scholarly journals Faster, higher, stronger: timely and robust cell fate/identity commitment in stem cell lineages

Open Biology ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 180243 ◽  
Author(s):  
Kun Liu ◽  
Ke Xu ◽  
Yan Song
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Transcriptional Control ◽  
Cell Lineage ◽  
Cell Fate Specification ◽  
Developmental Abnormalities ◽  
Cell Lineages ◽  
Identity Commitment ◽  
Regulatory Strategies ◽  
Stem Cell Lineage

Precise specification of cell fate or identity within stem cell lineages is critical for ensuring correct stem cell lineage progression and tissue homeostasis. Failure to specify cell fate or identity in a timely and robust manner can result in developmental abnormalities and diseases such as cancer. However, the molecular basis of timely cell fate/identity specification is only beginning to be understood. In this review, we discuss key regulatory strategies employed in cell fate specification and highlight recent results revealing how timely and robust cell fate/identity commitment is achieved through transcriptional control.

scholarly journals Intracellular pH dynamics regulates intestinal stem cell fate

2021 ◽  
Author(s):  
Diane L. Barber ◽  
Yi Liu ◽  
Efren Reyes ◽  
David Castillo-Azofeifa ◽  
Ophir D Klein ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Intracellular Ph ◽  
Paneth Cell ◽  
Cell Lineage ◽  
Adult Stem Cell ◽  
Intestinal Stem Cell ◽  
Cell Fate Specification ◽  
Stem Cell Fate ◽  
Stem Cell Lineage

Emerging evidence is revealing critical roles of intracellular pH (pHi) in development, but it remains unclear whether pHi regulates stem cell fate specification. We find that pHi dynamics is a key regulator of cell fate in the mouse intestinal stem cell lineage. We identify a pHi gradient along the intestinal crypt axis and find that dissipating this gradient inhibits crypt budding due to loss Paneth cell differentiation. Mechanistically, decreasing pHi biases intestinal stem cell fate toward the absorptive and away from the secretory lineage, by regulating the activity of the lineage transcription factor Atoh1. Our findings reveal a previously unrecognized role for pHi dynamics in the specification of cell fate within an adult stem cell lineage.

scholarly journals Biomimetic three-dimensional microenvironment for controlling stem cell fate

2011 ◽  
Vol 1 (5) ◽  
pp. 792-803 ◽  
Author(s):  
Hu Zhang ◽  
Sheng Dai ◽  
Jingxiu Bi ◽  
Kuo-Kang Liu
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Three Dimensional ◽  
Cell Lineage ◽  
Cell Interaction ◽  
Stem Cell Fate ◽  
Cell Microenvironment ◽  
Stem Cell Lineage ◽  
Matrix Cell ◽  
The Individual

Stem cell therapy is an emerging technique which is being translated into treatment of degenerated tissues. However, the success of translation relies on the stem cell lineage commitment in the degenerated regions of interest. This commitment is precisely controlled by the stem cell microenvironment. Engineering a biomimetic three-dimensional microenvironment enables a thorough understanding of the mechanisms of governing stem cell fate. We review the individual microenvironment components, including soluble factors, extracellular matrix, cell–cell interaction and mechanical stimulation. The perspectives in creating the biomimetic microenvironments are discussed with emerging techniques.

scholarly journals Bi-directional cell-pericellular matrix interactions direct stem cell fate

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Silvia A. Ferreira ◽  
Meghna S. Motwani ◽  
Peter A. Faull ◽  
Alexis J. Seymour ◽  
Tracy T. L. Yu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Cell Lineage ◽  
Local Environment ◽  
Pericellular Matrix ◽  
Lineage Specification ◽  
Reciprocal Interactions ◽  
Stem Cell Lineage ◽  
Matrix Interactions ◽  
Insight Into

Abstract Modifiable hydrogels have revealed tremendous insight into how physical characteristics of cells’ 3D environment drive stem cell lineage specification. However, in native tissues, cells do not passively receive signals from their niche. Instead they actively probe and modify their pericellular space to suit their needs, yet the dynamics of cells’ reciprocal interactions with their pericellular environment when encapsulated within hydrogels remains relatively unexplored. Here, we show that human bone marrow stromal cells (hMSC) encapsulated within hyaluronic acid-based hydrogels modify their surroundings by synthesizing, secreting and arranging proteins pericellularly or by degrading the hydrogel. hMSC’s interactions with this local environment have a role in regulating hMSC fate, with a secreted proteinaceous pericellular matrix associated with adipogenesis, and degradation with osteogenesis. Our observations suggest that hMSC participate in a bi-directional interplay between the properties of their 3D milieu and their own secreted pericellular matrix, and that this combination of interactions drives fate.

bag-of-marbles and benign gonial cell neoplasm act in the germline to restrict proliferation during Drosophila spermatogenesis

Development ◽  
1997 ◽  
Vol 124 (21) ◽  
pp. 4361-4371 ◽  
Author(s):  
P. Gonczy ◽  
E. Matunis ◽  
S. DiNardo
Keyword(s):  
Stem Cell ◽  
Germ Cells ◽  
Daughter Cell ◽  
Cell Lineage ◽  
Germline Stem Cell ◽  
Cell Lineages ◽  
Male Germline ◽  
Stem Cell Lineage ◽  
Cell Neoplasm ◽  
Bag Of Marbles

Stem cells divide asymmetrically, regenerating a parental stem cell and giving rise to a daughter cell with a distinct fate. In many stem cell lineages, this daughter cell undergoes several amplificatory mitoses, thus generating more cells that embark on the differentiation program specific for the given lineage. Spermatogenesis in Drosophila is a model system to identify molecules regulating stem cell lineages. Mutations at two previously identified loci, bag-of-marbles (bam) and benign gonial cell neoplasm (bgcn), prevent progression through spermatogenesis and oogenesis, resulting in the overproliferation of undifferentiated germ cells. Here we investigate how bam and bgcn regulate the male germline stem cell lineage. By generating FLP-mediated clones, we demonstrate that both bam and bgcn act autonomously in the germline to restrict proliferation during spermatogenesis. By using enhancer trap lines, we find that the overproliferating germ cells express markers specific to amplifying germ cells, while at the same time retaining the expression of some markers of stem cell and primary spermatogonial cell fate. However, we find that germ cells accumulating in bam or bgcn mutant testes most resemble amplifying germ cells, because they undergo incomplete cytokinesis and progress through the cell cycle in synchrony within a cyst, which are two characteristics of amplifying germ cells, but not of stem cells. Taken together, our results suggest that bam and bgcn regulate progression through the male germline stem cell lineage by cell-intrinsically restricting the proliferation of amplifying germ cells.

Lox2, a putative leech segment identity gene, is expressed in the same segmental domain in different stem cell lineages

Development ◽  
1992 ◽  
Vol 116 (3) ◽  
pp. 697-710 ◽  
Author(s):  
D. Nardelli-Haefliger ◽  
M. Shankland
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Gene Products ◽  
Cell Lineages ◽  
Stem Cell Lineage ◽  
Hybridization Reaction ◽  
Cell Segment

The segmented tissues of the adult leech arise from a set of five, bilaterally paired embryonic stem cells via a stereotyped sequence of cell lineage. Individual segments exhibit unique patterns of cell differentiation, and previous studies have suggested that each stem cell lineage establishes at least some aspects of its own segmental specificity autonomously. In this paper, we describe a putative leech segment identity gene, Lox2, and examine its expression in the various stem cell lineages. Both sequence analysis and the segmental pattern of Lox2 expression suggest a specific homology to the fruitfly segment identity genes Ubx and abdA. In situ hybridization reveals a cellular accumulation of Lox2 RNA over a contiguous domain of 16 midbody segments (M6-M21), including postmitotic neurons, muscles and the differentiating genitalia. Lox2 transcripts were not detected at the stage when segment identities are first established, suggesting that Lox2 gene products may not be part of the initial specification process. Individual stem cell lineages were labeled by intracellular injection of fluorescent tracers, and single cell colocalization of lineage tracer and hybridization reaction product revealed expression of Lox2 RNA in the progeny of four different stem cells. The segmental domain of Lox2 RNA was very similar in the various stem cell lineages, despite the fact that some stem cells generate one founder cell/segment, whereas other stem cells generate two founder cells/segment.

scholarly journals Telomere dysfunction cooperates with epigenetic alterations to impair murine embryonic stem cell fate commitment

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Mélanie Criqui ◽  
Aditi Qamra ◽  
Tsz Wai Chu ◽  
Monika Sharma ◽  
Julissa Tsao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Chromatin Accessibility ◽  
Telomere Dysfunction ◽  
Epigenetic Alterations ◽  
Dna Hypomethylation ◽  
Murine Embryonic Stem Cell ◽  
Stem Cell Lineage

The precise relationship between epigenetic alterations and telomere dysfunction is still an extant question. Previously, we showed that eroded telomeres lead to differentiation instability in murine embryonic stem cells (mESCs) via DNA hypomethylation at pluripotency-factor promoters. Here, we uncovered that telomerase reverse transcriptase null (Tert-/-) mESCs exhibit genome-wide alterations in chromatin accessibility and gene expression during differentiation. These changes were accompanied by an increase of H3K27me3 globally, an altered chromatin landscape at the Pou5f1/Oct4 promoter, and a refractory response to differentiation cues. Inhibition of the Polycomb Repressive Complex 2 (PRC2), an H3K27 tri-methyltransferase, exacerbated the impairment in differentiation and pluripotency gene repression in Tert-/- mESCs but not wild-type mESCs, whereas inhibition of H3K27me3 demethylation led to a partial rescue of the Tert-/- phenotype. These data reveal a new interdependent relationship between H3K27me3 and telomere integrity in stem cell lineage commitment that may have implications in aging and cancer.

scholarly journals A mex3 homolog is required for differentiation during planarian stem cell lineage development

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Shu Jun Zhu ◽  
Stephanie E Hallows ◽  
Ko W Currie ◽  
ChangJiang Xu ◽  
Bret J Pearson
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Adult Stem Cells ◽  
Rna Binding ◽  
Transcriptional Profiling ◽  
Cell Lineage ◽  
Functional Screening ◽  
Differentiated Cells ◽  
Stem Cell Lineage ◽  
A Cell

Neoblasts are adult stem cells (ASCs) in planarians that sustain cell replacement during homeostasis and regeneration of any missing tissue. While numerous studies have examined genes underlying neoblast pluripotency, molecular pathways driving postmitotic fates remain poorly defined. In this study, we used transcriptional profiling of irradiation-sensitive and irradiation-insensitive cell populations and RNA interference (RNAi) functional screening to uncover markers and regulators of postmitotic progeny. We identified 32 new markers distinguishing two main epithelial progenitor populations and a planarian homolog to the MEX3 RNA-binding protein (Smed-mex3-1) as a key regulator of lineage progression. mex3-1 was required for generating differentiated cells of multiple lineages, while restricting the size of the stem cell compartment. We also demonstrated the utility of using mex3-1(RNAi) animals to identify additional progenitor markers. These results identified mex3-1 as a cell fate regulator, broadly required for differentiation, and suggest that mex3-1 helps to mediate the balance between ASC self-renewal and commitment.

Using Single-Cell and Spatial Transcriptomes to Understand Stem Cell Lineage Specification During Early Embryo Development

2020 ◽  
Vol 21 (1) ◽  
pp. 163-181
Author(s):  
Guangdun Peng ◽  
Guizhong Cui ◽  
Jincan Ke ◽  
Naihe Jing
Keyword(s):  
Stem Cell ◽  
Single Cell ◽  
Rna Sequencing ◽  
Cell Fate ◽  
Cell Lineage ◽  
Stem Cell Differentiation ◽  
Early Embryo ◽  
Stem Cell Lineage ◽  
Single Cell Rna Sequencing ◽  
Cell Organization

Embryonic development and stem cell differentiation provide a paradigm to understand the molecular regulation of coordinated cell fate determination and the architecture of tissue patterning. Emerging technologies such as single-cell RNA sequencing and spatial transcriptomics are opening new avenues to dissect cell organization, the divergence of morphological and molecular properties, and lineage allocation. Rapid advances in experimental and computational tools have enabled researchers to make many discoveries and revisit old hypotheses. In this review, we describe the use of single-cell RNA sequencing in studies of molecular trajectories and gene regulation networks for stem cell lineages, while highlighting the integratedexperimental and computational analysis of single-cell and spatial transcriptomes in the molecular annotation of tissue lineages and development during postimplantation gastrulation.

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