Understanding the regulation of vertebrate hematopoiesis and blood disorders – big lessons from a small fish

Robertson, Anne L.; Avagyan, Serine; Gansner, John M.; Zon, Leonard I.

doi:10.1002/1873-3468.12415

Cited by 35 publications

(27 citation statements)

References 163 publications

(207 reference statements)

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“…We do not intend here to provide detailed overview of non-human models, as this extensive topic has been reviewed recently by us and by others Kim et al, 2014;Ciau-Uitz et al, 2016;Kauts et al, 2016;Robertson et al, 2016;Crisan and Dzierzak, 2016). Owing to the high accessibility of model organisms for experimentation and the genetic variability and rarity of human embryonic material, the analysis of human haematopoietic development has lagged behind these wellestablished experimental models and for a long time was limited to immunohistological and in vitro studies.…”

Section: Introductionmentioning

confidence: 99%

Human haematopoietic stem cell development: from the embryo to the dish

et al. 2017

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Haematopoietic stem cells (HSCs) emerge during embryogenesis and give rise to the adult haematopoietic system. Understanding how early haematopoietic development occurs is of fundamental importance for basic biology and medical sciences, but our knowledge is still limited compared with what we know of adult HSCs and their microenvironment. This is particularly true for human haematopoiesis, and is reflected in our current inability to recapitulate the development of HSCs from pluripotent stem cells in vitro. In this Review, we discuss what is known of human haematopoietic development: the anatomical sites at which it occurs, the different temporal waves of haematopoiesis, the emergence of the first HSCs and the signalling landscape of the haematopoietic niche. We also discuss the extent to which in vitro differentiation of human pluripotent stem cells recapitulates bona fide human developmental haematopoiesis, and outline some future directions in the field.

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Section: Introductionmentioning

confidence: 99%

Human haematopoietic stem cell development: from the embryo to the dish

et al. 2017

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“…As UFM1 has been shown to be crucial for hematopoiesis (Tatsumi et al, 2011;Zhang et al, 2015;Cai et al, 2015), we then studied the relevance of MRE11 UFMylation in vivo in a zebrafish model using the unique advantages of zebrafish for genetic analysis of hematopoiesis. As in mammals, zebrafish hematopoiesis occurs in two waves: the primitive wave generates a transient population of blood cells, while the second wave generates hematopoietic stem cells (HSCs) by around 30 hours post-fertilization (Robertson et al, 2016). Genetic inactivation of either ufm1, ufl1 or mre11a with CRISPR-Cas9 ( Fig.…”

Section: Ufm1 Pathway Is Essential To Prevent Telomere Instability Anmentioning

confidence: 99%

UFMylation of MRE11 is essential for maintenance of telomere length and hematopoietic stem cell survival

L¹,

Ab²,

Churikov³

et al. 2019

Preprint

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Modification of MRE11 by UFM1 regulates telomere maintenance and cell death in HSCs Scientific categoryUFMylation, telomere maintenance, hematopoietic stem cell survival. AbstractGenetic studies using knockout mouse models provide strong evidence for the essential role of the ubiquitin-like protein UFM1 for hematopoiesis, especially erythroid development, yet its biological roles in this process are largely unknown. Here we have identified a UFL1-dependent UFMylation of the MRE11 nuclease on the K281 and K282 residues. We show that Hela cells lacking the specific UFM1 E3 ligase display severe telomere shortening. We further demonstrate either by deleting UFM1 or by mutating MRE11 UFMylation sites that preventing MRE11 UFMylation impacts its interaction with the telomere protein TRF2. However, the MRE11 function in double-strand-break repair remains intact. We validate these results in vivo by showing that Zebrafish knockouts for the genes ufl1 and ufm1 have shorter telomeres in hematopoietic cells. Here we present UFMylation has a new mechanisms of regulation for telomere length maintenance with a role in hematopoiesis. Cancer", Equipe labellisée. We acknowledge Jean-Hugues Guervilly and Mauro Modesti for discussion, advices and comment, the two students in the lab who helped with this work, Lea Verrier and Leyla Ameur, the CRCM facilities including TrGET, microcopy and FACS, and I Fuentes and PJ Martínez for excellent technical assistance and zebrafish maintenance. Proteomics analyses were supported by the Institut Paoli-Calmettes and the Centre de Recherche en Cancérologie de Marseille. Proteomic analyses were done using the mass spectrometry facility of Marseille Proteomics

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“…4.1a). The earliest hematopoietic cells emerge during the primitive wave, which gives rise to mostly erythroid and myeloid cells arising from the lateral mesoderm during the first 24 h post fertilization (hpf) (equivalent to blood formation in the mammalian yolk sac) (reviewed in Robertson et al (2016)). The final wave gives rise to definitive HSCs that persist into adulthood to maintain hematopoiesis throughout the organism’s life.…”

Section: 1 Introductionmentioning

confidence: 99%

Developmental HSC Microenvironments: Lessons from Zebrafish

Nik

Weinreb

Bowman

2017

Advances in Experimental Medicine and Biology

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Hematopoietic stem cells (HSCs) posses the ability to maintain the blood system of an organism from birth to adulthood. The behavior of HSCs is modulated by its microenvironment. During development, HSCs acquire the instructions to self-renew and differentiate into all blood cell fates by passing through several developmental microenvironments. In this chapter, we discuss the signals and cell types that inform HSC decisions throughout ontogeny with a focus on HSC specification, mobilization, migration, and engraftment.

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Understanding the regulation of vertebrate hematopoiesis and blood disorders – big lessons from a small fish

Cited by 35 publications

References 163 publications

Human haematopoietic stem cell development: from the embryo to the dish

Human haematopoietic stem cell development: from the embryo to the dish

UFMylation of MRE11 is essential for maintenance of telomere length and hematopoietic stem cell survival

Developmental HSC Microenvironments: Lessons from Zebrafish

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