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Generation of self-renewing neuromesodermal progenitors with neuronal and skeletal muscle bipotential from human embryonic stem cells

ABSTRACT: Generation of self-renewing neuromesodermal progenitors with neuronal and skeletal muscle bipotential from human embryonic stem cells

PROVIDER: PRJNA1130495 | ENA |

REPOSITORIES: ENA

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Generation of self-renewing neuromesodermal progenitors with neuronal and skeletal muscle bipotential from human embryonic stem cells

Project description:Progress has been made in generating spinal cord and trunk derivatives from neuromesodermal progenitors (NMPs). However, maintaining the self-renewal of NMPs in vitro remains a challenge. In this study, we developed a cocktail of small molecules and growth factors that induces human embryonic stem cells to produce self-renewing NMPs (srNMPs) under chemically defined conditions. These srNMPs maintain the state of thoracic neuromesodermal progenitors in prolonged culture and have the bipotential to generate mesodermal cells and neurons, even at the single-cell level. Additionally, suspended srNMP aggregates could partially mimic the structural properties of early embryonic trunks. Furthermore, transplanted srNMP-derived muscle satellite cells or progenitors of motor neurons were integrated into skeletal muscle or the spinal cord, respectively, and contributed to regeneration in mouse models. In summary, srNMPs hold great promise for applications in developmental biology and as renewable cell sources for cell therapy for trunk and spinal cord injuries.

2025-01-11 | GSE271234 | GEO

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

Restrictive and extensively self-renewing erythroblast

Project description:Transcription profiles of self renewing erythroblast cultures isolated from both the restricted and extensively self-renewing phases of growth. The samples are paired.

2015-04-30 | E-MTAB-3112 | biostudies-arrayexpress

A self-renewing biomimetic skeletal muscle construct engineered using induced myogenic progenitor cells

Project description:Skeletal muscle is a highly organized and regenerative tissue that maintains its homeostasis primarily by activation and differentiation of muscle stem cells. Mimicking an in vitro skeletal muscle differentiation program that contains self-renewing adult muscle stem cells and aligned myotubes has been challenging. Here, we set out to engineer a biomimetic skeletal muscle construct that can self-regenerate and produce aligned myotubes using induced myogenic progenitor cells (iMPCs), a heterogeneous culture consisting of skeletal muscle stem, progenitor and differentiated cells. Utilizing electrospinning, we fabricated polycaprolactone (PCL) substrates that enabled iMPC-differentiation into aligned myotubes by controlling PCL fiber orientation. Newly-conceived constructs contained highly organized multinucleated myotubes in conjunction with self-renewing muscle stem cells, whose differentiation capacity was augmented by Matrigel supplementation. Additionally, we demonstrate using single cell RNA sequencing (scRNA-seq) that iMPC-derived constructs faithfully recapitulate a step-wise myogenic differentiation program. Notably, when the constructs were subjected to a damaging myonecrotic agent, self-renewing muscle stem cells rapidly differentiated into aligned myotubes, akin to skeletal muscle repair in vivo. Taken together, we report on a novel in vitro system that mirrors myogenic regeneration and muscle fiber alignment, and can serve as a platform to study myogenesis, model muscular dystrophies or perform drug screens.

2023-09-27 | GSE222162 | GEO

SCL and LMO1 reprogram thymocytes into self-renewing cells.

Project description:The SCL and LMO1 oncogenic transcription factors reprogram thymocytes into self-renewing pre-leukemic stem cells (pre-LSCs). Here we report that SCL directly interacts with LMO1 to activate the transcription of a self-renewal program coordinated by LYL1. Gene expression profiles of thymocytes from SCL-LMO1 transgenic and age-matched non transgenic Cd3Îµ-/- mice were compared to identify candidate genes that confer self-renewal capability to pre-leukemic thymocytes.

2015-11-05 | E-GEOD-74659 | biostudies-arrayexpress

SCL and LMO1 reprogram thymocytes into self-renewing cells.

2015-11-05 | GSE74659 | GEO

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

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

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Thy-1 Expression Enriches for Self-Renewing Murine MRUs

Project description:Thy-1 Expression Enriches for Self-Renewing Murine MRUs

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

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

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A Hierarchy of Self-Renewing Tumor-Initiating Cell Types in Glioblastoma

Project description:The neural stem cell marker CD133 is reported to identify cells within glioblastoma (GBM) that can initiate neurosphere growth and tumor formation, however, instances of CD133- cells exhibiting similar properties have also been reported. Here, we show that some PTEN-deficient GBM tumors produce a series of CD133+ and CD133- self-renewing tumor-initiating cell types and provide evidence that these cell types constitute a lineage hierarchy. Our results show that the capacities for self-renewal and tumor initiation in GBM need not be restricted to a uniform population of stem-like cells, but can be shared by a lineage of self-renewing cell types expressing a range of markers of forebrain lineage. Keywords: Expression and copy number analysis of glioblastomas and neurosphere forming derivative cell lines of same.

2010-04-22 | GSE19612 | GEO

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