Cell-to-cell heterogeneity in Sox2 and Bra expression guides progenitor motility and destiny

eLife, Год журнала: 2021, Номер 10

Опубликована: Окт. 5, 2021

Although cell-to-cell heterogeneity in gene and protein expression within cell populations has been widely documented, we know little about its biological functions. By studying progenitors of the posterior region bird embryos, found that levels transcription factors Sox2 Bra, respectively involved neural tube (NT) mesoderm specification, display a high degree heterogeneity. combining forced downregulation approaches with time-lapse imaging, demonstrate Sox2-to-Bra ratio guides progenitor’s motility their ability to stay or exit progenitor zone integrate mesodermal tissues. Indeed, Bra confer pushes cells join paraxial mesoderm, while tend inhibit movement forcing NT. Mathematical modeling captures importance regulation this process further suggests randomness Sox2/Bra distribution favors rearrangements tissue shape conservation.

Язык: Английский

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A fishy tail: Insights into the cell and molecular biology of neuromesodermal cells from zebrafish embryos

Developmental Biology, Год журнала: 2022, Номер 487, С. 67 - 73

Опубликована: Май 2, 2022

Язык: Английский

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Chimeric 3D gastruloids – a versatile tool for studies of mammalian peri-gastrulation development

Development, Год журнала: 2022, Номер 149(22)

Опубликована: Ноя. 3, 2022

ABSTRACT Stem cell-derived three-dimensional (3D) gastruloids show a remarkable capacity of self-organisation and recapitulate many aspects gastrulation stage mammalian development. Gastruloids can be rapidly generated offer several experimental advantages, such as scalability, observability accessibility for manipulation. Here, we present approaches to further expand the potency murine 3D by using functional genetics in mouse embryonic stem cells (mESCs) generate chimeric gastruloids. In gastruloids, fluorescently labelled different genotypes harbouring inducible gene expression or loss-of-function alleles are combined with wild-type cells. We showcase this approach mESCs carrying homozygous deletions Tbx transcription factor brachyury Eomes. Resulting reported Eomes functions, instructing cardiac fate promoting posterior axial extension, respectively. Additionally, revealed previously unrecognised phenotypes, tissue sorting preference deficient endoderm cell non-autonomous effects deficiency on Wnt3a patterning along axis, demonstrating some advantages an efficient tool studies gastrulation.

Язык: Английский

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Capture of Human Neuromesodermal and Posterior Neural Tube Axial Stem Cells

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 29, 2024

ABSTRACT The spinal cord, nerves, and skeletal muscles arise from neuromesodermal progenitors (NMPs). We have developed a growth-factor screening strategy, utilizing ES iPS cells, facilitating the indefinite self-renewal of two types human axial stem cells (AxSCs), closely resembling mouse NMPs (NM-AxSCs) posterior neural tube (N-AxSCs). Under specific regimens— Wnt/CHIR99021, FGF2, TGF-β inhibitor SB431542 (CFS) excluding FGF2 (CS), respectively—these AxSCs self-renew sustain telomeres. Single cell transcriptomics proteomics revealed expression growth-zone dorsoventral markers in NM-AxSCs, correspondingly, differentiation to wide spectrum neurons myocytes. N-AxSCs rapidly matured into dorsal sensory subsets crest. Crucially, neither AxSC type produces teratomas, analogous NM-AxSCs integrated successfully somites. Capturing patient GMP / without transgenesis unveils ontogeny promises modeling therapy neuropathies.

Язык: Английский

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The ratio of Wnt signaling activity to Sox2 transcription factor levels predicts neuromesodermal fate potential

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 17, 2025

Abstract Neuromesodermal progenitors (NMPs) are a vertebrate cell type that contribute descendants to both the spinal cord and mesoderm. The undifferentiated bipotential NMP state is maintained when Wnt signaling active Sox2 present. We used transgenic reporter lines live-image activity levels in NMPs observed unique cellular ratio compared NMP-derived mesoderm or neural tissue. this signature identify previously unknown anatomical position of progenitor population gives rise midline tissues floor plate mesodermal notochord. Thus, quantification can be predict cells with neuromesodermal potential. also developed auxin inducible degron 2 system for use zebrafish test temporal role plays during formation. found ectopic presence holds plate/notochord state, degradation required adopt notochord fate.

Язык: Английский

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