Florian Group

Stem Cell Aging

Understanding alterations of aged somatic stem cells and improve the regeneration of tissues

Aging is the first risk factor for most diseases and we believe that understanding the biology of stem cell aging will be critical to enhance stem cell function and preserve their regenerative capacity over time. Our mission is to end the threat of age-related diseases and promote longevity
M. Carolina Florian
Group Leader, Regenerative Medicine Program of IDIBELL
Group Leader of P-CMRC

Lab focus – Understanding epigenetic regulators of the aging process

Somatic stem cells have the ability to regenerate tissues over time. This capacity declines with age, disrupting tissue maintenance. Many age-related diseases, including cancer and sarcopenia, are likely consequence of stem cell dysfunction. Understanding how stem cells age and identifying intervention strategies to maintain stem cell function and regenerative capacity is thus likely to lead to new therapeutic approaches for maintaining our health as we age. Our lab uses mouse models to explore the biology of stem cell function and regeneration and to identify mechanisms of age-related stem cell dysfunction. Our focus is on epigenetic alterations that can be pharmacologically targeted and on the interactions between stem cells and the niche. Based on our findings we have identified intervention strategies to improve the regenerative capacity of aged stem cells and we have unravelled biological alterations in the stem cell niche that could help our understanding of disease development in the elderly.

Why it matters

Interventions that promote stem cell health are likely to provide new avenues to prolong human tissue health and to treat or prevent a wide range of age-related diseases. Coupling fundamental insight into stem cell biology to the exploration of such intervention strategies is likely to be a productive route for the identification of new and promising therapeutic approaches.

News

State of ‘hibernation’ keeps haematopoietic stem cells young
Niches in the bone marrow protect haematopoietic stem cells from ageing

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Inhibition of Cdc42 activity extends murine lifespan
Cdc42 is a small RhoGTPase regulating multiple functions in eukaryotic cells…

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La inteligencia artificial, nueva aliada contra la leucemia
La leucemia mieloide aguda es un tipo de cáncer de la sangre muy agresivo. Afecta 10 veces……

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One PhD Fellowship INPhINIT with La Caixa Foundation available in my team
Details about eligibility criteria, how to apply and the project are available at this link:

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Keywords

Stem Cells, Aging, Regenerative Medicine, Epigenetics, Chromatin, Hematopoietic Stem Cell, Bone Marrow Niche

Publications

Sacma M, Pospiech J, Bogeska R, de Back W, Mallm JP, Sakk V, Soller K, Marka G, Vollmer A, Karns R, Cabezas-Wallscheid N, Trumpp A, Mendez-Ferrer S, Milsom MD, Mulaw M, Geiger H, Florian MC (2019) Haematopoietic stem cells in perisinusoidal niches are protected from ageing. Nat Cell Biol in press
Grigoryan A, Guidi N, Senger K, Liehr T, Soller K, Marka G, Vollmer A, Markaki Y, Leonhardt H, Buske C, Lipka DB, Plass C, Zheng Y, Mulaw MA, Geiger H, Florian MC. (2018) LaminA/C regulates epigenetic and chromatin architecture changes upon aging of hematopoietic stem cells. Genome Biol 19(1):189.
Florian MC*, Sacma M, Klose M, Knudson L, Soller K, Marka G, Nattamai KJ, Sakk V, Zheng Y, Mulaw MA, Glauche I, Geiger H* (2018) Aging alters the epigenetic asymmetry of HSC division. DOI 10.1371/journal.pbio.2003389. PLOS Biology *corresponding authors
Florian MC, Klenk J, Marka G, Soller K, Kiryakos H, Peter R, Herbolsheimer F, Rothenbacher D, Denkinger M, Geiger H (2017) Expression and activity of the small RhoGTPase Cdc42 in blood cells of older adults are associated with age and cardiovascular disease. J Gerontol A Biol Sci Med Sci
Florian MC, Nattamai KJ, Dorr K, Marka G, Uberle B, Vas V, Eckl C, Andra I, Schiemann M, Oostendorp RA, Scharffetter-Kochanek K, Kestler HA, Zheng Y, Geiger H (2013) A canonical to non-canonical Wnt signalling switch in haematopoietic stem-cell ageing. Nature 503: 392-6
Current Members
Past Members
Current Members
Eva Mejía Ramírez de Arellano
Research Assistant
Research project: Upon aging the epigenetic and chromatin architecture of hematopoietic stem cells is altered together with a decreased in their regenerative capacity. Understanding how the chromatin and epigenetic architecture is changing might offer new therapeutic strategies for improving tissue regeneration of aged stem cells.
Francesca Matteini
Post Doc
Research project: Stem cell activity tightly depends on their supporting microenvironment. Understanding how the stem cell niche is changing upon aging will shed new light on the mechanisms of stem cell/niche interaction and tissue regeneration upon aging and disease.
Barbara Walter
PhD student
Research project: Acute myeloid leukaemia incidence increases exponentially with aging, while survival outcome for older patients is extremely poor. Epigenetic alterations in aged stem cells are supposed to be involved in disease development and represent possible new therapeutic targets.
Past Members
Ani Grigoryan
Johannes Pospiech
Noelle J. Ali
Polina Zjablovskaja

M. Carolina Florian
Group Leader, Regenerative Medicine Program of IDIBELL
Group Leader of P-CMRC

mflorian@idibell.cat

Dr. M. Carolina Florian holds a PhD from the University of Milano (Italy). She pursued postdoctoral training at the Institute of Molecular Medicine in Ulm University (Germany) from 2009 to 2015. In 2016, she was awarded an Emmy Noether Grant from the German Research Foundation (DFG) dedicated to outstanding early-career researchers. This grant supported the establishment of her independent research team on Epigenetics of Stem Cell Aging. In 2018, she was appointed as group leader at CMRB (Spain).

Her research in the past 5 years strongly challenged the concept that aging is an irreversible process and showed that it is possible to pharmacologically target the aged-dependent alteration of stem cell epigenetic polarity and functionally rejuvenate aged HSCs in vivo. Somatic stem cells are central for tissue homeostasis and regeneration. Their age-dependent functional decline constitutes a hallmark of tissue attrition upon aging, eventually limiting health-span and lifespan. Dr. Florian’s work is committed to further grow the understanding of alterations affecting aged somatic stem cells and she is investigating changes of the epigenetic architecture that drive stem cell aging, to improve tissue attrition with age or even to prevent aging-associated diseases.

Eva Mejía Ramírez de Arellano
Research Assistant
emejia@idibell.cat

Dr. Eva Mejía obtained her Bachelor´s degree in Biochemistry at the Universidad Autónoma de Madrid in 2001. She performed her PhD studies in Molecular Biology at the Centro de Investigaciones Biológicas-CSIC in Madrid from 2002 to 2006, studying the molecular mechanisms of replication fork blockage in the yeast Schizosaccharomyces pombe under the direction of Dr. Pablo Hernández Valenzuela. She demonstrated the role of the protein Sap1 in replication fork blockage at the rDNA in S. pombe.

After that, Dr. Mejía moved to the USA to work as a Research Associate in Professor Paul Russell’s lab at the Scripps Research Institute in La Jolla, California from 2007 to 2011. She studied the genetics and the molecular mechanisms in S. pombe involved in Replication Checkpoint Maintenance and Double Strand Break Repair. Her results have contributed to the understanding of Brc1 role in Double-Strand Break (DSB) repair during S-phase, and also, the role of the complex Ku80-Ku70 in DSB repair through Homologous Recombination together with Ctp1.

In 2011 she moved back to Spain to work as a Postdoctoral Researcher at Professor Ferran Azorín’s lab where she studied the function of CENP-B homolog in S. pombe in its role in chromatin organization using ChIP-Seq.

Dr. Mejía joined the CMRB in April of 2013 as a Research Assistant.

Francesca Matteini
Post Doc
fmatteini@idibell.cat

Francesca Matteini obtained her bachelor degree in biological sciences in 2012 from the University of Florence. During this period she studied the effect of cosmic radiation on hereditary material after its exposure to extraterrestrial environment.

She followed her studies obtaining her master degree in cellular and molecular biology at the University of Florence in 2015. During her master’s internship she worked on the characterization of the autocrine and paracrine action of bone marrow-derived Mesenchymal Stromal Cells, focusing on role of sphingolipids. From October 2015 to February 2019 Francesca performed her PhD in human biology and medical genetics at the Sapienza University of Rome. During her PhD Francesca studied the role of the Poly(ADP-ribose)polymerase 1 (PARP1) in the transcriptional regulation of MyoD target genes.

Francesca joined the Center of Regenerative Medicine in Barcelona (CMRB) in March 2019 first with an Erasmus-Unipharma Graduates scholarship and then as postdoctoral researcher in Dr. Carolina Florian’s group, focusing on the role of the bone marrow niche in the regulation of HSCs function upon aging.

Barbara Walter
PhD Student

Barbara recently joined Carolina’s group as PhD student. She’s interested in epigenetics and alteration of the bone marrow microenvironment during acute myeloid leukaemia in the elderly. Focusing on finding serotype independent, protein-based vaccines against Streptococcus pneumoniae, she did her Bachelor in genetics at the University of Greifswald. She acquired her Master’s degree in molecular and cell biology at the Free University of Berlin. Her master thesis was focused on characterizing a novel Cre-DreERT2 mouse strain to get more insights into Multiple Myeloma.