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Neuronal lineage tracing from progenitors in human cortical organoids reveals mechanisms of neuronal production, diversity, and disease

ABSTRACT: Neuronal lineage tracing from progenitors in human cortical organoids reveals mechanisms of neuronal production, diversity, and disease

PROVIDER: PRJNA1160882 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30662300.fastq.gz	Fastqsanger.gz
	SRR30662301.fastq.gz	Fastqsanger.gz
	SRR30662302.fastq.gz	Fastqsanger.gz
	SRR30662303.fastq.gz	Fastqsanger.gz
	SRR30662304.fastq.gz	Fastqsanger.gz

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Neuronal lineage tracing from progenitors in human cortical organoids reveals mechanisms of neuronal production, diversity, and disease

Project description:The contribution of progenitor subtypes to generate the billions of neurons produced during human cortical neurogenesis is not well understood. We developed the Cortical ORganoid Lineage Tracing (COR-LT) system for human cortical organoids. Differential fluorescent reporter activation in distinct progenitor cells leads to permanent reporter expression, enabling the progenitor cell lineage of neurons to be determined. Surprisingly, nearly all excitatory neurons produced in cortical organoids were generated indirectly from intermediate progenitor cells, while astrocytes and inhibitory neurons were produced both directly and indirectly. Additionally, neurons of different progenitor lineages were transcriptionally distinct. Isogenic lines made from an autistic individual with and without a likely pathogenic variant in the CTNNB1 gene demonstrated that the variant substantially altered the proportion of neurons derived from specific progenitor cell lineages, as well as the lineage-specific transcriptional profiles of these neurons, suggesting a pathogenic mechanism for this mutation. These results suggest individual progenitor subtypes play unique roles in generating the diverse neurons of the human cerebral cortex.

2024-09-16 | GSE277159 | GEO

Individual Human Cortical Progenitors Can Produce Excitatory and Inhibitory Neurons

Project description:The cerebral cortex is a cellularly-complex structure comprised of a rich diversity of neuronal and glial cell types. Cortical neurons can be broadly categorized into two classes—glutamatergic excitatory neurons and GABAergic inhibitory interneurons. Previous developmental studies in rodents have led to the prevailing model that while excitatory neurons are born from progenitors located in the cortex, cortical interneurons are born from a separate population of progenitors located outside of the developing cortex in the ganglionic eminences1-5. However, the developmental potential of human cortical progenitors has not been thoroughly explored. Here we show that in addition to excitatory neurons and glia, human cortical progenitors are also capable of producing GABAergic neurons with the transcriptional characteristics and morphologies of cortical interneurons. By developing a cellular barcoding tool called “ScRNAseq-compatible Tracer for Identifying Clonal Relationships” (STICR), we were able to perform clonal lineage tracing of 1912 primary human cortical progenitors from six specimens and capture both the transcriptional identities and clonal relationships of their resulting progeny. A subpopulation of cortically-born GABAergic neurons were transcriptionally similar to cortical interneurons born from the caudal ganglionic eminence and these cells were frequently related to excitatory neurons and glia. Thus, our results demonstrate that individual human cortical progenitors can generate both excitatory neurons and cortical interneurons, providing a new framework for understanding the origins of neuronal diversity in the human cortex.

2021-11-06 | GSE187875 | GEO

Transcription profiling of rat neuronal progenitors obtained at embryonic day 11 (E11), E12 and E13 identifies an miRNA Regulatory network at the onset of rat neurogenesis

Project description:Cortical development is a complex process involving the generation of neuronal progenitors, which proliferate and migrate to form the stratified layers of the maturing cortex. To identify microRNAs (miRNAs) and genes that may be important during early cortical development, we analyzed the expression profiles of rat neuronal progenitors obtained at embryonic day 11 (E11), E12 and E13 using microarrays. Neuronal progenitors were purified from telencephalic dissociates with a positive-selection strategy using surface labeling tetanus-toxin and cholera-toxin and fluorescence-activated cell sorting. We identified classes of miRNAs and mRNAs that were up-regulated or down-regulated in these neuronal progenitors as cortical development progressed from E11 to E13. We present data that supports a regulatory role for miRNAs during the transition from neuronal progenitors into differentiating cortical neurons. Experiment Overall Design: Flow cytometry was used to isolate tetanus toxin+ and cholera toxin+ neuronal progenitors from embryonic days 11, 12 and 13 rat telencephalon. 4 biological replicates were obtained for each group using a pooled litters for each biological replicate on different prepararation days

2009-01-13 | E-GEOD-11334 | biostudies-arrayexpress

Identification of a miRNA Regulatory Network in FACS-Purified Neuronal Progenitors at the Onset of Rat Neurogenesis

2008-12-01 | GSE11334 | GEO

Cpeb3 knockout cortical neuronal cultures

Project description:Cpeb3 knockout cortical neuronal cultures

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Meningeal cells contribute to postnatal cortical neurogenesis.

Project description:Postnatal brain neurogenesis in mammals is believed to be restricted to rare germinative remnants of the neuroepithelium. In this study, we discovered that, in the postnatal brain, a subset of embryonically derived progenitors is present in meningeal substructures. These cells migrate from the meningeal substructures to the retrosplenial and visual motor cortex and differentiate into (electrically) functional integrated neurons. Lineage tracing analysis revealed that this subset of neural progenitors originate largely from PDGFR+ cells. PDGFR-derived cells differentiate mostly into Satb2+ neurons in cortical layers I-IV. Thus, a reservoir of embryonically derived progenitors in the meninges contributes to postnatal cerebral cortical neurogenesis.

2016-11-23 | E-MTAB-4951 | biostudies-arrayexpress

Isotope tracing analysis of stress erythroid progenitors

Project description:Isotope tracing analysis to study the intracellular metabolic changes of progenitors during the expansion stage of stress erythropoiesis and assess the effect of 1400w treatment.

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Charting the age-altered thymic epithelial cell differentiation by lineage tracing from a beta 5-t expressing TEC progenitor

Project description:TEC progenitors that express beta 5-t contribute to both the cortical and medullary TEC compartments. Our initial experiments across ageing thymi identified a population of potential progenitor TECs which expanded with age, and appears to be a progenitor population for mTEC. These lineage tracing experiments are designed to chart the altered differentiation and senescence of mTEC progenitors with age.

2020-09-14 | E-MTAB-8737 | biostudies-arrayexpress

Dual genetic lineage tracing reveals functional neuromesodermal progenitors

Project description:Dual genetic lineage tracing reveals functional neuromesodermal progenitors

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Gene expression profile of cerebral cortical cells after Rb family inactivation in progenitors and neurons

Project description:Cell cycle deregulation leads to abnormal proliferation and cell death in a context-specific manner. Cell cycle progression driven via Rb pathway forces neurons to undergo S-phase, resulting in cell death associated with the progression of neuronal degeneration. Nevertheless, some Rb- and Rb family (Rb, p107, and p130)-deficient differentiating neurons can proliferate and form tumors. Here, we found that differentiating cerebral cortical excitatory neurons underwent S-phase progression but not cell division after acute Rb family inactivation in differentiating neurons. However, the differentiating neurons underwent cell division and form tumors when Rb family members were inactivated in cortical progenitors. Differentiating neurons generated from Rb -/-; p107 -/-; p130 -/- (Rb-TKO) progenitors, but not acutely inactivated Rb-TKO differentiating neurons, activated DNA double-strand break (DSB) repair pathway without increasing the tri-methylation of histone H4 at lysine 20 (H4K20M3), which is known to protect from DNA damage. The activation of DSB repair pathway was essential for the cell division of Rb-TKO differentiating neurons. These results suggest that newly-born cortical neurons from progenitors epigenetically become protected from DNA damage and cell division in a Rb family-dependent manner. 3 samples of pCAG-control, pCAG-RbTKO, pMAP2-control, and pMAP2-RbTKO cells

2014-01-01 | E-GEOD-37577 | biostudies-arrayexpress

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