Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PRDM16 cooperates with LHX2 to shape the human brain

ABSTRACT: In the developing mouse brain, PRDM16 exhibits robust expression in radial glia (RG) progenitors, serving as one of the conserved core RG genes shared between humans and mice. Much is known regarding the functions of PRDM16 in the developing mouse brain, yet its roles in the developing human brain are less explored. Our study was motivated by detecting a patient with a de novo nonsense mutation in PRDM16 exhibiting lissencephaly and microcephaly features. We introduced the mutation in human stem cells in both homozygous and heterozygous manner and generated human cortical organoids. The organoids differed in cell cycle parameters, and RNA-seq demonstrated changes in cell adhesion and WNT-signaling, which were confirmed by immunostaining. We further generated ChIP-seq data from human fetuses and compared the results to ChIP-seq data previously obtained from mice and differentially expressed genes in humans and mice (REFS he and baizabal papers). The top detected motif matched LHX2, so we compared our data with recently acquired LHX2 ChIP-seq data from the mouse. Our studies show highly conserved genes and pathways suggesting that PRDM16 and LHX2 complex and collaborate in the developing mouse and human brains. The multifaceted nature of PRDM16 and its intricate involvement in transcriptional regulation and various developmental processes highlight its importance in understanding neurodevelopmental mechanisms.

ORGANISM(S): Homo sapiens

PROVIDER: GSE239855 | GEO | 2024/12/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

PRDM16 regulates a temporal transcriptional program to promote progression of cortical neural progenitors

Project description:Radial glia (RG) in the neocortex sequentially generate distinct subtypes of projection neurons, accounting for the diversity and complex assembly of cortical neural circuits. Mechanisms that drive the rapid and precise temporal progression of RG are beginning to be elucidated. Here we reveal that the RG-specific transcriptional regulator PRDM16 promotes the transition of early to late phase of neurogenesis in the mouse neocortex. Loss of Prdm16 delays the timely progression of RG, leading to defective cortical laminar organization. Our genomic analyses demonstrate that PRDM16 regulates a subset of genes that are dynamically expressed between early and late neurogenesis. We show that PRDM16 suppresses target gene expression through limiting chromatin accessibility of permissive enhancers. We further confirm that critical target genes regulated by PRDM16 comprise neuronal specification genes, cell cycle regulators and molecules required for neuronal migration. These findings provide evidences to support that neural progenitors temporally shift gene expression program to achieve neural cell diversity.

2021-03-03 | GSE162854 | GEO

Transcriptional networks identify synaptotagmin-like 3 as a regulator of cortical neuronal migration during early neurodevelopment

Project description:Human brain development is a complex process involving neural proliferation, differentiation, and migration which are directed by many essential cellular factors and drivers. Here, using the NetBID2 algorithm and developing human brain RNA sequencing(RNA-Seq) dataset, we identified synaptotagmin-like 3(SYTL3) as one of the top drivers of early human brain development. Interestingly, SYTL3 exhibited high activity but low expression in both early developmental human cortex and human embryonic stem cell(hESC)-derived neurons. Knockout of SYTL3(SYTL3 -KO) in human neurons or knockdown of Sytl3 in embryonic mouse cortex markedly promoted neuronal migration. Besides, SYTL3-KO caused an abnormal distribution of deep-layer neurons in brain organoids and reduced presynaptic neurotransmitter release in hESC-derived neurons. We further demonstrated that SYTL3-KO- accelerated neuronal migration was modulated by high expression of matrix metalloproteinases. Together, based on bioinformatics and biological experiments, we identified SYTL3 as a novel regulator of cortical neuronal migration in human and mouse developing brains.

2021-02-07 | E-MTAB-10058 | biostudies-arrayexpress

Human iPSC-derived cerebral organoids reveal progenitor pathology in EML1-linked cortical malformation

Project description:We report the single-cell RNA sequencing of day 33±2 human iPSC derived cerebral organoids harboring a CRIPSR/CAS9 mediated, heterozygous knock-out of the gene EML1 or the respective isogenic control organoids. By microdissection of several ventricular zones per organoid from 3 different batches followed by dissociation into single cells we obtained transcriptomic data of several thousand cells and we were able to identify different cell populations including RG cells (RG1), RG cells transitioning to bRG cells (RG to bRG), RG cells transitioning to neurons (RG2), intermediate progenitors and young neurons based on known marker genes (Nowakowski et al., 2017; Fan et al., 2020; Velasco et al., 2019; Pollen et al., 2015; Liu et al., 2017). When comparing the cell type composition between EML1-heKO and isogenic control-derived organoids we found a clear decrease of RG1 cells and a striking increase in the abundance of RG to bRG cells in the EML1-heKO condition, while only minor variations in the other cell clusters were observed. We further investigated molecular characteristics of the EML1-heKO derived RG to bRG cluster compared to control. Here we found a set of differentially expressed genes in the EML1-heKO compared to control. When further investigating these genes, we identified a clear upregulation of ECM and bRG markers Our data suggest that the RG to bRG cell cluster in the EML1-heKO is composed of a rather perturbed progenitor population not found as such in control organoids and most likely not reflecting a cell population present during normal human brain development.

2022-01-31 | GSE195666 | GEO

Architectural niche organization by LHX2 is linked to hair follicle stem cell function

Project description:To identify direct LHX2 target genes in HFSCs, we performed chromatin immunoprecipitation and deep sequencing (ChIP-seq) analysis using FACS-isolated HFSCs. Three independent LHX2 ChIP-seq experiments were conducted.

2013-09-05 | E-GEOD-48068 | biostudies-arrayexpress

Combination of a microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids

Project description:Brain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix (BEM) to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids. A three-dimensional culture modified with BEM significantly enhanced neurogenesis in developing brain organoids from human induced pluripotent stem cells. Cortical layer development, volumetric augmentation, and electrophysiological function of human brain organoids were further improved in a reproducible manner by dynamic culture in microfluidic chamber devices. Our engineering concept of reconstituting brain-mimetic microenvironments facilitates the development of a reliable culture platform for brain organoids, enabling effective modeling and drug development for human brain diseases.

2021-06-02 | PXD025397 | Pride

Organoids-on-a-chip for Colorectal Cancer and in Vitro Screening of Chemotherapeutic Drugs

Project description:The individualized treatment of tumors has always been an urgent problem in clinical practice. Organoids-on-a-chip can reflect the heterogeneity of tumors and is a good model for in vitro anticancer drug screening. In this study, surgical specimens of patients with advanced colorectal cancer will be collected for organoid culture and organoids-on-a- chip. Use organoids-on-a-chip to screen tumor chemotherapy drugs, compare the results of patients’ actual medication regimens, and study the guiding role of organoids in the formulation of precise tumor treatment plans. The investigators will compare the response of organoids to drugs in vitro with the patient’s response to actual chemotherapy and targeted drugs and explore the feasibility and accuracy of organoids-on-a-chip based drug screening for advanced colorectal cancer. The project will establish a screening platform for chemotherapeutic drugs and targeted drugs based on colorectal cancer organoids to quickly and accurately formulate personalized treatment plans for clinical patients.

| 2385953 | ecrin-mdr-crc

Mus musculus

Project description:Lhx2 ChIP-chip from primary mouse keratinocytes

| PRJNA147853 | ENA

Cistromic and epigenomic changes in Prdm16 knock-out brown adipose tissue

Project description:Prdm16 is a transcription factor that drives a complete program of brown adipocyte differentiation, but the mechanism by which Prdm16 activates gene transcription remains unknown. Utilizing ChIP-seq teqhnique, we found that Prdm16 binds to chromatin at/near many brown fat-selective genes in BAT. Interestingly, Prdm16-deficiency dramatically reduced the binding of Med1 to Prdm16-target sites. Indeed, Prdm16 binds and recruits Med1 to BAT-enriched genes and the loss of Prdm16 caused a fundamental change in chromatin architecture at key BAT-selective genes and also reduced transcirptional activity. Moreover, Prdm16, through its interaction with Med1, defines and regulates the activity of super-enhancers that drive the expression of cell identity genes. Together, these data demonstrate that Prdm16 drives gene transcription by recruiting Med1 to control chromatin architecture and super-enhancers. Brown adipose tissues were collected from Prdm16 knockout and wiletype 9-month-old mice and ChIP-seq was performed for Prdm16, PolII, Med1, and H3K27ac.

2015-02-10 | E-GEOD-63965 | biostudies-arrayexpress

Project description:Transcriptome profiles of Lhx2 knockout developing mouse gonads

| PRJNA936098 | ENA

Lhx2 ChIP-chip from primary mouse keratinocytes

Project description:The Lhx2 transcription factor plays essential roles in morphogenesis and patterning of ectodermal derivatives, as well as in controlling stem cell activity. Lhx2 is expressed in the hair follicle (HF) buds, while in postnatal telogen HFs Lhx2+ cells reside in the stem cell-enriched epithelial compartments (bulge, secondary hair germ) and co-express selected stem cell markers (Sox9, Tcf4 and Lgr5). Lhx2+ cells represent the vast majority of cells in the bulge and secondary hair germ that proliferate in response to skin injury. This is functionally important, since the wound re-epithelialization is significantly retarded in heterozygous Lhx2 knockout (+/-) mice, while anagen onset in the HFs located closely to the wound is accelerated compared to wild-type mice. Cell proliferation in the bulge and the number of Sox9+ and Tcf4+ cells in the HFs closely adjacent to the wound in Lhx2+/- mice are decreased in comparison to wild-type controls, while expression of Lgr5 and cell proliferation in the secondary hair germ are increased. Furthermore, acceleration of wound-induced anagen development in Lhx2+/- mice is inhibited by administration of Lgr5 siRNA. In addition, Chip-on-chip/ChIP-qPCR and reporter assay analyses reveal Sox9, Tcf4 and Lgr5 as direct Lhx2 targets in keratinocytes. These data strongly suggest that Lhx2 positively regulates Sox9 and Tcf4 in the bulge cells and promotes wound re-epithelization, while it simultaneously negatively regulates Lgr5 in the secondary hair germ and inhibits HF cycling. Thus, Lhx2 operates as a regulator of epithelial stem cell activity during skin response to injury. Chromatin form primary mouse keratinocytes (PMK) was subjected to ChIP analysis with Lhx2 antibody; input and ChIP DNA were labelled with Cy3 and Cy5 respectivly and used form Nimblegen MM8 Mouse Promoter Array

2011-10-03 | E-GEOD-32514 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data