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Transcriptome analysis of self-renewing human pancreatic progenitors derived from pluripotent stem cells

ABSTRACT: Transcriptome analysis of self-renewing human pancreatic progenitors derived from pluripotent stem cells

PROVIDER: PRJEB20752 | ENA |

REPOSITORIES: ENA

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Transcriptome analysis of self-renewing human pancreatic progenitors derived from pluripotent stem cells

Project description:Human pluripotent stem cells were differentiated into PDX1+/NKX6-1+ Pancreatic Progenitors (PPd15 cells), which were subsequently captured and expanded in culture. These culture Pancreatic Progenitors (cPP cells) were capable of self-renewal and could be passaged up to 20 times. Furthermore, cPP cells were capable of differentiation into multiple pancreatic lineages, including c-peptide+ beta-like cells, both in vitro and in vivo.

2017-06-06 | E-MTAB-5731 | biostudies-arrayexpress

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DPPIV+ fibro-adipogenic progenitors form the niche of adult skeletal muscle self-renewing resident macrophages

Project description:Depending on the tissue, adult tissue-resident macrophages (RMs) are either maintained by blood monocytes or through self-renewal at steady state. While the presence of a nurturing-niche is likely crucial to support the survival and function of self-renewing RMs, evidence regarding its nature is limited. Here, we aimed to characterize the niche for skeletal muscle RMs. We found stromal cells called Fibro-Adipogenic Progenitors (FAPs) to be the main source of colony-stimulating factor 1 (CSF1) in resting skeletal muscle. By utilizing parabiosis in combination with transgenic lines that deplete FAPs (PdgfrαCreERT2 ´ DTA) or conditionally delete FAP-derived CSF1 (PdgfrαCreERT2 ´ Csf1flox/null), we showed that local CSF1 from FAPs is required for the survival of both TIM4- monocyte-derived and TIM4+ self-renewing RMs at steady state in adult skeletal muscle. Following pharmacological depletion of RMs, local CSF1 increases significantly to facilitate their replenishment. Indeed, TIM4- RMs get replaced by blood monocytes following depletion and their numbers increase significantly beyond the normal levels. While a noticeable fraction of TIM4+ RMs also gets replaced by blood monocytes following depletion, their numbers are tightly controlled, which indicates the presence of regulatory mechanisms exclusive to TIM4+ cells. The spatial distribution and number of TIM4+ RMs match with a subpopulation of Dipeptidyl peptidase IV (DPPIV)+ FAPs, suggesting their role as nurturing CSF1-producing niche cells for self-renewing RMs. This finding offers novel opportunities to precisely manipulate the function of self-renewing RMs in situ to further unravel their role in health and disease.

2023-10-24 | GSE241832 | GEO

Long-Term Culture of Self-renewing Pancreatic Progenitors Derived from Human Pluripotent Stem Cells.

Project description: Not available

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Self-renewing human naïve pluripotent stem cells dedifferentiate in 3D culture and form blastoids spontaneously

Project description:Human naïve pluripotent stem cells (hnPSCs) can generate integrated models of blastocysts termed blastoids upon switch to inductive medium. However, the underlying mechanisms remain obscure. Here we report that self-renewing hnPSCs spontaneously and efficiently give rise to blastoids upon three dimensional (3D) suspension culture. The spontaneous blastoids mimic early stage human blastocysts in terms of structure, size, and transcriptome characteristics and are capable of progressing to post-implantation stages. This property is conferred by the glycogen synthase kinase-3 (GSK3) signalling inhibitor IM-12 present in 5iLAF self-renewing medium. IM-12 upregulates oxidative phosphorylation-associated genes that underly the capacity of hnPSCs to generate blastoids spontaneously. Starting from day one of self-organization, hnPSCs at the boundary of all 3D aggregates dedifferentiate into E5 embryo-like intermediates. Intermediates co-express SOX2/OCT4 and GATA6 and by day 3 specify trophoblast fate, which coincides with cavity and blastoid formation. In summary, spontaneous blastoid formation results from 3D culture triggering dedifferentiation of hnPSCs into earlier embryo-like intermediates which are then competent to segregate blastocyst fates.

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Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells

Project description:Self-renewing tissue-resident macrophages are thought to be exclusively derived from embryonic progenitors. However, whether circulating monocytes can also give rise to such macrophages has not been formally investigated. Here we use a new model of diphtheria toxin-mediated depletion of liver-resident Kupffer cells to generate niche availability and show that circulating monocytes engrafted in the liver, gradually adopt the transcriptional profile of their depleted counterparts and become long-lived self-renewing cells. Underlining the physiological relevance of our findings, circulating monocytes also contribute to the expanding pool of macrophages in the liver shortly after birth, when macrophage niches become available during normal organ growth. Thus, like embryonic precursors, monocytes can and do give rise to self-renewing tissue-resident macrophages if the niche is available to them.

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