The multiple facets of Cajal-Retzius neurons

ABSTRACT Cajal-Retzius neurons (CRs) are among the first-born neurons in the developing cortex of reptiles, birds and mammals, including humans. The peculiarity of CRs lies in the fact they are initially embedded into the immature neuronal network before being almost completely eliminated by cell death at the end of cortical development. CRs are best known for controlling the migration of glutamatergic neurons and the formation of cortical layers through the secretion of the glycoprotein reelin. However, they have been shown to play numerous additional key roles at many steps of cortical development, spanning from patterning and sizing functional areas to synaptogenesis. The use of genetic lineage tracing has allowed the discovery of their multiple ontogenetic origins, migratory routes, expression of molecular markers and death dynamics. Nowadays, single-cell technologies enable us to appreciate the molecular heterogeneity of CRs with an unprecedented resolution. In this Review, we discuss the morphological, electrophysiological, molecular and genetic criteria allowing the identification of CRs. We further expose the various sources, migration trajectories, developmental functions and death dynamics of CRs. Finally, we demonstrate how the analysis of public transcriptomic datasets allows extraction of the molecular signature of CRs throughout their transient life and consider their heterogeneity within and across species.

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Troy+ brain stem cells cycle through quiescence and regulate their number by sensing niche occupancy

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1715911114 ◽

2018 ◽

Vol 115 (4) ◽

pp. E610-E619 ◽

Cited By ~ 56

Author(s):

Onur Basak ◽

Teresa G. Krieger ◽

Mauro J. Muraro ◽

Kay Wiebrands ◽

Daniel E. Stange ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Number ◽

Lineage Tracing ◽

Rapid Expansion ◽

Molecular Signature ◽

Genetic Lineage ◽

Proliferating Cells ◽

Self Renewal ◽

Genetic Lineage Tracing

The adult mouse subependymal zone provides a niche for mammalian neural stem cells (NSCs). However, the molecular signature, self-renewal potential, and fate behavior of NSCs remain poorly defined. Here we propose a model in which the fate of active NSCs is coupled to the total number of neighboring NSCs in a shared niche. Using knock-in reporter alleles and single-cell RNA sequencing, we show that the Wnt target Tnfrsf19/Troy identifies both active and quiescent NSCs. Quantitative analysis of genetic lineage tracing of individual NSCs under homeostasis or in response to injury reveals rapid expansion of stem-cell number before some return to quiescence. This behavior is best explained by stochastic fate decisions, where stem-cell number within a shared niche fluctuates over time. Fate mapping proliferating cells using a Ki67iresCreER allele confirms that active NSCs reversibly return to quiescence, achieving long-term self-renewal. Our findings suggest a niche-based mechanism for the regulation of NSC fate and number.

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Ventricular, atrial and outflow tract heart progenitors arise from spatially and molecularly distinct regions of the primitive streak

10.1101/2020.07.12.198994 ◽

2020 ◽

Author(s):

Kenzo Ivanovitch ◽

Pablo Soro-Barrio ◽

Probir Chakravarty ◽

Rebecca A Jones ◽

S. Neda Mousavy Gharavy ◽

...

Keyword(s):

Single Cell ◽

Heart Development ◽

Primitive Streak ◽

Outflow Tract ◽

Lineage Tracing ◽

Molecular Signature ◽

Genetic Lineage ◽

Cardiac Progenitors ◽

Heart Field ◽

Genetic Lineage Tracing

AbstractThe heart develops from two sources of mesoderm progenitors, the first and second heart field (FHF and SHF). Using a single cell transcriptomic assay in combination with genetic lineage tracing, we find the FHF and SHF are subdivided into distinct pools of progenitors in gastrulating mouse embryos at earlier stages than previously thought. Each subpopulation has a distinct origin in the primitive streak. The first progenitors to leave the primitive streak contribute to the left ventricle, shortly after right ventricle progenitor emigrate, followed by the outflow tract and atrial progenitors. Although cells allocated to the outflow tract and atrium leave the primitive streak at a similar stage, they arise from different regions. Outflow tract originate from distal locations in the primitive streak while atrial progenitors are positioned more proximally. Moreover, single cell RNA sequencing demonstrates that the primitive streak cells contributing to the ventricles have a distinct molecular signature from those forming the outflow tract and atrium. We conclude that cardiac progenitors are pre-patterned within the primitive streak and this prefigures their allocation to distinct anatomical structures of the heart. Together, our data provide a new molecular and spatial map of mammalian cardiac progenitors that will support future studies of heart development, function and disease.

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Ventricular, atrial, and outflow tract heart progenitors arise from spatially and molecularly distinct regions of the primitive streak

PLoS Biology ◽

10.1371/journal.pbio.3001200 ◽

2021 ◽

Vol 19 (5) ◽

pp. e3001200

Author(s):

Kenzo Ivanovitch ◽

Pablo Soro-Barrio ◽

Probir Chakravarty ◽

Rebecca A. Jones ◽

Donald M. Bell ◽

...

Keyword(s):

Single Cell ◽

Heart Development ◽

Primitive Streak ◽

Outflow Tract ◽

Lineage Tracing ◽

Molecular Signature ◽

Genetic Lineage ◽

Cardiac Progenitors ◽

Heart Field ◽

Genetic Lineage Tracing

The heart develops from 2 sources of mesoderm progenitors, the first and second heart field (FHF and SHF). Using a single-cell transcriptomic assay combined with genetic lineage tracing and live imaging, we find the FHF and SHF are subdivided into distinct pools of progenitors in gastrulating mouse embryos at earlier stages than previously thought. Each subpopulation has a distinct origin in the primitive streak. The first progenitors to leave the primitive streak contribute to the left ventricle, shortly after right ventricle progenitor emigrate, followed by the outflow tract and atrial progenitors. Moreover, a subset of atrial progenitors are gradually incorporated in posterior locations of the FHF. Although cells allocated to the outflow tract and atrium leave the primitive streak at a similar stage, they arise from different regions. Outflow tract cells originate from distal locations in the primitive streak while atrial progenitors are positioned more proximally. Moreover, single-cell RNA sequencing demonstrates that the primitive streak cells contributing to the ventricles have a distinct molecular signature from those forming the outflow tract and atrium. We conclude that cardiac progenitors are prepatterned within the primitive streak and this prefigures their allocation to distinct anatomical structures of the heart. Together, our data provide a new molecular and spatial map of mammalian cardiac progenitors that will support future studies of heart development, function, and disease.

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SETD4-expressing cells contribute to pancreatic development and response to cerulein induced pancreatitis injury

Scientific Reports ◽

10.1038/s41598-021-92075-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jin-Ze Tian ◽

Sheng Xing ◽

Jing-Yi Feng ◽

Shu-Hua Yang ◽

Yan-Fu Ding ◽

...

Keyword(s):

Cell Population ◽

Acinar Cells ◽

Pancreatic Disease ◽

Lineage Tracing ◽

Genetic Lineage ◽

Pancreatic Development ◽

Histone Lysine Methyltransferase ◽

Population Potential ◽

Potential Applications ◽

Genetic Lineage Tracing

AbstractIn the adult pancreas, the presence of progenitor or stem cells and their potential involvement in homeostasis and regeneration remains unclear. Here, we identify that SET domain-containing protein 4 (SETD4), a histone lysine methyltransferase, is expressed in a small cell population in the adult mouse pancreas. Genetic lineage tracing shows that during pancreatic development, descendants of SETD4+ cells make up over 70% of pancreatic cells and then contribute to each pancreatic lineage during pancreatic homeostasis. SETD4+ cells generate newborn acinar cells in response to cerulein-induced pancreatitis in acinar compartments. Ablation of SETD4+ cells compromises regeneration of acinar cells, in contrast to controls. Our findings provide a new cellular narrative for pancreatic development, homeostasis and response to injury via a small SETD4+ cell population. Potential applications may act to preserve pancreatic function in case of pancreatic disease and/or damage.

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Genetic Lineage Tracing of Biliary Epithelial Cells

Methods in Molecular Biology - Hepatic Stem Cells ◽

10.1007/978-1-4939-8961-4_5 ◽

2018 ◽

pp. 45-57 ◽

Cited By ~ 2

Author(s):

Teresa Rubio-Tomás ◽

Beatriz Aguilar-Bravo ◽

Pau Sancho-Bru

Keyword(s):

Epithelial Cells ◽

Lineage Tracing ◽

Genetic Lineage ◽

Biliary Epithelial Cells ◽

Genetic Lineage Tracing

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Correction to: Genetic Lineage Tracing of Sca-1 + Cells Reveals Endothelial but Not Myogenic Contribution to the Murine Heart

Circulation ◽

10.1161/cir.0000000000000622 ◽

2018 ◽

Vol 138 (15) ◽

Keyword(s):

Lineage Tracing ◽

Genetic Lineage ◽

Genetic Lineage Tracing

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Hlf Expression Marks Early Emergence of Hematopoietic Stem Cell Precursors With Adult Repopulating Potential and Fate

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.728057 ◽

2021 ◽

Vol 9 ◽

Author(s):

Wanbo Tang ◽

Jian He ◽

Tao Huang ◽

Zhijie Bai ◽

Chaojie Wang ◽

...

Keyword(s):

Stem Cells ◽

Mouse Model ◽

Hematopoietic Stem Cells ◽

Fetal Liver ◽

Lineage Tracing ◽

Genetic Lineage ◽

Hematopoietic Stem ◽

Genetic Lineage Tracing

In the aorta-gonad-mesonephros (AGM) region of mouse embryos, pre-hematopoietic stem cells (pre-HSCs) are generated from rare and specialized hemogenic endothelial cells (HECs) via endothelial-to-hematopoietic transition, followed by maturation into bona fide hematopoietic stem cells (HSCs). As HECs also generate a lot of hematopoietic progenitors not fated to HSCs, powerful tools that are pre-HSC/HSC-specific become urgently critical. Here, using the gene knockin strategy, we firstly developed an Hlf-tdTomato reporter mouse model and detected Hlf-tdTomato expression exclusively in the hematopoietic cells including part of the immunophenotypic CD45– and CD45+ pre-HSCs in the embryonic day (E) 10.5 AGM region. By in vitro co-culture together with long-term transplantation assay stringent for HSC precursor identification, we further revealed that unlike the CD45– counterpart in which both Hlf-tdTomato-positive and negative sub-populations harbored HSC competence, the CD45+ E10.5 pre-HSCs existed exclusively in Hlf-tdTomato-positive cells. The result indicates that the cells should gain the expression of Hlf prior to or together with CD45 to give rise to functional HSCs. Furthermore, we constructed a novel Hlf-CreER mouse model and performed time-restricted genetic lineage tracing by a single dose induction at E9.5. We observed the labeling in E11.5 AGM precursors and their contribution to the immunophenotypic HSCs in fetal liver (FL). Importantly, these Hlf-labeled early cells contributed to and retained the size of the HSC pool in the bone marrow (BM), which continuously differentiated to maintain a balanced and long-term multi-lineage hematopoiesis in the adult. Therefore, we provided another valuable mouse model to specifically trace the fate of emerging HSCs during development.

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Unraveling the transcriptional networks that drive oligodendrocyte fate specification in Sonic hedgehog-responsive neocortical progenitors

10.1101/2020.10.18.344515 ◽

2020 ◽

Author(s):

Caitlin C. Winkler ◽

Luuli N. Tran ◽

Ellyn P. Milan ◽

Fernando García-Moreno ◽

Santos J. Franco

Keyword(s):

Sonic Hedgehog ◽

Wild Type Mouse ◽

Lineage Tracing ◽

Human Embryos ◽

Transcriptional Networks ◽

Genetic Lineage ◽

Gene Regulatory ◽

Oligodendrocyte Precursor ◽

Genetic Lineage Tracing ◽

Developing Nervous System

In the developing nervous system, progenitors first generate neurons before making astrocytes and oligodendrocytes. We previously showed that increased Sonic hedgehog (Shh) signaling in dorsal forebrain progenitors is important for their production of oligodendrocytes as neurogenesis winds down. Here, we analyzed single-cell RNA sequencing datasets to better understand how Shh controls this neuron-to-oligodendrocyte switch in the neocortex. We first identified Shh-responding progenitors using a dataset in which Shh was overexpressed in the mouse dorsal forebrain. Pseudotime trajectory inferences revealed a subpopulation committed to the oligodendrocyte precursor cell (OPC) lineage. Genes upregulated along this lineage defined a pre-OPC state, as cells transitioned from progenitors to OPCs. Using several datasets from wild-type mouse and human embryos at different ages, we confirmed a pre-OPC state preceding OPC emergence during normal development. Finally, we show that pre-OPCs are enriched for a gene regulatory network involving the transcription factor Ascl1. Genetic lineage-tracing demonstrated Ascl1+ dorsal progenitors primarily make oligodendrocytes. We propose a model in which Shh shifts the balance between opposing transcriptional networks toward an Ascl1 lineage, thereby facilitating the switch between neurogenesis and oligodendrogenesis.

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