scholarly journals From head to tail: regionalization of the neural crest

Development ◽  
2020 ◽  
Vol 147 (20) ◽  
pp. dev193888
Author(s):  
Manuel Rocha ◽  
Anastasia Beiriger ◽  
Elaine E. Kushkowski ◽  
Tetsuto Miyashita ◽  
Noor Singh ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Neural Crest ◽  
Neural Crest Cells ◽  
Stem Cell Differentiation ◽  
Lineage Tracing ◽  
Current Understanding ◽  
Genetic Circuits ◽  
Developmental Potential ◽  
Experimental Embryology

ABSTRACTThe neural crest is regionalized along the anteroposterior axis, as demonstrated by foundational lineage-tracing experiments that showed the restricted developmental potential of neural crest cells originating in the head. Here, we explore how recent studies of experimental embryology, genetic circuits and stem cell differentiation have shaped our understanding of the mechanisms that establish axial-specific populations of neural crest cells. Additionally, we evaluate how comparative, anatomical and genomic approaches have informed our current understanding of the evolution of the neural crest and its contribution to the vertebrate body.

scholarly journals Clonal inactivation of telomerase promotes accelerated stem cell differentiation

2021 ◽  
Author(s):  
Kazuteru Hasegawa ◽  
Yang Zhao ◽  
Alina Garbuzov ◽  
M. Ryan Corces ◽  
Lu Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Cell Function ◽  
Stem Cell Differentiation ◽  
Lineage Tracing ◽  
Open Chromatin ◽  
Loss Of Function ◽  
Direct Role ◽  
A Genome

SummaryTelomerase is intimately associated with stem cells and upregulated in cancer, where it serves essential roles through its catalytic action in elongating telomeres, nucleoprotein caps that protect chromosome ends1. Overexpression of the telomerase reverse transcriptase (TERT) enhances cell proliferation through telomere-independent means, yet definitive evidence for such a direct role in stem cell function has yet to be revealed through loss-of-function studies. Here, we show that conditional deletion of TERT in spermatogonial stem cells (SSCs) markedly impairs competitive clone formation. Using lineage-tracing from the Tert locus, we find that TERT-expressing SSCs yield long-lived clones, but that selective TERT-inactivation in SSCs causes accelerated stem cell differentiation thereby disrupting clone formation. This requirement for TERT in clone formation is bypassed by expression of a catalytically inactive TERT transgene and occurs independently of the canonical telomerase complex. TERT inactivation induces a genome-wide reduction in open chromatin evident in purified SSCs, but not in committed progenitor cells. Loss of TERT causes reduced activity of the MYC oncogene and transgenic expression of MYC in TERT-deleted SSCs efficiently rescues clone formation. These data reveal a required catalytic activity-independent role for TERT in preventing stem cell differentiation, forge a genetic link between TERT and MYC and suggest new means by which TERT may promote tumorigenesis.

scholarly journals Regulation of Boundary Cap Neural Crest Stem Cell Differentiation After Transplantation

Stem Cells ◽  
2009 ◽  
Vol 27 (7) ◽  
pp. 1592-1603 ◽  
Author(s):  
Hakan Aldskogius ◽  
Christian Berens ◽  
Nadezda Kanaykina ◽  
Anna Liakhovitskaia ◽  
Alexander Medvinsky ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Neural Crest ◽  
Stem Cell Differentiation ◽  
Neural Crest Stem Cell

scholarly journals Persistence of a novel regeneration-associated transitional cell state in pulmonary fibrosis

2019 ◽  
Author(s):  
Yoshihiko Kobayashi ◽  
Aleksandra Tata ◽  
Arvind Konkimalla ◽  
Hiroaki Katsura ◽  
Rebecca F. Lee ◽  
...  
Keyword(s):  
Dna Damage ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Pulmonary Fibrosis ◽  
Stem Cell Differentiation ◽  
Lineage Tracing ◽  
Cell Senescence ◽  
Alveolar Type ◽  
Transitional State

AbstractStem cell senescence is often seen as an age associated pathological state in which cells acquire an abnormal and irreversible state. Here, we show that alveolar stem cell differentiation during lung regeneration involves a unique previously uncharacterized transitional state that exhibits cardinal features normally associated with cell senescence. Specifically, using organoid cultures, multiple in vivo injury models coupled with single cell transcriptomics and lineage tracing analysis, we find that alveolar stem cell differentiation involves a novel, pre-alveolar type-1 transitional state (PATS) en route to their terminal maturation. PATS can be distinguished based on their unique transcriptional signatures, including enrichment for TP53, TGFβ, and DNA damage repair signaling, and cellular senescence in both in vivo and ex vivo regenerating tissues. Significantly, PATS undergo extensive cell stretching, which makes them vulnerable to DNA damage, a feature commonly associated with most degenerative lung diseases. Importantly, we find enrichment of PATS-like state in human fibrotic lung tissues, suggesting that persistence of such transitional states underlies the pathogenesis of pulmonary fibrosis. Our study thus redefines senescence as a state that can occur as part of a normal tissue maintenance program, and can be derailed in human disease, notably fibrosis.

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