlying the reduced network activity in these PTHS models.…”
Section: Discussionmentioning
confidence: 53%
“…TCF4 gene encodes a widely expressed class I basic helix-loop-helix (bHLH) transcription factor that has a critical role in the developing brain (de Pontual et al, 2009;Kim et al, 2020;Papes et al, 2022).…”
Section: Introductionmentioning
confidence: 99%
“…Haploinsufficient TCF4 neural progenitors have decreased capacity to proliferate and differentiate into neurons (Papes et al, 2022). Pitt-Hopkins syndrome (PTHS; MIM# 610954) is a neurodevelopmental condition caused by heterozygous pathogenic variants in TCF4 gene, with most variants arising de novo (Amiel et al, 2007).…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation