Unravelling stem cell dynamics by lineage tracing

2013 ◽  
Vol 14 (8) ◽  
pp. 489-502 ◽  
Author(s):  
Cédric Blanpain ◽  
Benjamin D. Simons
Keyword(s):  
Stem Cell ◽  
Lineage Tracing ◽  
Cell Dynamics

scholarly journals Stem cell dynamics in mouse hair follicles: A story from cell division counting and single cell lineage tracing

Cell Cycle ◽  
2010 ◽  
Vol 9 (8) ◽  
pp. 1504-1510 ◽  
Author(s):  
Ying V. Zhang ◽  
Brian S. White ◽  
David I. Shalloway ◽  
Tudorita Tumbar
Keyword(s):  
Stem Cell ◽  
Cell Division ◽  
Single Cell ◽  
Cell Lineage ◽  
Hair Follicles ◽  
Lineage Tracing ◽  
Cell Dynamics

scholarly journals Mature enteroendocrine cells contribute to basal and pathological stem cell dynamics in the small intestine

2018 ◽  
Vol 315 (4) ◽  
pp. G495-G510 ◽  
Author(s):  
Yoshitatsu Sei ◽  
Jianying Feng ◽  
Leigh Samsel ◽  
Ayla White ◽  
Xilin Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Intestinal Epithelium ◽  
Lineage Tracing ◽  
Enteroendocrine Cells ◽  
Intestinal Stem Cells ◽  
Intestinal Tumors ◽  
Cell Dynamics ◽  
Neutral Drift ◽  
Rapid Generation

Lgr5-expressing intestinal stem cells (ISCs) maintain continuous and rapid generation of the intestinal epithelium. Here, we present evidence that dedifferentiation of committed enteroendocrine cells (EECs) contributes to maintenance of the epithelium under both basal conditions and in response to injury. Lineage-tracing studies identified a subset of EECs that reside at +4 position for more than 2 wk, most of which were BrdU-label-retaining cells. Under basal conditions, cells derived from these EECs grow from the bottom of the crypt to generate intestinal epithelium according to neutral drift kinetics that is consistent with dedifferentiation of mature EECs to ISCs. The lineage tracing of EECs demonstrated reserve stem cell properties in response to radiation-induced injury with the generation of reparative EEC-derived epithelial patches. Finally, the enterochromaffin (EC) cell was the predominant EEC type participating in these stem cell dynamics. These results provide novel insights into the +4 reserve ISC hypothesis, stem cell dynamics of the intestinal epithelium, and in the development of EC-derived small intestinal tumors. NEW & NOTEWORTHY The current manuscript demonstrating that a subset of mature enteroendocrine cells (EECs), predominantly enterochromaffin cells, dedifferentiates to fully functional intestinal stem cells (ISCs) is novel, timely, and important. These cells dedifferentiate to ISCs not only in response to injury but also under basal homeostatic conditions. These novel findings provide a mechanism in which a specified cell can dedifferentiate and contribute to normal tissue plasticity as well as the development of EEC-derived intestinal tumors under pathologic conditions.

scholarly journals aPKCλ controls epidermal homeostasis and stem cell fate through regulation of division orientation

2013 ◽  
Vol 202 (6) ◽  
pp. 887-900 ◽  
Author(s):  
Michaela T. Niessen ◽  
Jeanie Scott ◽  
Julia G. Zielinski ◽  
Susanne Vorhagen ◽  
Panagiota A. Sotiropoulou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Lineage Tracing ◽  
Premature Aging ◽  
Temporary Increase ◽  
Proliferative Potential ◽  
Cell Dynamics ◽  
Asymmetric Divisions

The atypical protein kinase C (aPKC) is a key regulator of polarity and cell fate in lower organisms. However, whether mammalian aPKCs control stem cells and fate in vivo is not known. Here we show that loss of aPKCλ in a self-renewing epithelium, the epidermis, disturbed tissue homeostasis, differentiation, and stem cell dynamics, causing progressive changes in this tissue. This was accompanied by a gradual loss of quiescent hair follicle bulge stem cells and a temporary increase in proliferating progenitors. Lineage tracing analysis showed that loss of aPKCλ altered the fate of lower bulge/hair germ stem cells. This ultimately led to loss of proliferative potential, stem cell exhaustion, alopecia, and premature aging. Inactivation of aPKCλ produced more asymmetric divisions in different compartments, including the bulge. Thus, aPKCλ is crucial for homeostasis of self-renewing stratifying epithelia, and for the regulation of cell fate, differentiation, and maintenance of epidermal bulge stem cells likely through its role in balancing symmetric and asymmetric division.

scholarly journals Fluctuating methylation clocks for cell lineage tracing at high temporal resolution in human tissues

2022 ◽  
Author(s):  
Calum Gabbutt ◽  
Ryan O. Schenck ◽  
Daniel J. Weisenberger ◽  
Christopher Kimberley ◽  
Alison Berner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lineage ◽  
Adult Stem Cell ◽  
Lineage Tracing ◽  
Rapid Expansion ◽  
High Temporal Resolution ◽  
Molecular Clocks ◽  
Cell Renewal ◽  
Cell Dynamics ◽  
Small Intestinal

AbstractMolecular clocks that record cell ancestry mutate too slowly to measure the short-timescale dynamics of cell renewal in adult tissues. Here, we show that fluctuating DNA methylation marks can be used as clocks in cells where ongoing methylation and demethylation cause repeated ‘flip–flops’ between methylated and unmethylated states. We identify endogenous fluctuating CpG (fCpG) sites using standard methylation arrays and develop a mathematical model to quantitatively measure human adult stem cell dynamics from these data. Small intestinal crypts were inferred to contain slightly more stem cells than the colon, with slower stem cell replacement in the small intestine. Germline APC mutation increased the number of replacements per crypt. In blood, we measured rapid expansion of acute leukemia and slower growth of chronic disease. Thus, the patterns of human somatic cell birth and death are measurable with fluctuating methylation clocks (FMCs).

Abstract P011: Endothelial Differentiation and Lineage Tracing in Adipocyte-Derived Multipotent Cells

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Medet Jumabay ◽  
Raushan Abdmaulen ◽  
Yucheng Yao ◽  
Kristina Bostrom
Keyword(s):  
Stem Cell ◽  
Lineage Tracing ◽  
Collagen Gels ◽  
Cellular Origin ◽  
Differentiated Cells ◽  
Stem Cell Source ◽  
Cardiovascular Regeneration ◽  
Morphogenetic Protein ◽  
Dfat Cells

We previously showed that so-called de-differentiated fat (DFAT) cells, which are derived from mature white adipocytes, spontaneously differentiate into beating cardiomyocytes. Our aim in this study was to investigate if DFAT cells also differentiate into endothelial cells (ECs) in vitro, and to further examine the cellular origin of DFAT cells as well as adipose stromal cells (ASCs) using lineage tracing. First, we examined DFAT and ASCs prepared from aP2-Cre+/+;LacZ ROSA(R26R)+/+ double transgenic mice, which express LacZ under the aP2 promoter. The results revealed that 99.9% of DFAT cells and 45% of the ASCs stained positive for LacZ, supporting that the DFAT cells and part of the ASCs are of adipocytic origin. Second, we allowed newly isolated DFAT cells to spontaneously undergo EC differentiation, which was monitored by expression of EC lineage markers as determined by real-time PCR, immunofluorescence, and FACS. Expression of the EC markers CD31 and VE-cadherin increased progressively during 2 weeks in culture, the percentage of CD31(+) cells increased from 0.0% to 8.3%, and the cells formed multi-cellular tube structures when placed in Matrigel™/Collagen gels. The data supported that a fraction of the DFAT cells differentiate into ECs. Furthermore, the EC differentiation could be enhanced in DFAT cells by treatment with bone morphogenetic protein (BMP)-4 and BMP-9. In addition to EC differentiation, the DFAT cells also expressed markers of other cardiovascular lineages including smooth muscle cells and pericytes. The multipotency of DFAT cells suggests that cellular de-differentiation might be a way for differentiated cells to regain stem cell-like properties. Thus, white mature adipocytes maybe a new stem cell source for cardiovascular regeneration.

scholarly journals Tales from the crypt: intestinal niche signals in tissue renewal, plasticity and cancer

Open Biology ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. 180120 ◽  
Author(s):  
Maureen Spit ◽  
Bon-Kyoung Koo ◽  
Madelon M. Maurice
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Signalling Pathways ◽  
Intestinal Homeostasis ◽  
Cell Dynamics ◽  
Cell Proliferation And Differentiation ◽  
Colorectal Cancer Cells ◽  
Recent Developments ◽  
Mutational Activation ◽  
Stem Cell Populations

Rapidly renewing tissues such as the intestinal epithelium critically depend on the activity of small-sized stem cell populations that continuously generate new progeny to replace lost and damaged cells. The complex and tightly regulated process of intestinal homeostasis is governed by a variety of signalling pathways that balance cell proliferation and differentiation. Accumulating evidence suggests that stem cell control and daughter cell fate determination is largely dictated by the microenvironment. Here, we review recent developments in the understanding of intestinal stem cell dynamics, focusing on the roles, mechanisms and interconnectivity of prime signalling pathways that regulate stem cell behaviour in intestinal homeostasis. Furthermore, we discuss how mutational activation of these signalling pathways endows colorectal cancer cells with niche-independent growth advantages during carcinogenesis.

scholarly journals Stem cell dynamics and pretumor progression in the intestinal tract

2016 ◽  
Vol 51 (9) ◽  
pp. 841-852 ◽  
Author(s):  
Huiying Ma ◽  
Folkert H. M. Morsink ◽  
George Johan Arnold Offerhaus ◽  
Wendy W. J. de Leng
Keyword(s):  
Stem Cell ◽  
Intestinal Tract ◽  
Cell Dynamics
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