Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 15293810

Stem cells: cross-talk and developmental programs.

Jaime Imitola·Kook In Park·Yang D Teng·Sahar Nisim·Mahesh Lachyankar·Jitka Ourednik·Franz-Josef Mueller·Rene Yiou·Anthony Atala·Richard L Sidman·Mark Tuszynski·Samia J Khoury·Evan Y Snyder
View original source ↗Export metadata ↓

Abstract

The thesis advanced in this essay is that stem cells-particularly those in the nervous system-are components in a series of inborn 'programs' that not only ensure normal development, but persist throughout life so as to maintain homeostasis in the face of perturbations-both small and great. These programs encode what has come to be called 'plasticity'. The stem cell is one of the repositories of this plasticity. This review examines the evidence that interaction between the neural stem cell (as a prototypical somatic stem cell) and the developing or injured brain is a dynamic, complex, ongoing reciprocal set of interactions where both entities are constantly in flux. We suggest that this interaction can be viewed almost from a 'systems biology' vantage point. We further advance the notion that clones of exogenous stem cells in transplantation paradigms may not only be viewed for their therapeutic potential, but also as biological tools for 'interrogating' the normal or abnormal central nervous system environment, indicating what salient cues (among the many present) are actually guiding the expression of these 'programs'; in other words, using the stem cell as a 'reporter cell'. Based on this type of analysis, we suggest some of the relevant molecular pathways responsible for this 'cross-talk' which, in turn, lead to proliferation, migration, cell genesis, trophic support, protection, guidance, detoxification, rescue, etc. This type of developmental insight, we propose, is required for the development of therapeutic strategies for neurodegenerative disease and other nervous system afflictions in humans. Understanding the relevant molecular pathways of stem cell repair phenotype should be a priority, in our view, for the entire stem cell field.

Explore related subjects

BrainCell DifferentiationHomeostasisHumansNeuronal PlasticityOrganogenesisSignal TransductionStem CellsWound HealingJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.Review

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Jaime Imitola, Kook In Park, Yang D Teng, Sahar Nisim, Mahesh Lachyankar, Jitka Ourednik, Franz-Josef Mueller, Rene Yiou, Anthony Atala, Richard L Sidman, Mark Tuszynski, Samia J Khoury, Evan Y Snyder. 2004-05-29. Stem cells: cross-talk and developmental programs.. https://doi.org/10.1098/rstb.2004.1474

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2026

A MAGIBU-based model for pediatric and juvenile CNS tumors: an in-house epigenetic decision-support framework compared with online DNA methylation classifiers.

Background: DNA methylation profiling is a tool that provides key support for central nervous system (CNS) tumor classification. However, diagnostically ambiguous pediatric cases may result in discordant outputs across classifiers. We developed MAGIBU, a cross-platform, projection-based framework that embeds individual methylomes into a fixed CNS reference landscape, ranking diagnostic entities by local epigenetic proximity to support clinician-led integrative diagnosis. Methods: As a proof-of-concept, we evaluated MAGIBU in eight morphologically challenging pediatric/juvenile CNS tumors with unresolved diagnoses after institutional and central pathology review. To establish a benchmark in the absence of a definitive histopathological ground truth, a consensus epigenetic reference was defined a priori for cases showing concordant results between the Heidelberg CNS Tumor Methylation Classifier and Methylscape Analysis. Comparisons were also performed with Epigenomic Digital Pathology (EpiDiP). To validate MAGIBU beyond this discovery cohort, performance was assessed at the family level across the CNS methylation spectrum (n = 678, 28 methylation families), on non-array platforms (whole-genome bisulfite sequencing and Oxford Nanopore), and in a focused analysis of the low-grade glioma and diffuse midline glioma compartment across four independent cohorts (n = 670). Results: In the discovery cohort, MAGIBU achieved high concordance with the consensus reference (Cohen's κ = 0.855), outperforming EpiDiP (κ = 0.278), which frequently placed low-grade tumors in proximity to higher-grade reference regions. Conclusions: MAGIBU provides a stable, quantitative differential diagnosis framework that mitigates the limitations of rigid categorical assignments. By leveraging a distance-based proximity metric, it offers a transparent decision-support tool that integrates effectively with clinical, radiological, and molecular data. While performance is inherently dependent on reference atlas composition, MAGIBU represents a robust complementary approach for the diagnostic workup of ambiguous CNS tumors.

Brain↗
PubMed2021

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

Brain↗
PubMed2005

Simultaneous measurement of saturation and relaxation in human brain by repetitive magnetization transfer pulses.

Magnetization transfer (MT) by equidistant pulse trains can be described as being analogous to progressive partial saturation, where 'direct' saturation of water is amplified by MT contributions that are dependent on macromolecular content and differential saturation. This concept was applied to study the transition to steady state in the human brain using similar MT-pulses as in imaging. Up to 41 bell-shaped MT-pulses of 12 ms duration were applied at frequency offsets between 0.5 and 15 kHz with flip angles between 1080 and 1440 degrees . Central white and parietal gray matter was studied in human subjects using STEAM for localized read-out (TE = 30 ms, TM = 13.7 ms). The apparent degree of saturation, delta(app), and the longitudinal relaxation of the water pool during the pulse repetition period (PR) were fitted to the transient behavior after signal correction for cerebro-spinal fluid. PR was varied between 15 and 100 ms to assess the PR-dependence of the fitted parameters. The MT-term in delta(app) exceeded the direct saturation and attained its maximum at PR > or = 100 ms. The macromolecular pool was only partially saturated by a single MT-pulse. The offset may be increased to 2.5 kHz to reduce direct saturation without sacrificing MT in white matter. The estimated relaxation rates (1.04 +/- 0.11 s(-1) in WM; 0.76 +/- 0.13 s(-1) in GM) were faster than are commonly observed at 1.5 T. The apparent saturation is a measure for MT that is not confounded by relaxation. To maximize MT in brain tissue, MT-pulses should be applied at PR = 100 ms or longer. At shorter PR, a larger steady state saturation is obtained at the cost of increased contributions from direct saturation. Since this accelerates the convergence, PR should be decreased to reach the steady state within a specified time. A faster transition can always be achieved at a reduced frequency offset via increased direct saturation.

Brain↗