The ratio of Wnt signaling activity to Sox2 transcription factor levels predicts neuromesodermal fate potential DOI Creative Commons
Robert D. Morabito, David Tatarakis,

Robert W. Swick

и другие.

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

Zebrahub – Multimodal Zebrafish Developmental Atlas Reveals the State-Transition Dynamics of Late-Vertebrate Pluripotent Axial Progenitors DOI Creative Commons
Merlin Lange, Alejandro Granados, Shruthi VijayKumar

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Март 7, 2023

ABSTRACT Elucidating the developmental processes of organisms requires a comprehensive understanding cellular lineages in spatial, temporal, and molecular domains. In this study, we introduce Zebrahub, dynamic atlas zebrafish embryonic development that integrates single-cell sequencing time course data with lineage reconstructions facilitated by light-sheet microscopy. This offers high-resolution in-depth insights into development, achieved through individual embryos across ten stages, complemented trajectory reconstructions. Zebrahub also incorporates an interactive tool to navigate complex flows derived from microscopy data, enabling silico fate mapping experiments. To demonstrate versatility our multi-modal resource, utilize provide fresh pluripotency Neuro-Mesodermal Progenitors (NMPs). Our publicly accessible web-based platform, is foundational resource for studying at both transcriptional spatiotemporal levels, providing researchers integrated approach exploring analyzing complexities during embryogenesis.

Язык: Английский

Процитировано

54

Controlling organoid symmetry breaking uncovers an excitable system underlying human axial elongation DOI Creative Commons
Giridhar M. Anand,

Heitor C. Megale,

Sean H. Murphy

и другие.

Cell, Год журнала: 2023, Номер 186(3), С. 497 - 512.e23

Опубликована: Янв. 18, 2023

Язык: Английский

Процитировано

49

Controlling human organoid symmetry breaking reveals signaling gradients drive segmentation clock waves DOI Creative Commons
Yusuf Ilker Yaman, Sharad Ramanathan

Cell, Год журнала: 2023, Номер 186(3), С. 513 - 527.e19

Опубликована: Янв. 18, 2023

Язык: Английский

Процитировано

46

Statistically derived geometrical landscapes capture principles of decision-making dynamics during cell fate transitions DOI Creative Commons
Meritxell Sáez, Robert Blassberg, Elena Camacho-Aguilar

и другие.

Cell Systems, Год журнала: 2021, Номер 13(1), С. 12 - 28.e3

Опубликована: Сен. 17, 2021

Fate decisions in developing tissues involve cells transitioning between discrete cell states, each defined by distinct gene expression profiles. The Waddington landscape, which the development of a is viewed as ball rolling through valley filled terrain, an appealing way to describe differentiation. To construct and validate accurate landscapes, quantitative methods based on experimental data are necessary. We combined principled statistical with framework catastrophe theory approximate Bayesian computation formulate dynamical landscape that accurately predicts fate outcomes pluripotent stem exposed different combinations signaling factors. Analysis revealed two ways make binary choice one fates. suggest these represent archetypal designs for developmental decisions. approach broadly applicable analysis differentiation determining logic

Язык: Английский

Процитировано

104

Axial elongation of caudalized human organoids mimics aspects of neural tube development DOI Open Access
Ashley R.G. Libby, David Joy, Nicholas Elder

и другие.

Development, Год журнала: 2021, Номер 148(12)

Опубликована: Июнь 15, 2021

Axial elongation of the neural tube is crucial during mammalian embryogenesis for anterior-posterior body axis establishment and subsequent spinal cord development, but these processes cannot be interrogated directly in humans as they occur post-implantation. Here, we report an organoid model extension derived from human pluripotent stem cell (hPSC) aggregates that have been caudalized with Wnt agonism, enabling them to recapitulate aspects morphological temporal gene expression patterns development. Elongating organoids consist largely neuroepithelial compartments contain TBXT+SOX2+ neuro-mesodermal progenitors addition PAX6+NES+ progenitors. A critical threshold agonism stimulated singular axial extensions while maintaining multiple lineages, such displayed regionalized anterior-to-posterior HOX hindbrain (HOXB1) regions spatially distinct brachial (HOXC6) thoracic (HOXB9) regions. CRISPR interference-mediated silencing TBXT, a pathway target, increased compartmentalization, abrogated disrupted uniaxial elongation. Together, results demonstrate potent capacity hPSC undergo manner can used dissect cellular organization patterning decisions dictate early nervous system

Язык: Английский

Процитировано

72

Gastruloids: Pluripotent stem cell models of mammalian gastrulation and embryo engineering DOI Creative Commons
Alfonso Martínez Arias, Yusuke Marikawa, Naomi Moris

и другие.

Developmental Biology, Год журнала: 2022, Номер 488, С. 35 - 46

Опубликована: Май 7, 2022

Язык: Английский

Процитировано

47

Self-organizing models of human trunk organogenesis recapitulate spinal cord and spine co-morphogenesis DOI
Simona Gribaudo,

Rémi Robert,

Björn van Sambeek

и другие.

Nature Biotechnology, Год журнала: 2023, Номер 42(8), С. 1243 - 1253

Опубликована: Сен. 14, 2023

Язык: Английский

Процитировано

41

Notochord and axial progenitor generation by timely BMP and NODAL inhibition during vertebrate trunk formation DOI Creative Commons
Tiago Rito, Ashley R.G. Libby, Madeleine Demuth

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Фев. 28, 2023

Abstract The formation of the vertebrate body involves coordinated and progressive production trunk tissues from progenitors located in posterior embryo. In vitro models based on pluripotent stem cells (PSCs) replicate aspects this process, but they lack some tissue components normally present trunk. Most strikingly, notochord, a hallmark chordates source midline signals that pattern surrounding tissues, is absent current human formation. To investigate how formed, we performed single-cell transcriptomic analysis chick embryos. This delineated molecularly discrete progenitor populations, which spatially locate embryo, compare across species, relate to signalling activity. Guided by map, determined differentiating PSCs develop stereotypical spatial organization types. We found LATS1/2 repression YAP activity, conjunction with FGF-mediated MAPK activation, induced transcription factor Bra/TBXT facilitated WNT signaling. addition, inhibiting WNT-induced NODAL BMP signaling cascade at appropriate time regulated proportions different types produced, including notochordal cells. used information create an integrated 3D model gastrulation undergoing morphogenetic movements produce elongated structures notochord patterned neural Together data provide insight into mechanisms responsible for comprise pave way future studies patterning tissue-like environment.

Язык: Английский

Процитировано

24

Notch signalling influences cell fate decisions and HOX gene induction in axial progenitors DOI Creative Commons
Fay Cooper,

Céline Souilhol,

Scott Haston

и другие.

Development, Год журнала: 2024, Номер unknown

Опубликована: Янв. 15, 2024

The generation of the post-cranial embryonic body relies on coordinated production spinal cord neurectoderm and presomitic mesoderm cells from neuromesodermal progenitors (NMPs). This process is orchestrated by pro-neural pro-mesodermal transcription factors that are co-expressed in NMPs together with Hox genes, which critical for axial allocation NMP derivatives. reside a posterior growth region, marked expression Wnt, FGF Notch signalling components. While importance Wnt influencing induction differentiation well established, precise role remains unclear. Here, we show Wnt/FGF-driven human stem (hESCs) signalling. Using hESC-derived chick embryo grafting, demonstrate directs character at expense neural fate. We also contributes to activation HOX gene NMPs, partly non-cell-autonomous manner. Finally, provide evidence exerts its effects via establishment negative feedback loop

Язык: Английский

Процитировано

14

A multimodal zebrafish developmental atlas reveals the state-transition dynamics of late-vertebrate pluripotent axial progenitors DOI Creative Commons
Merlin Lange, Alejandro Granados, Shruthi VijayKumar

и другие.

Cell, Год журнала: 2024, Номер 187(23), С. 6742 - 6759.e17

Опубликована: Окт. 24, 2024

Язык: Английский

Процитировано

13