Single-cell gene expression analysis reveals diversity among human spermatogonia DOI Open Access
Nina Neuhaus, Juyong Yoon,

Nicole Terwort

et al.

Molecular Human Reproduction, Journal Year: 2017, Volume and Issue: unknown

Published: Jan. 15, 2017

Is the molecular profile of human spermatogonia homogeneous or heterogeneous when analysed at single-cell level? Heterogeneous expression profiles may be a key characteristic spermatogonia, supporting existence stem cell population. Despite fact that many studies have sought to identify specific markers for fingerprint these cells remains hitherto unknown. Testicular tissues from patients with spermatogonial arrest (arrest, n = 1) and qualitatively normal spermatogenesis (normal, 7) were selected pool 179 consecutively obtained biopsies. Gene analyses populations single-cells (n 105) performed. Two OCT4-positive individual global transcriptional capture using shallow RNA-seq. Finally, four candidate was assessed by immunohistochemistry. Histological analysis blood hormone measurements LH, FSH testosterone performed prior testicular sample selection. Following enzymatic digestion tissues, differential plating subsequent micromanipulation employed enrich isolate respectively. Endpoint qPCR cells, RNA-seq immunohistochemical analyses. Unexpectedly, data patient (20 cells) showed profiles. Also, spermatogenesis, patterns undifferentiated (OCT4, UTF1 MAGE A4) differentiated marker genes (BOLL PRM2) within each cluster (13 clusters 85 cells). Shallow validated, spermatogonia-specific protein (DDX5, TSPY1, EEF1A1 NGN3) demonstrated. The heterogeneity RNA levels is snapshot. To further assess functional meaning this dynamics populations, approaches need developed facilitate repeated cells. Our suggest model Future will in fertile infertile patients. published GEO database: GSE91063. This work supported Max Planck Society Deutsche Forschungsgemeinschaft DFG-Research Unit FOR 1041 Germ Cell Potential (grant numbers SCHO 340/7-1, SCHL394/11–2). authors declare there no conflict interest.

Language: Английский

Context-aware synthetic biology by controller design: Engineering the mammalian cell DOI Creative Commons
Nika Shakiba, Ross D. Jones,

Ron Weiss

et al.

Cell Systems, Journal Year: 2021, Volume and Issue: 12(6), P. 561 - 592

Published: June 1, 2021

Language: Английский

Citations

59
Skeletal stem and progenitor cells in bone development and repair DOI Creative Commons
Dana Trompet, Seppe Melis, Andrei S. Chagin

et al.

Journal of Bone and Mineral Research, Journal Year: 2024, Volume and Issue: unknown

Published: April 30, 2024

Abstract Bone development, growth, and repair are complex processes involving various cell types interactions, with central roles played by skeletal stem progenitor cells. Recent research brought new insights into the precursor populations that mediate intramembranous endochondral bone development. Later in life, many of cellular molecular mechanisms determining development reactivated upon fracture, powerful trauma-induced signaling cues triggering a variety postnatal stem/progenitor cells (SSPCs) residing near defect. Interestingly, this injury context, current evidence suggests fates both SSPCs differentiated can be considerably flexible dynamic, multiple sources activated to operate as functional progenitors generating chondrocytes and/or osteoblasts. The combined implementation vivo lineage tracing, surface marker-based selection, single-cell analyses, high-resolution situ imaging has strongly improved our diversity developmental reparative subsets, while also unveiling complexity their dynamics, hierarchies, relationships. Albeit incompletely understood at present, findings supporting flexibility possibly plasticity among osteogenic challenge classical dogma single primitive, self-renewing, multipotent driving tissue formation regeneration from apex hierarchical strictly unidirectional differentiation tree. We here review state field newest discoveries origin, identity, during discuss contributions adult SSPC fracture repair, reflect on dynamism relationships precursors lineages. Further directed unraveling heterogeneity capacities SSPCs, well regulatory fate functioning, will offer vital options for clinical translation toward compromised healing regenerative medicine.

Language: Английский

Citations

12
Biologically Relevant Heterogeneity: Metrics and Practical Insights DOI Creative Commons
Albert Gough, Andrew M. Stern, John Maier

et al.

SLAS DISCOVERY, Journal Year: 2017, Volume and Issue: 22(3), P. 213 - 237

Published: Jan. 7, 2017

Heterogeneity is a fundamental property of biological systems at all scales that must be addressed in wide range biomedical applications, including basic research, drug discovery, diagnostics, and the implementation precision medicine. There are number published approaches to characterizing heterogeneity cells vitro tissue sections. However, there no generally accepted for detection quantitation can applied relatively high-throughput workflow. This review perspective emphasizes experimental methods capture multiplexed cell-level data, as well need standard metrics spatial, temporal, population components heterogeneity. A recommendation made adoption set three indices implemented any workflow optimize decision-making process. In addition, pairwise mutual information method suggested an approach spatial features heterogeneity, especially tissue-based imaging. Furthermore, temporal early stages development. Example studies indicate analysis functional phenotypic exploited guide decisions interpretation experiments, design optimal therapeutic strategies individual patients.

Language: Английский

Citations

81
Muscle Stem Cells Exhibit Distinct Clonal Dynamics in Response to Tissue Repair and Homeostatic Aging DOI Creative Commons
Matthew Tierney, Michael J. Stec, Steffen Rulands

et al.

Cell stem cell, Journal Year: 2017, Volume and Issue: 22(1), P. 119 - 127.e3

Published: Dec. 14, 2017

Language: Английский

Citations

76
Contributions of Mammalian Chimeras to Pluripotent Stem Cell Research DOI Creative Commons

Victoria L. Mascetti,

Roger A. Pedersen

Cell stem cell, Journal Year: 2016, Volume and Issue: 19(2), P. 163 - 175

Published: Aug. 1, 2016

Chimeras are widely acknowledged as the gold standard for assessing stem cell pluripotency, based on their capacity to test donor lineage potential in context of an organized, normally developing tissue. Experimental chimeras provide key insights into mammalian developmental mechanisms and offer a resource interrogating fate various pluripotent states. We highlight applications current limitations presented by intra- inter-species consider future contribution field. Despite technical ethical demands experimental chimeras, including human-interspecies they provocative achieving regenerative medicine goals.

Language: Английский

Citations

75
Alternative direct stem cell derivatives defined by stem cell location and graded Wnt signalling DOI
Amy Reilein, David Melamed, Karen Sophia Park

et al.

Nature Cell Biology, Journal Year: 2017, Volume and Issue: 19(5), P. 433 - 444

Published: April 17, 2017

Language: Английский

Citations

66
Dynamic heterogeneity as a strategy of stem cell self-renewal DOI Open Access
Philip Greulich, Benjamin D. Simons

Proceedings of the National Academy of Sciences, Journal Year: 2016, Volume and Issue: 113(27), P. 7509 - 7514

Published: June 16, 2016

Significance In many tissues, such as intestine and skin, cells are constantly turned over throughout life. To replenish that lost, new generated by stem cells, which divide differentiate to maintain tissue in a steady state. The mechanisms allow achieve perfect self-renewal promise fundamental insights into processes leading diseased states. Efforts define strategies of cell have placed emphasis on models progress one way through differentiation hierarchy. Here, we show different paradigm, transfer reversibly between states primed for renewal or poised differentiation, offers viable robust mechanism self-renewal.

Language: Английский

Citations

62
De novo mutations, genetic mosaicism and human disease DOI Creative Commons
Mohiuddin Mohiuddin, R. Frank Kooy, Christopher E. Pearson

et al.

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 26, 2022

Mosaicism—the existence of genetically distinct populations cells in a particular organism—is an important cause genetic disease. Mosaicism can appear as de novo DNA mutations, epigenetic alterations DNA, and chromosomal abnormalities. Neurodevelopmental or neuropsychiatric diseases, including autism—often arise by mutations that usually not present either the parents. De might occur early parental germline, during embryonic, fetal development, and/or post-natally, through ageing life. Mutation timing could lead to mutation burden less than heterozygosity approaching homozygosity. Developmental somatic attainment will affect load distribution throughout body. In this review, we discuss spanning from germ lineage (all ages), post-zygotic, fetal, post-natal events, aging death. These factors determine tissue specific which The disease threshold gene any be define.

Language: Английский

Citations

38
Human spermatogonial stem cells and their niche in male (in)fertility: novel concepts from single-cell RNA-sequencing DOI Creative Commons
Sara Di Persio, Nina Neuhaus

Human Reproduction, Journal Year: 2022, Volume and Issue: 38(1), P. 1 - 13

Published: Nov. 21, 2022

Abstract The amount of single-cell RNA-sequencing (scRNA-seq) data produced in the field human male reproduction has steadily increased. Transcriptional profiles thousands testicular cells have been generated covering neonatal, prepubertal, pubertal and adult period as well different types infertility; latter include non-obstructive azoospermia, cryptozoospermia, Klinefelter syndrome azoospermia factor deletions. In this review, we provide an overview transcriptional changes subpopulations during postnatal development cases infertility. Moreover, review novel concepts regarding existence spermatogonial somatic cell subtypes their crosstalk corresponding marker genes to facilitate identification. We discuss potential clinical implications scRNA-seq findings, need for spatial information necessity corroborate findings by exploring other levels regulation, including at epigenetic or protein level.

Language: Английский

Citations

32
Deep sequencing as a probe of normal stem cell fate and preneoplasia in human epidermis DOI Creative Commons
Benjamin D. Simons

Proceedings of the National Academy of Sciences, Journal Year: 2015, Volume and Issue: 113(1), P. 128 - 133

Published: Dec. 22, 2015

Significance The sporadic acquisition of somatic DNA mutation confers a hereditary label that can be used to trace the fate behavior cells in normal and diseased states. Applied human tumor samples, deep sequencing methods have revealed landscape mutations identified repertoire genes implicated cancer. By adapting statistical analyze lineage tracing data transgenic animal models, we use example epidermis show how provide quantitative insight into self-renewal properties tissues serve as platform define rare nonneutral field transformations.

Language: Английский

Citations

59