Tissue Stem Cells and ageing - Pekka Katajisto
Tissue resident stem cells (a.k.a. adult stem cells) renew and repair our tissues. However, generation of new stem cells via self-renewal and their differentiation into functional cells must be carefully balanced. During ageing, multiple types of alterations directly in stem cells or in their tissue neighbourhood can disturb this balance. Our laboratory studies both stem cell intrinsic and extrinsic mechanisms altering tissue renewal capacity, and how such mechanisms ultimately result in ageing.
Asymmetric cell division
At least some stem cells can divide asymmetrically to generate a new stem cell and a differentiating cell in a predetermined fashion. This raises the question of the nature of factors that are asymmetrically segregated between the two daughter cells, and how ageing affects this segregation. We are developing methods to analyse whether stem cells apportion their organelles selectively upon asymmetric divisions, and studying the role of related mechanisms in tissue repair.
Cellular metabolism and cell fate
Stem cells have distinct metabolic features. However, whether cellular metabolism facilitates other cellular programmes (self-renewal and differentiation), or whether certain metabolic features can initiate and maintain stemness remains unknown. We study how external cues, such as nutrition, can change stem cell metabolism, and influence their function. Moreover, as mitochondria are a central organelle to cellular metabolism, we probe the hierarchy between cellular metabolism and cell fate by concentrating on the specific case of asymmetric cell division.
Impact of the stem cell niche on ageing
Stem cells are surrounded, nurtured, and protected by their stem cell Niche. The Niche consists of the neighbouring cells, and extracellular matrix, that jointly inform stem cells on the state of the tissue and organismal physiology. Consequently, age-associated changes in the niche can dramatically impact stem cell activity. We study multiple novel ageing associated niche factors, and develop strategies to increase renewal and repair of old tissues by targeting such stem cell extrinsic factors. Our studies span niche features such as cell-cell contacts, tissue topology, and ECM composition.
Notum produced by Paneth cells attenuates regeneration of aged intestinal epithelium.
Pentinmikko N, Iqbal S, Mana M, Andersson S, Cognetta AB 3rd, Suciu RM, Roper J, Luopajärvi K, Markelin E, Gopalakrishnan S, Smolander OP, Naranjo S, Saarinen T, Juuti A, Pietiläinen K, Auvinen P, Ristimäki A, Gupta N, Tammela T, Jacks T, Sabatini DM, Cravatt BF, Yilmaz ÖH, Katajisto P. Nature. 2019 Jul;571(7765):398-402. doi: 10.1038/s41586-019-1383-0. Epub 2019 Jul 10
A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma.
Tammela T, Sanchez-Rivera FJ, Cetinbas NM, Wu K, Joshi NS, Helenius K, Park Y, Azimi R, Kerper NR, Wesselhoeft RA, Gu X, Schmidt L, Cornwall-Brady M, Yilmaz ÖH, Xue W, Katajisto P, Bhutkar A, Jacks T. Nature. 2017 May 18;545(7654):355-359. doi: 10.1038/nature22334. Epub 2017 May 10.
- Fellowship for postdoctoral scholars from SSMF (Svenska Sällskapet för Medicinsk Forskning). (Sandra Scharaw)
- Centre of Excellence in Stem Cell Metabolism - Metastem