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Characterization of Mfsd2a-deficient lung AT2 cells.

ABSTRACT: Characterization of Mfsd2a-deficient lung AT2 cells.

PROVIDER: PRJNA772766 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16490881_1.fastq.gz	Fastqsanger.gz
	SRR16490881_2.fastq.gz	Fastqsanger.gz
	SRR16490882_1.fastq.gz	Fastqsanger.gz
	SRR16490882_2.fastq.gz	Fastqsanger.gz
	SRR16490883_1.fastq.gz	Fastqsanger.gz

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Characterization of Mfsd2a-deficient lung AT2 cells.

Project description:RNA-seq was performed to understand transcriptome changes with Mfsd2a deficiency in lung AT2 cells. Gene expression analysis was performed using DESeq2.

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Comparison of wild-type and Mfsd2a KO eye cups

Project description:Eye photoreceptor membrane discs in outer rod segments are highly enriched in the visual pigment rhodopsin and the omega-3 fatty acid docosahexaenote (DHA). The eye acquires DHA from blood, but transporters for DHA uptake across the blood-retinal barrier (BRB) or retinal pigment epithelium have not been identified. Mfsd2a is a newly described sodium-dependent lysophosphatidylcholine symporter expressed at the BRB. Microarrays were used to determine difference in gene expression between wild-type and Mfsd2a KO eye cups. RNA was extracted from eye cups from postnatal day 13 wild-type and Mfsd2a KO mice. Equal amounts of RNA from 6 wild-type eye cups were pooled for the wild-type sample, or 6 Mfsd2a KO eye cups were pooled for the Mfsd2a KO sample. Microarray profiling was done on pooled samples with a RIN cut-off of 7.0 using Mouse 430 2.0 arrays (Affymetrix).

2016-03-23 | E-GEOD-77403 | biostudies-arrayexpress

Transcriptional profiling of CD44hi AT2 cells under homeostasis and after lung injury [II]

Project description:The epithelium of alveoli is composed of alveoli type I cells (AT1) that cover ~95% of the surface area and alveoli type II cells (AT2) that secret surfactant as well as function as adult stem cells. CD44hi subpopulation of AT2 cells exhibits higher potential to proliferate and differentiate under steady state conditions. To understand the CD44hi subpopulation of AT2 cells after lung injury, we assessed those cells in a Pseudomonas aeruginosa (PA) induced mouse model of lung injury. CD44hi and CD44low AT2 cells were FACS sorted from untreated and 3d PA treated mice. In addition, since Sca1+ AT2 cells were shown to emerge during the repair phase of the PA induced injury in our earlier studies, we also isolated Sca1+ AT2 cells at 3d post PA injury to compare with the CD44hi subpopulation. RNA-seq was used to compare the expression profile of the different subgroups of AT2 cells.

2024-05-23 | GSE267236 | GEO

Etv5 ChIP-seq in AT2 cells

Project description:Alveolar type II (AT2) cell dysfunction contributes to a number of significant human pathologies including respiratory distress syndrome, lung adenocarcinoma, and debilitating fibrotic diseases, but the critical transcription factors that maintain AT2 cell identity are unknown. Here we show that the E26 transformation-specific (ETS) family transcription factor Etv5 is essential tomaintain AT2 cell identity. Deletion of Etv5 from AT2 cells produced gene and protein signatures characteristic of differentiated alveolar type I (AT1) cells. Consistent with a defect in the AT2 stem cell population, Etv5 deficiency markedly reduced recovery following bleomycin-induced lung injury. Lung tumorigenesis driven by mutant KrasG12D was also compromised by Etv5 deficiency. ERK activation downstream of Ras was found to stabilize Etv5 through inactivation of the cullin- RING ubiquitin ligase CRL4COP1/DET1 that targets Etv5 for proteasomal degradation. These findings identify Etv5 as a critical output of Ras signaling in AT2 cells, contributing to both lung homeostasis and tumor initiation.

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Human lung AT2 cell organoids infected with CoV-2, treated with inhibitors

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Transcriptional profiling of CD44hi AT2 cells under homeostasis and after lung injury [I]

Project description:The epithelium of alveoli is composed of alveoli type I cells (AT1) that cover ~95% of the surface area and alveoli type II cells (AT2) that secret surfactant as well as function as adult stem cells. To characterize a subgroup of AT2 that express higher levels of hyaluronan receptor CD44 (the CD44high, or CD44hi AT2) and behave as alveoli epithelial stem cells during steady-state homeostasis, we used RNA-sequencing to compare the expression profiles of these cells with the bulk CD44low (or CD44lo ) AT2. CD44hi AT2 showed gene signatures that indicate partial de-differentiation and a higher potential to proliferate compared with CD44lo AT2. At steady-state conditions, CD44hi AT2 also showed higher expression of genes activated by NFκB mediated inflammatory responses and transcriptome signatures that resemble early-stage Kras-induced adenocarcinoma. Furthermore, these cells were more responsive to KrasG12D induction both in 3D tumor organoid culture and in mouse lung cancer cell transplantation models. In summary, CD44hi AT2 plays an essential role in the homeostatic maintenance of the alveolar epithelium and tumor initiation.

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Study of vascular endothelial-specific and inducible vascular endothelial-specific deletion of Major Facilitator Superfamily Domain containing 2a (Mfsd2a) in mice.

Project description:Brain development requires a massive increase in brain lipogenesis and accretion of the essential omega-3 fatty acid docosahexaenoic acid (DHA). Brain acquisition of DHA is primarily mediated by the transporter Major Facilitator Superfamily Domain containing 2a (Mfsd2a) expressed in the endothelium of the blood-brain barrier. Mfsd2a transports DHA and other polyunsaturated fatty acids esterified to lysophosphatidylcholine (LPC-DHA). However, the function of Mfsd2a and DHA in brain development is incompletely understood. Using vascular endothelial-specific (2aECKO) and inducible vascular endothelial-specific (2aiECKO) deletion of Mfsd2a in mice, we found Mfsd2a to be uniquely required postnatally at the blood-brain barrier for normal brain growth and DHA accretion, with DHA deficiency preceding the onset of microcephaly. Gene expression profiling analysis of these DHA deficient brains indicated that Srebp-1 and Srebp-2 pathways were highly elevated. Affymetrix gene arrays were used to determine differences in gene expression between 2aECKO or 2aiECKO relative to their respective controls in the developing brain.

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