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Development Special Issue: Modelling Development in vitro

Volume 149, Issue 20
October 2022


A renaissance for developmental biology driven by new in vitro platforms
James M. Wells


Approaches to investigating metabolism in human neurodevelopment using organoids: insights from intestinal and cancer studies
Alexandria Morales,Madeline G. Andrews
Summary: This Spotlight discusses how findings in intestinal and cancer organoids could be applied to neural organoid models to probe metabolic changes during human neurodevelopment.

Lessons from early life: understanding development to expand stem cells and treat cancers
Fiona M. Bain,James L. C. Che,Maria Jassinskaja,David G. Kent
Summary: This Spotlight summarises how our understanding of haematopoietic development in vivo can be applied to expand haematopoietic stem cells in vitro and aid our understanding of the development, and possible treatment, of blood cancers.

Approaches to benchmark and characterize in vitro human model systems
Charlie J. Childs,Madeline K. Eiken,Jason R. Spence
Summary: This Spotlight discusses technological advances that have increased the field's understanding of human development and how these new findings are being leveraged to improve in vitro model systems.

In vitro models of human development and their potential application in developmental toxicity testing
Mirjam Niethammer,Tanja Burgdorf,Elisa Wistorf,Gilbert Schönfelder,Mandy Kleinsorge
Summary: Emerging in vitro models of human development, such as blastoids, gastruloids and organoids, could be applied in prospective developmental toxicity testing, provided they are thoroughly validated and meet regulatory approval.


Human assembloids
Sabina Kanton,Sergiu P. Paşca
Summary: This Development at a Glance article gives an overview of the potential of assembloids – three-dimensional, self-organizing in vitro cell culture systems constructed by integrating organoids or organoids and other cell lineages.


Once upon a dish: the next frontier in engineering multicellular systems
Meritxell Huch,Mina Gouti



Pancreas organoid models of development and regeneration
Anne Grapin-Botton,Yung Hae Kim
Summary: This Review summarises the methods that have been developed to generate pancreas organoids in vitro and discusses how they have been used to uncover aspects of pancreas development and their potential for future discoveries.

Stem cell-based models of early mammalian development
Aidan H. Terhune,Jeyoon Bok,Shiyu Sun,Jianping Fu
Summary: In this Review, we examine the various human and mouse stem-cell based models that recapitulate key features of early embryogenesis, and discuss their applications and findings.

Human stem cell models to study placode development, function and pathology
Eleonora Conti,Oliver Harschnitz
Summary: This Review describes how human pluripotent stem cells can be differentiated towards placode progenitors and their highly diverse derivatives providing a model system to study placode development, physiology and pathology in a human setting.


Mapping the adult human esophagus in vivo and in vitro
Daysha Ferrer-Torres,Joshua H. Wu,Charles J. Zhang,Max A. Hammer,Michael K. Dame,Angeline Wu,Emily M. Holloway,Kateryna Karpoff,Caroline L. McCarthy,Margaret S. Bohm,Ashley J. Cuttitta,Dominic J. Tigani,Sha Huang,Yu-Hwai Tsai,Alyssa J. Miller,Taylor Walker,David E. Bayer,Simon P. Hogan,Danielle Kim Turgeon,Jules Lin,Peter D. R. Higgins,Jonathan Sexton,Jason R. Spence
Summary: A detailed protocol for long-term culture of human esophagus tissue enabling benchmarking of in vitro models against a cell-type atlas of adult human esophagus and establishment of a diverse biobank of in vitro esophagus tissue.

Laminin 511 and WNT signalling sustain prolonged expansion of hiPSC-derived hippocampal progenitors
Keagan Dunville,Fabrizio Tonelli,Elena Novelli,Azzurra Codino,Verediana Massa,Anna Maria Frontino,Silvia Galfrè,Francesca Biondi,Stefano Gustincich,Matteo Caleo,Luca Pandolfini,Claudia Alia,Federico Cremisi
Summary: WNT signalling and laminin 511 support the in vitro expansion of hippocampal progenitor cells, opening new avenues for studying cell type-dependent neurogenesis, synaptic transmission in the hippocampus and future cell-based therapies.

PHLPP1 regulates CFTR activity and lumen expansion through AMPK
Viola H. Lobert,Maren L. Skardal,Lene Malerød,Julia E. Simensen,Hermine A. Algra,Aram N. Andersen,Thomas Fleischer,Hilde A. Enserink,Knut Liestøl,Joan K. Heath,Tor Erik Rusten,Harald A. Stenmark
Summary: A human 3D culture model reveals that pleckstrin homology leucine-rich repeat phosphatase 1 is a previously unidentified regulator of the cystic fibrosis transmembrane conductance regulator channel.

Imaging three-dimensional brain organoid architecture from meso- to nanoscale across development
Juan Eduardo Rodriguez-Gatica,Vira Iefremova,Liubov Sokhranyaeva,Si Wah Christina Au Yeung,Yannik Breitkreuz,Oliver Brüstle,Martin Karl Schwarz,Ulrich Kubitscheck
Summary: The combination of light-sheet fluorescence and expansion microscopy enables imaging of mature human brain organoids in toto and down to synaptic resolution.

Practical guide for preparation, computational reconstruction and analysis of 3D human neuronal networks in control and ischaemic conditions
Noora Räsänen,Venla Harju,Tiina Joki,Susanna Narkilahti
Summary: An optimized protocol is presented that allows morphological, quantifiable differences between the damaged and control human neuronal networks to be detected in three-dimensional cultures.

Human neural progenitors establish a diffusion barrier in the endoplasmic reticulum membrane during cell division
Muhammad Khadeesh bin Imtiaz,Lars N. Royall,Daniel Gonzalez-Bohorquez,Sebastian Jessberger
Summary: Asymmetric segregation of cellular components, which may contribute to the fate and behavior of human neural progenitors, is allowed by a diffusion barrier in the endoplasmic reticulum membrane during cell division.

Mechanisms underlying WNT-mediated priming of human embryonic stem cells
Anna Yoney,Lu Bai,Ali H. Brivanlou,Eric D. Siggia
Summary: The key developmental transcription factor eomesodermin can replace Wnt priming in the differentiation of human embryonic stem cells into mesendoderm.

Human iPSC-derived cerebral organoids model features of Leigh syndrome and reveal abnormal corticogenesis
Alejandra I. Romero-Morales,Gabriella L. Robertson,Anuj Rastogi,Megan L. Rasmussen,Hoor Temuri,Gregory Scott McElroy,Ram Prosad Chakrabarty,Lawrence Hsu,Paula M. Almonacid,Bryan A. Millis,Navdeep S. Chandel,Jean-Philippe Cartailler,Vivian Gama
Summary: Induced pluripotent stem cell-derived model systems reveal defects in early neurogenesis due to dysregulation of key metabolic pathways associated with Leigh syndrome.

Generation of functional human oligodendrocytes from dermal fibroblasts by direct lineage conversion
Koji Tanabe,Hiroko Nobuta,Nan Yang,Cheen Euong Ang,Philip Huie, Jr,Sacha Jordan,Michael C. Oldham,David H. Rowitch,Marius Wernig
Summary: This paper shows the generation of myelinating human oligodendrocytes from dermal fibroblasts using a direct lineage conversion technique, which could be of high interest for regenerative medicine applications.


Self-organizing in vitro mouse neural tube organoids mimic embryonic development
JiSoo Park,Hao-An Hsiung,Irina Khven,Gioele La Manno,Matthias P. Lutolf
Summary: Self-elongating neural tube organoids recapitulate key aspects of the morphology, anterior-posterior patterning, neural crest emergence and neural differentiation of mouse embryo in vivo by self-organization.

Hypoxia induces an early primitive streak signature, enhancing spontaneous elongation and lineage representation in gastruloids
Natalia López-Anguita,Seher Ipek Gassaloglu,Maximilian Stötzel,Adriano Bolondi,Deniz Conkar,Marina Typou,René Buschow,Jesse V. Veenvliet,Aydan Bulut-Karslioglu
Summary: Prolonged hypoxia (reduced oxygen tension) induces WNT pathway activity and is harnessed to enhance differentiation of embryonic stem cells into gastruloids.

Microgel culture and spatial identity mapping elucidate the signalling requirements for primate epiblast and amnion formation
Clara Munger,Timo N. Kohler,Erin Slatery,Anna L. Ellermann,Sophie Bergmann,Christopher A. Penfold,Ioakeim Ampartzidis,Yutong Chen,Florian Hollfelder,Thorsten E. Boroviak
Summary: A high-throughput microfluidic-based platform to decipher the essential cues for embryonic and extraembryonic lineage specification in primate embryogenesis.

Rapid and robust directed differentiation of mouse epiblast stem cells into definitive endoderm and forebrain organoids
Daniel Medina-Cano,Emily K. Corrigan,Rachel A. Glenn,Mohammed T. Islam,Yuan Lin,Juliet Kim,Hyunwoo Cho,Thomas Vierbuchen
Summary: New optimized protocols for directed differentiation of mouse epiblast stem cells into definitive endoderm and forebrain-patterned organoids.

Stable iPSC-derived NKX2-1+ lung bud tip progenitor organoids give rise to airway and alveolar cell types
Renee F. C. Hein,Ansley S. Conchola,Alexis S. Fine,Zhiwei Xiao,Tristan Frum,Lindy K. Brastrom,Mayowa A. Akinwale,Charlie J. Childs,Yu-Hwai Tsai,Emily M. Holloway,Sha Huang,John Mahoney,Idse Heemskerk,Jason R. Spence
Summary: iPSC-derived lung bud tip progenitors emerge in organoid culture, can be isolated and expanded, are transcriptionally similar to primary bud tip progenitors, and can differentiate into airway or alveolar organoids.

A pendulum of induction between the epiblast and extra-embryonic endoderm supports post-implantation progression
Erik J. Vrij,Yvonne S. Scholte op Reimer,Laury Roa Fuentes,Isabel Misteli Guerreiro,Viktoria Holzmann,Javier Frias Aldeguer,Giovanni Sestini,Bon-Kyoung Koo,Jop Kind,Clemens A. van Blitterswijk,Nicolas C. Rivron
Summary: A set of molecules directs the co-formation of blastocyst-stage primitive endoderm-like and epiblast-like cells in embryoid bodies and blastoids. This embryonic–extra-embryonic niche self-organizes and progresses through post-implantation-like stages via a sequence of mutual inductions.


A microfluidic platform to investigate the role of mechanical constraints on tissue reorganization
Sham L. Tlili,François Graner,Hélène Delanoë-Ayari
Summary: Aspiration of embryonic cell aggregates through microfluidic channels, in combination with two-photon imaging, reveals spatiotemporal deformations, visco-elastic properties and cell rearrangement dynamics that could play a role in developmental tissue organization.

Last Updated: 2022-12-01