Pontin is essential for murine hematopoietic stem cell survival. by Bereshchenko, O, Mancini, E, Luciani, L, Gambardella, A, Riccardi, C, Nerlov, C

“…Competitive repopulation experiments showed that this included the loss of hematopoietic stem cells through apopotosis. Pontin is, therefore, essential for the function of both embryonic pluripotent cells and adult hematopoietic stem cells.…”

Lineage-biased hematopoietic stem cells are regulated by distinct niches by Pinho, S, Marchand, T, Yang, E, Wei, Q, Nerlov, C, Frenette, P

“…The spatial localization of hematopoietic stem cells (HSCs) in the bone marrow (BM) remains controversial, with some studies suggesting that they are maintained in homogeneously distributed niches while others have suggested the contributions of distinct niche structures. …”

Hierarchically related lineage-restricted fates by multipotent hematopoietic stem cells by Carrelha, C, Meng, Y, Kettyle, L, Luis, T, Norfo, R, Alcolea, V, Boukarabila, H, Grasso, F, Gambardella, A, Grover, A, Grover, A, Högstrand, K, Lord, A, Sanjuan-Pla, A, Woll, P, Nerlov, C, Jacobsen, S

DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction. by Bröske, A, Vockentanz, L, Kharazi, S, Huska, MR, Mancini, E, Scheller, M, Kuhl, C, Enns, A, Prinz, M, Jaenisch, R, Nerlov, C, Leutz, A, Andrade-Navarro, M, Jacobsen, SE, Rosenbauer, F

“…Here, we show that alternative functional programs of hematopoietic stem cells (HSCs) are governed by gradual differences in methylation levels. …”

Alternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cells by Carrelha, J, Mazzi, S, Winroth, A, Hagemann-Jensen, M, Ziegenhain, C, Högstrand, K, Seki, M, Brennan, MS, Lehander, M, Wu, B, Meng, Y, Markljung, E, Norfo, R, Ishida, H, Belander Strålin, K, Grasso, F, Simoglou Karali, C, Aliouat, A, Hillen, A, Chari, E, Siletti, K, Thongjuea, S, Mead, AJ, Linnarsson, S, Nerlov, C, Jacobsen, SEW

Activation of the canonical Wnt pathway leads to loss of hematopoietic stem cell repopulation and multilineage differentiation block. by Kirstetter, P, Anderson, K, Porse, B, Jacobsen, SE, Nerlov, C

“…Wnt signaling increases hematopoietic stem cell self-renewal and is activated in both myeloid and lymphoid malignancies, indicating involvement in both normal and malignant hematopoiesis. …”

Niche-mediated depletion of the normal hematopoietic stem cell reservoir by Flt3-ITD–induced myeloproliferation by Mead, A, Neo, W, Barkas, N, Matsuoka, S, Giustacchini, A, Facchini, R, Thongjuea, S, Jamieson, L, Booth, C, Fordham, N, Di Genua, C, Atkinson, D, Chowdhury, O, Repapi, E, Gray, N, Kharazi, S, Clark, S, Bouriez, T, Woll, P, Suda, T, Nerlov, C, Jacobsen, S

“…Although previous studies suggested that the expression of FMS-like tyrosine kinase 3 (Flt3) initiates downstream of mouse hematopoietic stem cells (HSCs), FLT3 internal tandem duplications (FLT3 ITDs) have recently been suggested to intrinsically suppress HSCs. …”

Single cell RNA sequencing reveals molecular and functional platelet bias of aged hematopoietic stem cells by Nerlov, C, Grover, A, Giustacchini, A, Gambardella, A, Macaulay, I, Mead, A, Jacobsen, S, Sanjuan-Pla, A, Thongjuea, S, Carrelha, J, Mancini, E, Luis, T

“…Aged hematopoietic stem cells (HSCs) generate more myeloid cells and fewer lymphoid cells compared to young HSCs, contributing to decreased adaptive immunity in aged individuals. …”

Perivascular niche cells sense thrombocytopenia and activate hematopoietic stem cells in an IL-1 dependent manner by Luis, TC, Barkas, N, Carrelha, J, Giustacchini, A, Mazzi, S, Norfo, R, Wu, B, Aliouat, A, Guerrero, JA, Rodriguez-Meira, A, Bouriez-Jones, T, Macaulay, IC, Jasztal, M, Zhu, G, Ni, H, Robson, MJ, Blakely, RD, Mead, AJ, Nerlov, C, Ghevaert, C, Jacobsen, SEW

“…Hematopoietic stem cells (HSCs) residing in specialized niches in the bone marrow are responsible for the balanced output of multiple short-lived blood cell lineages in steady-state and in response to different challenges. …”

Hematopoietic stem cell expansion precedes the generation of committed myeloid leukemia-initiating cells in C/EBPalpha mutant AML. by Bereshchenko, O, Mancini, E, Moore, S, Bilbao, D, Månsson, R, Luc, S, Grover, A, Jacobsen, SE, Bryder, D, Nerlov, C

“…We find that C-terminal C/EBPalpha mutations increase the proliferation of long-term hematopoietic stem cells (LT-HSCs) in a cell-intrinsic manner and override normal HSC homeostasis, leading to expansion of premalignant HSCs. …”

Loss of endothelial membrane KIT ligand affects systemic KIT ligand levels but not bone marrow hematopoietic stem cells by Matsuoka, S, Facchini, R, Luis, TC, Carrelha, J, Woll, PS, Mizukami, T, Wu, B, Boukarabila, H, Buono, M, Norfo, R, Arai, F, Suda, T, Mead, AJ, Nerlov, C, Jacobsen, SEW

“…A critical regulatory role of hematopoietic stem cell (HSC) vascular niches in the bone marrow has been implicated to occur through endothelial niche cell expression of KIT ligand. …”

Cell-intrinsic depletion of Aml1-ETO-expressing pre-leukemic hematopoietic stem cells by K-Ras activating mutation. by Di Genua, C, Norfo, R, Rodriguez-Meira, A, Wen, W, Drissen, R, Booth, C, Povinelli, B, Repapi, E, Gray, N, Carrelha, J, Kettyle, L, Jamieson, L, Neo, W, Thongjuea, S, Nerlov, C, Mead, A

“…However, activated K-Ras had a marked detrimental effect on Aml1-ETO-expressing hematopoietic stem cells, leading to loss of both phenotypic and functional hematopoietic stem cells. …”

Dicer is selectively important for the earliest stages of erythroid development. by Buza-Vidas, N, Cismasiu, V, Moore, S, Mead, A, Woll, P, Lutteropp, M, Melchiori, L, Luc, S, Bouriez-Jones, T, Atkinson, D, O'Carroll, D, Jacobsen, SE, Nerlov, C

“…MicroRNAs (miRs) are involved in many aspects of normal and malignant hematopoiesis, including hematopoietic stem cell (HSC) self-renewal, proliferation, and terminal differentiation. …”

Kit ligand has a critical role in mouse yolk sac and aorta-gonad-mesonephros hematopoiesis by Azzoni, E, Frontera, V, McGrath, K, Harman, J, Carrelha, J, Nerlov, C, Palis, J, Jacobsen, S, De Bruijn, M

“…This EMP defect causes a dramatic decrease in fetal liver erythroid cells prior to the onset of hematopoietic stem cell (HSC)-derived erythropoiesis, and a reduction in tissue-resident macrophages. …”

Molecular and cellular effects of oncogene cooperation in a genetically accurate AML mouse model. by Reckzeh, K, Bereshchenko, O, Mead, A, Rehn, M, Kharazi, S, Jacobsen, SE, Nerlov, C, Cammenga, J

“…These cellular changes are accompanied by an upregulation of hematopoietic stem cell and STAT5 target genes. By gene expression analysis in premalignant populations, we further show a role of FLT3 ITD in activating genes involved in survival/transformation and chemoresistance. …”

Molecular and cellular effects of oncogene cooperation in a genetically accurate AML mouse model. by Reckzeh, K, Bereshchenko, O, Mead, A, Rehn, M, Kharazi, S, Jacobsen, SE, Nerlov, C, Cammenga, J

“…These cellular changes are accompanied by an upregulation of hematopoietic stem cell and STAT5 target genes. By gene expression analysis in premalignant populations, we further show a role of FLT3 ITD in activating genes involved in survival/transformation and chemoresistance. …”

Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate. by Grover, A, Mancini, E, Moore, S, Mead, A, Atkinson, D, Rasmussen, K, O'Carroll, D, Jacobsen, SE, Nerlov, C

“…This induces erythroid lineage bias at all lineage bifurcations known to exist between hematopoietic stem cells (HSCs) and committed erythroid progenitors, leading to increased erythroid and decreased myeloid HSC output. …”

Inflammatory signals directly instruct PU.1 in HSCs via TNF by Etzrodt, M, Ahmed, N, Hoppe, P, Loeffler, D, Skylaki, S, Hilsenbeck, O, Kokkaliaris, K, Kaltenbach, H, Stelling, J, Nerlov, C, Schroeder, T

“…The molecular mechanisms governing the transition from hematopoietic stem cells (HSCs) to lineage-committed progenitors remain poorly understood. …”

The molecular signature of MDS stem cells supports a stem-cell origin of 5q myelodysplastic syndromes. by Nilsson, L, Edén, P, Olsson, E, Månsson, R, Astrand-Grundström, I, Strömbeck, B, Theilgaard-Mönch, K, Anderson, K, Hast, R, Hellström-Lindberg, E, Samuelsson, J, Bergh, G, Nerlov, C, Johansson, B, Sigvardsson, M, Borg, A, Jacobsen, SE

“…Global gene expression profiling of highly purified 5q-deleted CD34+CD38(-)Thy1+ cells in 5q- myelodysplastic syndromes (MDSs) supported that they might originate from and outcompete normal CD34+CD38(-)Thy1+ hematopoietic stem cells. Few but distinct differences in gene expression distinguished MDS and normal stem cells. …”

Micro-environmental sensing by bone marrow stroma identifies IL-6 and TGFβ1 as regulators of hematopoietic ageing by Valletta, S, Thomas, A, Meng, Y, Ren, X, Drissen, R, Sengül, H, Di Genua, C, Nerlov, C

“…How intrinsic changes to the hematopoietic stem cells (HSCs), an altered microenvironment and systemic factors contribute to this process is not fully understood. …”