Epigenetic clocks based on tissue DNA methylation analysis have emerged as robust and powerful biomarkers of aging. This technology has allowed scientists to investigate how diseases affect the aging process, to evaluate the effectiveness of therapeutic aging interventions, and to correlate age with overall health among the general public. Today you can even purchase test kits online that enable you to measure your own biological age. However, despite the growing use of epigenetic clocks in research, surprisingly little is known about the aging clock’s cellular underpinnings. For example, it remains unclear whether all cells within a tissue exhibit the same epigenetic age, and whether age-related cellular heterogeneity within a tissue affects the epigenetic clock. This is particularly relevant in regenerative tissues maintained by a hierarchy of stem, progenitor, and differentiated cells, all of which may change their frequencies within a tissue with age. The guests on today’s podcast tackle this important question through analyses of immature and mature cell populations from muscle, blood, and epithelia, using three different epigenetic clocks widely used in the field. They discuss their results, and the implications for the interpretation of existing clocks, and the development of more sensitive and accurate clocks.

Guests
Konrad Hochedlinger, PhD, Massachusetts General Hospital and Harvard Stem Cell Institute, MA, USA

Rebecca Gorelov, PhD, Harvard Medical School, USA

Host
Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
X: @martinperaJAX

Supporting Paper
Dissecting the impact of differentiation stage, replicative history, and cell type composition in epigenetic clocks, Stem Cell Reports

About Stem Cell Reports
Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians.
X: @StemCellReports

About ISSCR
With nearly 5,000 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scientific Advisor

Voice Work
Ben Snitkoff

Those who study neurological diseases and their underlying cellular and molecular mechanisms have a number of scientific models at their disposal. In vivo animal models, particularly those bearing targeted genetic modifications, remain the gold standard, especially when it comes to assessment of behavioral readouts and neurobiological disease mechanisms in vivo. Historically, animal models have been widely used for preclinical validation of drug efficacy and safety.

Increasingly there is a move away from this approach, and human cellular models using induced pluripotent stem cells and their derivatives such as three-dimensional organoid models have recently provided unprecedented genetic and mechanistic insights into disease mechanisms. Human/animal chimeras made by xenografting human cells into the animal brain have unparalleled potential to study human cells in the context of the whole organism. Our guests today review the use of these types of model systems to understand neuropsychiatric diseases, focusing on Alzheimer’s and Parkinson’s disease, epilepsy, Down syndrome, and schizophrenia and provide critical appraisal of the impact of human-rodent xenografting approaches for advancing our understanding of those diseases and brain development.

Host
Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
@martinperaJAX

Guests
Giuseppe Testa, MD, PhD, Università Statale, Human Technopole, and the European Institute of Oncology, Italy

Marlene Pereira, PhD UCB Pharma, Brussels, Belgium

Reinald Shyti, PhD, Human Technopole and the European Institute of Oncology, Italy

Supporting Content
In and out: benchmarking in vitro, in vivo, ex vivo and xenografting approaches for an integrative brain disease modeling pipeline, Stem Cell Reports

About Stem Cell Reports
Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians.
Twitter: @StemCellReports

About ISSCR
With nearly 5,000 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scientific Advisor

Voice Work
Ben Snitkoff

This episode of The Stem Cell Report will discuss the process of directing stem cells to acquire the proper identity, an essential step in the development of effective and durable cell replacement therapies. Specifically, we will talk about the process of directing cells into a ventral mesencephalic dopaminergic fate for treating Parkinson’s disease.

Guests
Agnete Kirkeby is an Associate Professor in the Department of Neuroscience at the University of Copenhagen, a Principal Investigator with the Novo Nordisk Foundation Center for Stem Cell Medicine renew, and a Principal Investigator at the Wallenberg Center for Molecular Medicine at Lund University. Professor Kirkeby led the preclinical development of a stem cell-based therapy for Parkinson’s Disease which was approved for a first-in-human clinical trial in Sweden. Agnete also co-chairs the ISSCR 2024 Annual Meeting Program Committee, the group responsible for planning the upcoming meeting this July in Hamburg, Germany.

Pedro Rifes received his PhD from the Universidade de Lisboa in Portugal and was a postdoctoral scholar in the Kirkeby Laboratory. He served as an Adjunct Assistant Professor at the University of Copenhagen and is currently a Project Manager at Bioneer A/S, a Danish specialty Contract Research Organization. Connect with him on LinkedIn.

Host
Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
@martinperaJAX

Supporting Content
Paper link: Forced LMX1A expression induces dorsal neural lolfates and disrupts patterning of human embryonic stem cells into ventral midbrain dopaminergic neurons, Stem Cell Reports

About Stem Cell Reports
Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. X: @StemCellReports

About ISSCR
With nearly 5,000 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health.

ISSCR Staff
Keith Alm, Chief Executive Officer
Yvonne Fisher, Managing Editor, Stem Cell Reports
Kym Kilbourne, Director of Media and Strategic Communications
Jack Mosher, Scientific Advisor

Voice Work
Ben Snitkoff