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Expansion of adult human pancreatic tissue yields organoids harbouring progenitor cells with endocrine differentiation potential

ABSTRACT: Expansion of adult human pancreatic tissue yields organoids harbouring progenitor cells with endocrine differentiation potential

PROVIDER: PRJNA428952 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6449570_1.fastq.gz	Fastqsanger.gz
	SRR6449570_2.fastq.gz	Fastqsanger.gz
	SRR6449580_1.fastq.gz	Fastqsanger.gz
	SRR6449580_2.fastq.gz	Fastqsanger.gz
	SRR6449571_1.fastq.gz	Fastqsanger.gz

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Expansion of adult human pancreatic tissue yields organoids harbouring progenitor cells with endocrine differentiation potential

Project description:Gene expression profiles from ALDH high cells sorted from expanded adult human pancreatic organoids are more similar to fetal pancreatic tissue and ALDH high cells sorted from expanded fetal human pancreatic organoids than to adult human islets or adult islet-depleted exocrine tissue.

2019-01-08 | GSE108854 | GEO

Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential.

Project description:Generating an unlimited source of human insulin-producing cells is a prerequisite to advance β cell replacement therapy for diabetes. Here, we describe a 3D culture system that supports the expansion of adult human pancreatic tissue and the generation of a cell subpopulation with progenitor characteristics. These cells display high aldehyde dehydrogenase activity (ALDHhi), express pancreatic progenitors markers (PDX1, PTF1A, CPA1, and MYC), and can form new organoids in contrast to ALDHlo cells. Interestingly, gene expression profiling revealed that ALDHhi cells are closer to human fetal pancreatic tissue compared with adult pancreatic tissue. Endocrine lineage markers were detected upon in vitro differentiation. Engrafted organoids differentiated toward insulin-positive (INS+) cells, and circulating human C-peptide was detected upon glucose challenge 1 month after transplantation. Engrafted ALDHhi cells formed INS+ cells. We conclude that adult human pancreatic tissue has potential for expansion into 3D structures harboring progenitor cells with endocrine differentiation potential.

| S-EPMC5918840 | biostudies-literature

Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses

Project description:Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses

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RNAseq: Elacestrant demonstrates strong anti-estrogenic activity in PDX models of estrogen- receptor positive endocrine-resistant and fulvestrant-resistant breast cancer

Project description:We carried out a comparative study of the orally bioavailable investigational SERD elacestrant, versus fulvestrant, in models of endocrine sensitive and resistant BC harbouring varying genetic backgrounds. Both drugs showed comparable effects on tumour growth of ER+ patient-derived xenograft models harbouring several ESR1 mutations and elacestrant showed activity after acquired resistance to fulvestrant. Treatment with either drug showed similar impact on ER-cistrome, ER- interactome and suppression of estrogen-regulated genes, confirming the anti-estrogenic activity of elacestrant.

2022-08-01 | GSE190384 | GEO

ChIP-seq: Elacestrant demonstrates strong anti-estrogenic activity in PDX models of estrogen- receptor positive endocrine-resistant and fulvestrant-resistant breast cancer

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The Swi/Snf chromatin remodeling complex regulates pancreatic endocrine cell expansion and differentiation in vivo

Project description:The Swi/Snf chromatin remodeling complex regulates pancreatic endocrine cell expansion and differentiation in vivo

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The Swi/Snf chromatin remodeling complex regulates pancreatic endocrine cell expansion and differentiation in vivo

Project description:Strategies to augment functional β-cell mass include directed differentiation of stem cells towards a β-cell fate, which requires extensive knowledge of transcriptional programs governing endocrine progenitor cell differentiation in vivo. Here we describe the contributions of the Brg1 and Brm ATPase subunits of the Swi/Snf chromatin remodeling complex on endocrine cell development. Through the use of transgenic knockout animal models we reveal that conditional knockout of Brg1 in endocrine progenitors results in blood glucose dysregulation, reduced islet mass and function, while loss of all Swi/Snf activity (Brg1 and Brm) results in early postnatal death, resulting from severe hyperglycemia and reduced β-cell mass. Single-cell RNA Sequencing of embryonic day 15.5 lineage-labeled cells revealed reduced expression of maturation markers, proliferation genes, and hormones in endocrine-committed, β- and α-cell clusters, highlighting a critical role for Swi/Snf in governing gene-expression programs essential for endocrine cell development.

2024-05-31 | GSE248369 | GEO

Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses (Experiment 2: scRNA-seq)

Project description:Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses (Experiment 2: scRNA-seq)

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Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses (Experiment 1: RNA-seq)

Project description:Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses (Experiment 1: RNA-seq)

| PRJNA490176 | ENA

Insulin deficiency distorts human pancreatic endocrine cell composition during development

Project description:Objective: The developmental effects of mutations in genes associated with monogenic diabetes on human pancreas development is not well understood. More specifically, if insulin gene recessive mutations influence the human endocrine lineage segregation still needs to be investigated. Methods: We generated a novel knock-in H2B-Cherry reporter human induced pluripotent stem cell (iPSCs) line expressing no insulin upon differentiation to stem cell-derived (SC-) β cells in vitro. This cell line enabled us to have a model mimicking the extremely reduced insulin levels in patients with recessive insulin mutations. We combined immunostaining, Western blotting and proteomics analysis to characterize the SC-islets from this iPSC line. Furthermore, we leveraged FACS analysis and imaging to explore the impact of insulin shortage on human endocrine cell induction, composition and proliferation. Results: We found that lack of insulin hampers insulin receptor (IR) signaling in SC-islets but increases the IR sensitivity. Furthermore, insulin deficiency showed no effects on human endocrine lineage induction. However, lack of insulin skewed the SC-islet cell composition. We found an increased in SC-β cell number at the expense of SC-α cell differentiation in the absence of insulin. Finally, insulin shortage reduced the rate of SC-β cell proliferation but had no impact of the expansion of SC-α cells. Conclusions: We provided evidence of the developmental impacts of reduced insulin levels on human β cell characteristics and endocrine lineage formation. These findings help to better understand the pathomechanisms of recessive insulin mutations during embryonic development and also shed some lights on the possible physiological function of this hormone coordinating human islet cell composition and architecture during endocrinogenesis.

2024-01-17 | PXD045366 | Pride

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