Cytometry in the brain: studying differentiation to diagnostic applications in brain disease and regeneration therapy

Abstract

During brain development, a population of uniform embryonic cells migrates and differentiates into a large number of neural phenotypes - origin of the enormous complexity of the adult nervous system. Processes of cell proliferation, differentiation and programmed death of no longer required cells, do not occur only during embryogenesis, but are also maintained during adulthood and are affected in neurodegenerative and neuropsychiatric disease states. As neurogenesis is an endogenous response to brain injury, visible as proliferation (of to this moment silent stem or progenitor cells), its further stimulation can present a treatment strategy in addition to stem cell transfer for cell regeneration therapy. Concise techniques for studying such events in vitro and in vivo permit understanding of underlying mechanisms. Detection of subtle physiological alterations in brain cell proliferation and neurogenesis can be explored, that occur during environmental stimulation, exercise and ageing. Here, we have collected achievements in the field of basic research on applications of cytometry, including automated imaging for quantification of morphological or fluorescence-based parameters in cell cultures, towards imaging of three-dimensional brain architecture together with DNA content and proliferation data. Multi-parameter and more recently in vivo flow cytometry procedures, have been developed for quantification of phenotypic diversity and cell processes that occur during brain development as well as in adulthood, with importance for therapeutic approaches.

miR‐30c and semaphorin 3A determine adult neurogenesis by regulating proliferation and differentiation of stem cells in the subventricular zones of mouse

“…Although adult neurogenesis in mammals is restricted to a few regions, it contributes a certain degree of plasticity to the adult brain . Evidence suggests that the capacity for adult neurogenesis is determined by the proliferative and differentiated states of adult stem cells . A correlation between differentiation and cell‐cycle lengthening has been reported in several cell lineages in vitro and in vivo .…”

In silico molecular cytogenetics: a bioinformatic approach to prioritization of candidate genes and copy number variations for basic and clinical genome research

“…For instance, numerous brain diseases are associated with SGV (CIN/GIN) manifested as aneuploidy or structural genome variations [ 14 , 18 , 37 , 42 - 48 ]. These data have served as a basis for speculations about diagnostic applications of SGV analysis in brain disease and regeneration therapy [ 49 ]. Still, the idea remains undeveloped and further theoretical input is needed.…”

Aptamer for imaging and therapeutic targeting of brain tumor glioblastoma

“…As near-infrared quantum-dots could be used for in vivo imaging of glioblastoma tissue (54), such approach should be also feasible for aptamerbased fluorescence imaging in vivo. Aptamers shall also gain importance in pathology analysis of tumor samples, i.e., analysis in intact brain tissue (55). Here image cytometry is the adequate technique for aptamer-based quantification of tumor antigenes.…”